興奮性毒性是由於麩胺酸的過量累積而導致麩胺酸受體過度活化。星狀膠細胞會表現代謝型麩胺酸受體（mGluR）並介導在三連突觸處的麩胺酸的釋放與回收，以避免神經細胞過度興奮。星狀膠細胞上的mGluR活化後下游的傳導信號會促進脂質介質14,15-環氧二十碳三烯酸（14,15-EET）的合成，而經由抑制可溶性環氧化物水解酶（sEH），則使得14,15-環氧二十碳三烯酸的降解被阻斷，進而提供了神經保護作用。過去的研究顯示抑制sEH在許多腦部疾病模型中提供神經保護作用，然而，如何透過抑制sEH調節麩胺酸的神經興奮性毒性的機制目前尚未清楚。為了研究抑制sEH和14,15-EET抵抗神經興奮性毒性的潛在機制，本論文使用三種大鼠腦皮質初代細胞培養系統，分別為富含神經元細胞（NE）、星狀膠細胞-神經元混和性細胞（GN）、以及純化的星狀膠細胞培養系統。我的研究發現，在GN混和性神經細胞中，sEH抑制劑AUDA以及14,15-EET均可減少N-甲基-D-天門冬胺酸（NMDA）導致的神經突（neurite）損傷、細胞死亡和細胞內鈣離子流入，而在NE細胞系統卻是呈現相反的現象。14,15-EET和AUDA的抗神經興奮性毒性保護作用是透過降低sEH酵素活性，而不是調控酵素的表現。mGluR5拮抗劑MPEP可阻斷仰賴神經膠細胞所提供的14,15-EET和AUDA的抗神經興奮性毒性保護作用以及抵抗神經蛋白的損害。以麩胺酸刺激純化初代星狀膠細胞的實驗發現14,15-EET/AUDA可減少c-Jun N端激酶1（JNK1）的磷酸化，其中14,15-EET的作用是依賴mGluR5所介導，進而促進星狀膠細胞的存活。我們也釐清了MPEP對於mGluR5所介導的JNK1活化和14,15-EET抑制JNK1活化的效果。在GN混和性細胞中，14,15-EET/AUDA能回復被NMDA所降低之透過麩胺酸轉運蛋白（GLT-1）所介導的麩胺酸回收，此作用並非透過快速直接活化轉運蛋白，且此作用為mGluR5所介導。此保護作用是來自於對被NMDA破壞的表現GLT-1之神經周圍星狀膠細胞突起（PAP）的保護作用，回復其密度以及寬度，此作用亦為mGluR5所介導，同時不影響GLT-1蛋白的表現。14,15-EET/AUDA所維護的PAP型態也保護了PSD95標定的興奮性神經突觸。此外，基因抑制（knockdown）sEH表現亦可減弱NMDA神經興奮毒性，此保護作用亦透過mGluR5及GLT-1調控。活體動物實驗中，使用大鼠興奮性腦損傷模式驗證了經由腦室注射AUDA短效治療可降低神經興奮毒性紅藻胺酸（KA）誘導的海馬迴亞區中神經細胞損傷、sEH表現及神經細胞周圍表現GLT-1的星狀膠細胞損傷。其中海馬迴CA3亞區中對於表現GLT-1的星狀膠細胞細胞突的保護與神經突的保護二者之間呈現線性正相關。在小鼠動物模式中，鼻腔給予另一種sEH抑制劑TPPU的亞慢性治療和遺傳剔除sEH小鼠（Ephx2-KO），不僅能維持海馬迴CA3亞區中錐狀細胞層及透明層中表現GLT-1的PAP，並且可以減少星狀膠細胞增生。此外，周邊給予sEH抑制劑亦能緩解在動物模式中NMDA誘發的紋狀體破壞及免疫細胞反應，包含微膠細胞活化及單核細胞浸潤。上述研究結論顯示，14,15-EET透過mGluR5介導促進星狀膠細胞存活，維持星狀膠細胞表現GLT-1的突起結構的完整性，進而維持麩胺酸恆定。此外，sEH抑制劑亦能減少興奮型腦損傷後免疫細胞的活化及浸潤。以上機制共同提供抗興奮性神經毒性的神經保護效果。本研究所獲得之資訊，或許可以對於sEH在興奮性腦損傷與疾病提供潛在的機制與抑制sEH可應用的治療方向。

Excitotoxicity is triggered by an excessive accumulation of glutamate and resulting in overactivation of glutamate receptors which leads to cell death. Astrocytes express metabotropic glutamate receptors (mGluR) which mediate glutamate release and uptake at tripartite synapses and avoid neuronal hyperexcitation. Astrocytic mGluR downstream signaling activates the synthesis of lipid mediator 14,15-epoxyeicosatrienoic acid (14,15-EET), and the degradation of which is blocked by the inhibition of soluble epoxide hydrolase (sEH) and provides neuroprotection. It has been shown that sEH inhibition is neuroprotective in various brain disease models, however, it remains unclear how sEH inhibition regulates glutamate excitotoxicity. In order investigate the cellular mechanism of sEH inhibition and 14,15-EET against excitotoxicity, we used three in vitro primary rat cortical culture systems, including neuron-enriched (NE), astrocyte-enriched glia-neuron mix (GN), and purified astrocytes. We found that sEH inhibitor 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) and 14,15-EET both attenuated N-methyl-D-aspartate (NMDA)-induced neurite damage, cell death, and intracellular calcium influx in astrocyte-enriched GN mix cultures, while there was opposite effect in NE cultures. The protective effect of AUDA came through the decrease of sEH enzyme activity, not via enzyme expression. mGluR5 antagonist 2-methyl-6-(phenylethynyl) pyridine (MPEP) blocked the astrocyte-dependent protective effects of 14,15-EET and AUDA against excitotoxicity and neuronal protein damage. Using glutamate-stimulated primary astrocytes, we confirmed that 14,15-EET/AUDA reduced c-Jun N-terminal kinase 1 (JNK1) phosphorylation, in which the 14,15-EET effect was mGluR5-dependent, and promoted astrocyte survival. We also clarified the effect of MPEP on mGluR5-mediated JNK1 activation and 14,15-EET-inhibited JNK1 activation. In GN mix cultures, 14,15-EET/AUDA restored NMDA-decreased glutamate transporter-1 (GLT-1)-mediated glutamate uptake capacity without acutely direct activation of the transporters, which was also mGuR5-mediated. This protection came with the recovery of the NMDA-disrupted GLT-1 expressing perineuronal astrocyte process (PAP) density and breadth, which was mGluR5-mediated, while the GLT-1 protein expression remained unchanged. The 14,15-EET/AUDA-preserved PAP morphology also protected PSD95-labeled excitatory synapses. Besides, Knockdown of sEH expression also attenuated NMDA neurotoxicity in mGluR5- and GLT-1-dependent manners. In vivo studies validated that acute intracerebroventricular administrated AUDA reduced excitotoxic kainic acid (KA)-induced neuronal damage, sEH induction, and GLT-1-expressing perineuronal astrocytes damage in hippocampus subregions in rat excitotoxic brain injury model. In hippocampal CA3, this GLT-1+ process preservation was linear positive correlated with the neurite protection. Subchronic intranasal delivery of another sEH inhibitor, TPPU, and genetic deletion of sEH (Ephx2-KO) not only preserved GLT-1-expressing PAPs in hippocampal CA3 subregion stratum pyramidale and stratum lucidum but also reduced astrogliosis in KA-injected mice. Furthermore, peripheral delivery of sEH inhibitor also showed amelioration of striatal damage and immune cell response, including microglia activation and monocyte infiltration in NMDA-induced brain injury model. In conclusion, 14,15-EET mediates mGluR5-dependent anti-excitotoxicity by protecting astrocyte survival and process integrity to maintain glutamate homeostasis. In addition, sEH inhibitor also reduces immune cell activation and infiltration after excitotoxic brain injury. The above mechanisms all together provide neuroprotection, which may implicate a potential application of sEH inhibition in treating excitotoxic brain injury and diseases.

Contents
誌謝.....................................I
Contents.................................III
List of Figures..........................IV
Abbreviations............................VI
中文摘要.................................VII
Abstract.................................IX

Chapter 1. Introduction..................1
Chapter 2. Materials & Methods...........12
Chapter 3. Results.......................34
Part I...................................35
Part II..................................47
Chapter 4. Discussion....................49
Part I...................................50
Part II..................................59
Chapter 5. Conclusion & Perspectives.....61
Chapter 6. References....................63
Chapter 7. Figures.......................75

List of Figures

Fig. 1 Differential composition of rat primary neuronal cultures...................................................76
Fig. 2 14,15-EET and sEH inhibitor treatments attenuated NMDA- induced neurotoxicity in glia-neuron mix cultures....77
Fig. 3 14,15-EET and sEH inhibitor treatments did not attenuate NMDA-induced neurotoxicity in neuron-enriched cultures...................................................79
Fig. 4 Neuronal excitation determined by Fura-2 calcium imaging in GN mix and NE cultures treated with 14,15-EET........................................................80
Fig. 5 Gene expression profile and total EETs level in GN mix and NE cultures treated with sEH inhibitor.................82
Fig. 6 Effects of mGluR5 antagonist on NMDA neurotoxicity and sEH inhibition/14,15-EET–mediated anti-excitotoxicity in GN mix cultures...............................................83
Fig. 7 Effects of mGluR5 antagonist on 14,15-EET–preserved neuronal protein expression under NMDA neurotoxic insult in GN mix cultures............................................84
Fig. 8 14,15-EET and AUDA attenuated glutamate-induced JNK1 activation and cell death in primary cultured astrocytes...85
Fig. 9 AMPA receptor antagonist and prolonged MPEP treatment did not affect glutamate-induced JNK1 activation in astrocyte cultures...................................................87
Fig.10 GLT-1 inhibition blocked the anti-excitotoxic effect of 14,15-EET and sEH inhibition in GN mix cultures.........88
Fig.11 GLT-1 inhibition blocked the effect of 14,15-EET/sEH inhibition– preserved glutamate homeostasis under excitotoxicity in GN mix cultures..........................89
Fig.12 mGluR5 antagonist and GLT-1 inhibition blocked the anti-excitotoxic effect of sEH knockdown in GN mix cultures...................................................90
Fig.13 14,15-EET attenuated glutamate-induced astrocyte process damage without affecting GLT-1 expression..........91
Fig.14 Lower magnification images and representative Airyscan images of perineuronal astrocyte processes in GN mix cultures...................................................92
Fig.15 NMDA-induced disruption of GLT-1-expressing perineuronal astrocyte processes was attenuated by both sEH inhibition and 14,15-EET in GN mix cultures................93
Fig.16 Intracerebroventricular injection of sEH inhibitor attenuated the neuronal damage and sEH expression in hippocampal subregions of KA-injected rats.................95
Fig.17 Central application of sEH inhibitor decreased the loss of GLT-1+ astrocyte processes in hippocampal CA3 subregions of KA-injected rats.............................97
Fig.18 The effect of central sEH inhibition on neurite damage and GLT-1+ astrocyte processes in hippocampal CA3 subregions of KA-injected rats........................................99
Fig.19 Subchronic intranasal delivery of sEH inhibitor and genetic deletion of Ephx2 both ameliorated KA-induced loss of GLT-1+ astrocyte processes in mouse hippocampal CA3.......100
Fig.20 Peripheral delivery of sEH inhibitor ameliorated NMDA-induced striatal damage in Thy1-GFP mice..................101
Fig.21 sEH inhibitor attenuated neuronal damage in NMDA-injected Thy1-GFP mice....................................102
Fig.22 Peripheral sEH inhibitor treatment attenuated microglia activation and monocyte infiltration in NMDA-injected CX3CR1-GFP;CCR2-RFP bitransgenic mice ...........103
Fig.23 The proposed mechanism of 14,15-EET/sEH inhibition-mediated neuron-astrocyte interaction for neuroprotection against excitotoxic brain injury..........................104

Aronica, E., Gorter, J. A., Ijlst-Keizers, H., Rozemuller, A. J., Yankaya, B., Leenstra, S., & Troost, D. (2003). Expression and functional role of mGluR3 and mGluR5 in human astrocytes and glioma cells: opposite regulation of glutamate transporter proteins. Eur J Neurosci, 17(10), 2106-2118.
Auladell, C., de Lemos, L., Verdaguer, E., Ettcheto, M., Busquets, O., Lazarowski, A., Beas-Zarate, C., Olloquequi, J., Folch, J., & Camins, A. (2017). Role of JNK isoforms in the kainic acid experimental model of epilepsy and neurodegeneration. Front Biosci (Landmark Ed), 22, 795-814.
Avignone, E., Ulmann, L., Levavasseur, F., Rassendren, F., & Audinat, E. (2008). Status epilepticus induces a particular microglial activation state characterized by enhanced purinergic signaling. J Neurosci, 28(37), 9133-9144.
Ayata, C., Ayata, G., Hara, H., Matthews, R. T., Beal, M. F., Ferrante, R. J., Endres, M., Kim, A., Christie, R. H., Waeber, C., Huang, P. L., Hyman, B. T., & Moskowitz, M. A. (1997). Mechanisms of reduced striatal NMDA excitotoxicity in type I nitric oxide synthase knock-out mice. J Neurosci, 17(18), 6908-6917.
Ben-Ari, Y., & Cossart, R. (2000). Kainate, a double agent that generates seizures: two decades of progress. Trends Neurosci, 23(11), 580-587.
Ben Haim, L., Carrillo-de Sauvage, M. A., Ceyzeriat, K., & Escartin, C. (2015). Elusive roles for reactive astrocytes in neurodegenerative diseases. Front Cell Neurosci, 9, 278.
Bernardinelli, Y., Muller, D., & Nikonenko, I. (2014). Astrocyte-synapse structural plasticity. Neural Plast, 2014, 232105.
Bradley, S. J., & Challiss, R. A. (2012). G protein-coupled receptor signalling in astrocytes in health and disease: a focus on metabotropic glutamate receptors. Biochem Pharmacol, 84(3), 249-259.
Bradley, S. J., Watson, J. M., & Challiss, R. A. (2009). Effects of positive allosteric modulators on single-cell oscillatory Ca2+ signaling initiated by the type 5 metabotropic glutamate receptor. Mol Pharmacol, 76(6), 1302-1313.
Bruno, V., Battaglia, G., Copani, A., Cespedes, V. M., Galindo, M. F., Cena, V., Sanchez-Prieto, J., Gasparini, F., Kuhn, R., Flor, P. J., & Nicoletti, F. (2001). An activity-dependent switch from facilitation to inhibition in the control of excitotoxicity by group I metabotropic glutamate receptors. Eur J Neurosci, 13(8), 1469-1478.
Caviedes, A., Varas-Godoy, M., Lafourcade, C., Sandoval, S., Bravo-Alegria, J., Kaehne, T., Massmann, A., Figueroa, J. P., Nualart, F., & Wyneken, U. (2017). Endothelial Nitric Oxide Synthase Is Present in Dendritic Spines of Neurons in Primary Cultures. Front Cell Neurosci, 11, 180.
Chang, L. H., Lin, H. C., Huang, S. S., Chen, I. C., Chu, K. W., Chih, C. L., Liang, Y. W., Lee, Y. C., Chen, Y. Y., Lee, Y. H., & Lee, I. H. (2018). Blockade of soluble epoxide hydrolase attenuates post-ischemic neuronal hyperexcitation and confers resilience against stroke with TrkB activation. Sci Rep, 8(1), 118.
Chang, Y. C., Kim, H. W., Rapoport, S. I., & Rao, J. S. (2008). Chronic NMDA administration increases neuroinflammatory markers in rat frontal cortex: cross-talk between excitotoxicity and neuroinflammation. Neurochem Res, 33(11), 2318-2323.
Choi, D. W. (1987). Ionic dependence of glutamate neurotoxicity. J Neurosci, 7(2), 369-379.
Choi, D. W., Koh, J. Y., & Peters, S. (1988). Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists. J Neurosci, 8(1), 185-196.
Crupi, R., Impellizzeri, D., & Cuzzocrea, S. (2019). Role of Metabotropic Glutamate Receptors in Neurological Disorders. Front Mol Neurosci, 12, 20.
D'Ascenzo, M., Fellin, T., Terunuma, M., Revilla-Sanchez, R., Meaney, D. F., Auberson, Y. P., Moss, S. J., & Haydon, P. G. (2007). mGluR5 stimulates gliotransmission in the nucleus accumbens. Proc Natl Acad Sci U S A, 104(6), 1995-2000.
Dal-Cim, T., Martins, W. C., Santos, A. R., & Tasca, C. I. (2011). Guanosine is neuroprotective against oxygen/glucose deprivation in hippocampal slices via large conductance Ca(2)+-activated K+ channels, phosphatidilinositol-3 kinase/protein kinase B pathway activation and glutamate uptake. Neuroscience, 183, 212-220.
Davis, C. M., Liu, X., & Alkayed, N. J. (2017). Cytochrome P450 eicosanoids in cerebrovascular function and disease. Pharmacol Ther, 179, 31-46.
de Lemos, L., Junyent, F., Camins, A., Castro-Torres, R. D., Folch, J., Olloquequi, J., Beas-Zarate, C., Verdaguer, E., & Auladell, C. (2018). Neuroprotective Effects of the Absence of JNK1 or JNK3 Isoforms on Kainic Acid-Induced Temporal Lobe Epilepsy-Like Symptoms. Mol Neurobiol, 55(5), 4437-4452.
Deshmane, S. L., Kremlev, S., Amini, S., & Sawaya, B. E. (2009). Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interferon Cytokine Res, 29(6), 313-326.
Dhanasekaran, D. N., & Reddy, E. P. (2008). JNK signaling in apoptosis. Oncogene, 27(48), 6245-6251.
Doria, J. G., Silva, F. R., de Souza, J. M., Vieira, L. B., Carvalho, T. G., Reis, H. J., Pereira, G. S., Dobransky, T., & Ribeiro, F. M. (2013). Metabotropic glutamate receptor 5 positive allosteric modulators are neuroprotective in a mouse model of Huntington's disease. Br J Pharmacol, 169(4), 909-921.
EnayetAllah, A. E., Luria, A., Luo, B., Tsai, H. J., Sura, P., Hammock, B. D., & Grant, D. F. (2008). Opposite regulation of cholesterol levels by the phosphatase and hydrolase domains of soluble epoxide hydrolase. J Biol Chem, 283(52), 36592-36598.
Evstratova, A., & Toth, K. (2014). Information processing and synaptic plasticity at hippocampal mossy fiber terminals. Front Cell Neurosci, 8, 28.
Filosa, J. A., & Iddings, J. A. (2013). Astrocyte regulation of cerebral vascular tone. Am J Physiol Heart Circ Physiol, 305(5), H609-619.
Fornage, M., Lee, C. R., Doris, P. A., Bray, M. S., Heiss, G., Zeldin, D. C., & Boerwinkle, E. (2005). The soluble epoxide hydrolase gene harbors sequence variation associated with susceptibility to and protection from incident ischemic stroke. Hum Mol Genet, 14(19), 2829-2837.
Gauthier, K. M., Deeter, C., Krishna, U. M., Reddy, Y. K., Bondlela, M., Falck, J. R., & Campbell, W. B. (2002). 14,15-Epoxyeicosa-5(Z)-enoic acid: a selective epoxyeicosatrienoic acid antagonist that inhibits endothelium-dependent hyperpolarization and relaxation in coronary arteries. Circ Res, 90(9), 1028-1036.
Geurts, J. J., Wolswijk, G., Bo, L., van der Valk, P., Polman, C. H., Troost, D., & Aronica, E. (2003). Altered expression patterns of group I and II metabotropic glutamate receptors in multiple sclerosis. Brain, 126(Pt 8), 1755-1766.
Graeber, M. B., Li, W., & Rodriguez, M. L. (2011). Role of microglia in CNS inflammation. FEBS Lett, 585(23), 3798-3805.
Grewer, C., Gameiro, A., Zhang, Z., Tao, Z., Braams, S., & Rauen, T. (2008). Glutamate forward and reverse transport: from molecular mechanism to transporter-mediated release after ischemia. IUBMB Life, 60(9), 609-619.
Hansson, E., Ronnback, L., Persson, L. I., Lowenthal, A., Noppe, M., Alling, C., & Karlsson, B. (1984). Cellular composition of primary cultures from cerebral cortex, striatum, hippocampus, brainstem and cerebellum. Brain Res, 300(1), 9-18.
Hardingham, G. E., & Bading, H. (2010). Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders. Nat Rev Neurosci, 11(10), 682-696.
Hardingham, G. E., Fukunaga, Y., & Bading, H. (2002). Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways. Nat Neurosci, 5(5), 405-414.
Hernandez-Jimenez, M., Martinez-Lopez, D., Gabande-Rodriguez, E., Martin-Segura, A., Lizasoain, I., Ledesma, M. D., Dotti, C. G., & Moro, M. A. (2016). Seladin-1/DHCR24 Is Neuroprotective by Associating EAAT2 Glutamate Transporter to Lipid Rafts in Experimental Stroke. Stroke, 47(1), 206-213.
Hoshi, A., Tsunoda, A., Yamamoto, T., Tada, M., Kakita, A., & Ugawa, Y. (2018). Altered expression of glutamate transporter-1 and water channel protein aquaporin-4 in human temporal cortex with Alzheimer's disease. Neuropathol Appl Neurobiol, 44(6), 628-638.
Hou, H. H., Hammock, B. D., Su, K. H., Morisseau, C., Kou, Y. R., Imaoka, S., Oguro, A., Shyue, S. K., Zhao, J. F., & Lee, T. S. (2012). N-terminal domain of soluble epoxide hydrolase negatively regulates the VEGF-mediated activation of endothelial nitric oxide synthase. Cardiovasc Res, 93(1), 120-129.
Huang, H. J., Wang, Y. T., Lin, H. C., Lee, Y. H., & Lin, A. M. (2018). Soluble Epoxide Hydrolase Inhibition Attenuates MPTP-Induced Neurotoxicity in the Nigrostriatal Dopaminergic System: Involvement of alpha-Synuclein Aggregation and ER Stress. Mol Neurobiol, 55(1), 138-144.
Hung, C. C., Lin, C. H., Chang, H., Wang, C. Y., Lin, S. H., Hsu, P. C., Sun, Y. Y., Lin, T. N., Shie, F. S., Kao, L. S., Chou, C. M., & Lee, Y. H. (2016). Astrocytic GAP43 Induced by the TLR4/NF-kappaB/STAT3 Axis Attenuates Astrogliosis-Mediated Microglial Activation and Neurotoxicity. J Neurosci, 36(6), 2027-2043.
Hung, Y. W., Hung, S. W., Wu, Y. C., Wong, L. K., Lai, M. T., Shih, Y. H., Lee, T. S., & Lin, Y. Y. (2015). Soluble epoxide hydrolase activity regulates inflammatory responses and seizure generation in two mouse models of temporal lobe epilepsy. Brain, Behav, Immun, 43, 118-129.
Ibanez, I., Diez-Guerra, F. J., Gimenez, C., & Zafra, F. (2016). Activity dependent internalization of the glutamate transporter GLT-1 mediated by beta-arrestin 1 and ubiquitination. Neuropharmacology, 107, 376-386.
Iliff, J. J., & Alkayed, N. J. (2009). Soluble Epoxide Hydrolase Inhibition: Targeting Multiple Mechanisms of Ischemic Brain Injury with a Single Agent. Future Neurol, 4(2), 179-199.
Imig, J. D. (2012). Epoxides and soluble epoxide hydrolase in cardiovascular physiology. Physiol Rev, 92(1), 101-130.
Imig, J. D., & Hammock, B. D. (2009). Soluble epoxide hydrolase as a therapeutic target for cardiovascular diseases. Nat Rev Drug Discov, 8(10), 794-805.
Inceoglu, B., Zolkowska, D., Yoo, H. J., Wagner, K. M., Yang, J., Hackett, E., Hwang, S. H., Lee, K. S., Rogawski, M. A., Morisseau, C., & Hammock, B. D. (2013). Epoxy fatty acids and inhibition of the soluble epoxide hydrolase selectively modulate GABA mediated neurotransmission to delay onset of seizures. PLoS One, 8(12), e80922.
Jung, S., Aliberti, J., Graemmel, P., Sunshine, M. J., Kreutzberg, G. W., Sher, A., & Littman, D. R. (2000). Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol Cell Biol, 20(11), 4106-4114.
Kobayashi, E., Nakano, M., Kubota, K., Himuro, N., Mizoguchi, S., Chikenji, T., Otani, M., Mizue, Y., Nagaishi, K., & Fujimiya, M. (2018). Activated forms of astrocytes with higher GLT-1 expression are associated with cognitive normal subjects with Alzheimer pathology in human brain. Sci Rep, 8(1), 1712.
Koehler, R. C., Roman, R. J., & Harder, D. R. (2009). Astrocytes and the regulation of cerebral blood flow. Trends Neurosci, 32(3), 160-169.
Koerner, I. P., Jacks, R., DeBarber, A. E., Koop, D., Mao, P., Grant, D. F., & Alkayed, N. J. (2007). Polymorphisms in the human soluble epoxide hydrolase gene EPHX2 linked to neuronal survival after ischemic injury. J Neurosci, 27(17), 4642-4649.
Kundu, S., Roome, T., Bhattacharjee, A., Carnevale, K. A., Yakubenko, V. P., Zhang, R., Hwang, S. H., Hammock, B. D., & Cathcart, M. K. (2013). Metabolic products of soluble epoxide hydrolase are essential for monocyte chemotaxis to MCP-1 in vitro and in vivo. J Lipid Res, 54(2), 436-447.
Lavialle, M., Aumann, G., Anlauf, E., Prols, F., Arpin, M., & Derouiche, A. (2011). Structural plasticity of perisynaptic astrocyte processes involves ezrin and metabotropic glutamate receptors. Proc Natl Acad Sci U S A, 108(31), 12915-12919.
Li, L., Li, N., Pang, W., Zhang, X., Hammock, B. D., Ai, D., & Zhu, Y. (2014). Opposite effects of gene deficiency and pharmacological inhibition of soluble epoxide hydrolase on cardiac fibrosis. PLoS One, 9(4), e94092.
Liddelow, S. A., & Barres, B. A. (2017). Reactive Astrocytes: Production, Function, and Therapeutic Potential. Immunity, 46(6), 957-967.
Lin, C. H., Juan, S. H., Wang, C. Y., Sun, Y. Y., Chou, C. M., Chang, S. F., Hu, S. Y., Lee, W. S., & Lee, Y. H. (2008). Neuronal activity enhances aryl hydrocarbon receptor-mediated gene expression and dioxin neurotoxicity in cortical neurons. J Neurochem, 104(5), 1415-1429.
Liu, M., & Alkayed, N. J. (2005). Hypoxic preconditioning and tolerance via hypoxia inducible factor (HIF) 1alpha-linked induction of P450 2C11 epoxygenase in astrocytes. J Cereb Blood Flow Metab, 25(8), 939-948.
Liu, M., Zhu, Q., Wu, J., Yu, X., Hu, M., Xie, X., Yang, Z., Yang, J., Feng, Y. Q., & Yue, J. (2017). Glutamate affects the production of epoxyeicosanoids within the brain: The up-regulation of brain CYP2J through the MAPK-CREB signaling pathway. Toxicology, 381, 31-38.
Ma, D., Tao, B., Warashina, S., Kotani, S., Lu, L., Kaplamadzhiev, D. B., Mori, Y., Tonchev, A. B., & Yamashima, T. (2007). Expression of free fatty acid receptor GPR40 in the central nervous system of adult monkeys. Neurosci Res, 58(4), 394-401.
Ma, J., Zhang, L., Han, W., Shen, T., Ma, C., Liu, Y., Nie, X., Liu, M., Ran, Y., & Zhu, D. (2012). Activation of JNK/c-Jun is required for the proliferation, survival, and angiogenesis induced by EET in pulmonary artery endothelial cells. J Lipid Res, 53(6), 1093-1105.
MacVicar, B. A., & Newman, E. A. (2015). Astrocyte regulation of blood flow in the brain. Cold Spring Harb Perspect Biol, 7(5), a020388.
Mahmoud, S., Gharagozloo, M., Simard, C., & Gris, D. (2019). Astrocytes Maintain Glutamate Homeostasis in the CNS by Controlling the Balance between Glutamate Uptake and Release. Cells, 8(2), E184.
Malherbe, P., Kratochwil, N., Zenner, M. T., Piussi, J., Diener, C., Kratzeisen, C., Fischer, C., & Porter, R. H. (2003). Mutational analysis and molecular modeling of the binding pocket of the metabotropic glutamate 5 receptor negative modulator 2-methyl-6-(phenylethynyl)-pyridine. Mol Pharmacol, 64(4), 823-832.
Mark, L. P., Prost, R. W., Ulmer, J. L., Smith, M. M., Daniels, D. L., Strottmann, J. M., Brown, W. D., & Hacein-Bey, L. (2001). Pictorial review of glutamate excitotoxicity: fundamental concepts for neuroimaging. AJNR Am J Neuroradiol, 22(10), 1813-1824.
Marowsky, A., Burgener, J., Falck, J. R., Fritschy, J. M., & Arand, M. (2009). Distribution of soluble and microsomal epoxide hydrolase in the mouse brain and its contribution to cerebral epoxyeicosatrienoic acid metabolism. Neuroscience, 163(2), 646-661.
Morisseau, C., & Hammock, B. D. (2013). Impact of soluble epoxide hydrolase and epoxyeicosanoids on human health. Annu Rev Pharmacol Toxicol, 53, 37-58.
Morisseau, C., Inceoglu, B., Schmelzer, K., Tsai, H. J., Jinks, S. L., Hegedus, C. M., & Hammock, B. D. (2010). Naturally occurring monoepoxides of eicosapentaenoic acid and docosahexaenoic acid are bioactive antihyperalgesic lipids. J Lipid Res, 51(12), 3481-3490.
Mule, N. K., Orjuela Leon, A. C., Falck, J. R., Arand, M., & Marowsky, A. (2017). 11,12 -Epoxyeicosatrienoic acid (11,12 EET) reduces excitability and excitatory transmission in the hippocampus. Neuropharmacology, 123, 310-321.
Nakajima, K., Yamamoto, S., Kohsaka, S., & Kurihara, T. (2008). Neuronal stimulation leading to upregulation of glutamate transporter-1 (GLT-1) in rat microglia in vitro. Neurosci Lett, 436(3), 331-334.
Newman, J. W., Morisseau, C., Harris, T. R., & Hammock, B. D. (2003). The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme with novel lipid phosphate phosphatase activity. Proc Natl Acad Sci U S A, 100(4), 1558-1563.
Niswender, C. M., & Conn, P. J. (2010). Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol, 50, 295-322.
Olney, J. W. (1969). Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science, 164(3880), 719-721.
Panatier, A., & Robitaille, R. (2016). Astrocytic mGluR5 and the tripartite synapse. Neuroscience, 323, 29-34.
Park, S. K., Herrnreiter, A., Pfister, S. L., Gauthier, K. M., Falck, B. A., Falck, J. R., & Campbell, W. B. (2018). GPR40 is a low-affinity epoxyeicosatrienoic acid receptor in vascular cells. J Biol Chem, 293(27), 10675-10691.
Perez-Alvarez, A., Navarrete, M., Covelo, A., Martin, E. D., & Araque, A. (2014). Structural and functional plasticity of astrocyte processes and dendritic spine interactions. J Neurosci, 34(38), 12738-12744.
Qu, Y., Liu, Y., Zhu, Y., Chen, L., Sun, W., & Zhu, Y. (2017). Epoxyeicosatrienoic Acid Inhibits the Apoptosis of Cerebral Microvascular Smooth Muscle Cells by Oxygen Glucose Deprivation via Targeting the JNK/c-Jun and mTOR Signaling Pathways. Mol Cells, 40(11), 837-846.
Reiner, A., & Levitz, J. (2018). Glutamatergic Signaling in the Central Nervous System: Ionotropic and Metabotropic Receptors in Concert. Neuron, 98(6), 1080-1098.
Ren, Q., Ma, M., Ishima, T., Morisseau, C., Yang, J., Wagner, K. M., Zhang, J. C., Yang, C., Yao, W., Dong, C., Han, M., Hammock, B. D., & Hashimoto, K. (2016). Gene deficiency and pharmacological inhibition of soluble epoxide hydrolase confers resilience to repeated social defeat stress. Proc Natl Acad Sci U S A, 113(13), E1944-1952.
Reus, G. Z., Abelaira, H. M., Tuon, T., Titus, S. E., Ignacio, Z. M., Rodrigues, A. L., & Quevedo, J. (2016). Glutamatergic NMDA Receptor as Therapeutic Target for Depression. Adv Protein Chem Struct Biol, 103, 169-202.
Rojo, A. I., Innamorato, N. G., Martin-Moreno, A. M., De Ceballos, M. L., Yamamoto, M., & Cuadrado, A. (2010). Nrf2 regulates microglial dynamics and neuroinflammation in experimental Parkinson's disease. Glia, 58(5), 588-598.
Rose, C. R., Felix, L., Zeug, A., Dietrich, D., Reiner, A., & Henneberger, C. (2017). Astroglial Glutamate Signaling and Uptake in the Hippocampus. Front Mol Neurosci, 10, 451.
Rossi, D., Brambilla, L., Valori, C. F., Roncoroni, C., Crugnola, A., Yokota, T., Bredesen, D. E., & Volterra, A. (2008). Focal degeneration of astrocytes in amyotrophic lateral sclerosis. Cell Death Differ, 15(11), 1691-1700.
Sakers, K., Lake, A. M., Khazanchi, R., Ouwenga, R., Vasek, M. J., Dani, A., & Dougherty, J. D. (2017). Astrocytes locally translate transcripts in their peripheral processes. Proc Natl Acad Sci U S A, 114(19), E3830-E3838.
Sanna, M. D., Ghelardini, C., & Galeotti, N. (2015). Activation of JNK pathway in spinal astrocytes contributes to acute ultra-low-dose morphine thermal hyperalgesia. Pain, 156(7), 1265-1275.
Sattler, R., & Tymianski, M. (2001). Molecular mechanisms of glutamate receptor-mediated excitotoxic neuronal cell death. Mol Neurobiol, 24(1-3), 107-129.
Schmelzer, K. R., Kubala, L., Newman, J. W., Kim, I. H., Eiserich, J. P., & Hammock, B. D. (2005). Soluble epoxide hydrolase is a therapeutic target for acute inflammation. Proc Natl Acad Sci U S A, 102(28), 9772-9777.
Schousboe, A., Scafidi, S., Bak, L. K., Waagepetersen, H. S., & McKenna, M. C. (2014). Glutamate metabolism in the brain focusing on astrocytes. Adv Neurobiol, 11, 13-30.
Sellers, K. W., Sun, C., Diez-Freire, C., Waki, H., Morisseau, C., Falck, J. R., Hammock, B. D., Paton, J. F., & Raizada, M. K. (2005). Novel mechanism of brain soluble epoxide hydrolase-mediated blood pressure regulation in the spontaneously hypertensive rat. FASEB J, 19(6), 626-628.
Spector, A. A., & Norris, A. W. (2007). Action of epoxyeicosatrienoic acids on cellular function. Am J Physiol Cell Physiol, 292(3), C996-1012.
Spigolon, G., Veronesi, C., Bonny, C., & Vercelli, A. (2010). c-Jun N-terminal kinase signaling pathway in excitotoxic cell death following kainic acid-induced status epilepticus. Eur J Neurosci, 31(7), 1261-1272.
Stagi, M., Gorlovoy, P., Larionov, S., Takahashi, K., & Neumann, H. (2006). Unloading kinesin transported cargoes from the tubulin track via the inflammatory c-Jun N-terminal kinase pathway. FASEB J, 20(14), 2573-2575.
Sura, P., Sura, R., Enayetallah, A. E., & Grant, D. F. (2008). Distribution and expression of soluble epoxide hydrolase in human brain. J Histochem Cytochem, 56(6), 551-559.
Takahashi, K., Foster, J. B., & Lin, C. L. (2015). Glutamate transporter EAAT2: regulation, function, and potential as a therapeutic target for neurological and psychiatric disease. Cell Mol Life Sci, 72(18), 3489-3506.
Takuma, K., Baba, A., & Matsuda, T. (2004). Astrocyte apoptosis: implications for neuroprotection. Prog Neurobiol, 72(2), 111-127.
Terashvili, M., Sarkar, P., Nostrand, M. V., Falck, J. R., & Harder, D. R. (2012). The protective effect of astrocyte-derived 14,15-epoxyeicosatrienoic acid on hydrogen peroxide-induced cell injury in astrocyte-dopaminergic neuronal cell line co-culture. Neuroscience, 223, 68-76.
Tian, D. S., Peng, J., Murugan, M., Feng, L. J., Liu, J. L., Eyo, U. B., Zhou, L. J., Mogilevsky, R., Wang, W., & Wu, L. J. (2017). Chemokine CCL2-CCR2 Signaling Induces Neuronal Cell Death via STAT3 Activation and IL-1beta Production after Status Epilepticus. J Neurosci, 37(33), 7878-7892.
Torres-Platas, S. G., Comeau, S., Rachalski, A., Bo, G. D., Cruceanu, C., Turecki, G., Giros, B., & Mechawar, N. (2014). Morphometric characterization of microglial phenotypes in human cerebral cortex. J Neuroinflammation, 11, 12.
Trabelsi, Y., Amri, M., Becq, H., Molinari, F., & Aniksztejn, L. (2017). The conversion of glutamate by glutamine synthase in neocortical astrocytes from juvenile rat is important to limit glutamate spillover and peri/extrasynaptic activation of NMDA receptors. Glia, 65(2), 401-415.
Ulas, J., Satou, T., Ivins, K. J., Kesslak, J. P., Cotman, C. W., & Balazs, R. (2000). Expression of metabotropic glutamate receptor 5 is increased in astrocytes after kainate-induced epileptic seizures. Glia, 30(4), 352-361.
Umpierre, A. D., West, P. J., White, J. A., & Wilcox, K. S. (2019). Conditional Knockout of mGluR5 from Astrocytes during Epilepsy Development Impairs High-Frequency Glutamate Uptake. J Neurosci, 39(4), 727-742.
Varvel, N. H., Neher, J. J., Bosch, A., Wang, W., Ransohoff, R. M., Miller, R. J., & Dingledine, R. (2016). Infiltrating monocytes promote brain inflammation and exacerbate neuronal damage after status epilepticus. Proc Natl Acad Sci U S A, 113(38), E5665-5674.
Vermeiren, C., Najimi, M., Vanhoutte, N., Tilleux, S., de Hemptinne, I., Maloteaux, J. M., & Hermans, E. (2005). Acute up-regulation of glutamate uptake mediated by mGluR5a in reactive astrocytes. J Neurochem, 94(2), 405-416.
Vezzani, A., Balosso, S., & Ravizza, T. (2008). The role of cytokines in the pathophysiology of epilepsy. Brain Behav Immun, 22(6), 797-803.
Viviani, B., Boraso, M., Marchetti, N., & Marinovich, M. (2014). Perspectives on neuroinflammation and excitotoxicity: a neurotoxic conspiracy? Neurotoxicology, 43, 10-20.
Wang, J. Q., Fibuch, E. E., & Mao, L. (2007). Regulation of mitogen-activated protein kinases by glutamate receptors. J Neurochem, 100(1), 1-11.
Wu, C. H., Shyue, S. K., Hung, T. H., Wen, S., Lin, C. C., Chang, C. F., & Chen, S. F. (2017a). Genetic deletion or pharmacological inhibition of soluble epoxide hydrolase reduces brain damage and attenuates neuroinflammation after intracerebral hemorrhage. J Neuroinflammation, 14(1), 230.
Wu, H. F., Chen, Y. J., Wu, S. Z., Lee, C. W., Chen, I. T., Lee, Y. C., Huang, C. C., Hsing, C. H., Tang, C. W., & Lin, H. C. (2017b). Soluble Epoxide Hydrolase Inhibitor and 14,15-Epoxyeicosatrienoic Acid-Facilitated Long-Term Potentiation through cAMP and CaMKII in the Hippocampus. Neural Plast, 2017, 3467805.
Wu, H. F., Yen, H. J., Huang, C. C., Lee, Y. C., Wu, S. Z., Lee, T. S., & Lin, H. C. (2015). Soluble epoxide hydrolase inhibitor enhances synaptic neurotransmission and plasticity in mouse prefrontal cortex. J Biomed Sci, 22, 94.
Wu, P. C., & Kao, L. S. (2016). Calcium regulation in mouse mesencephalic neurons-Differential roles of Na(+)/Ca(2+) exchanger, mitochondria and endoplasmic reticulum. Cell Calcium, 59(6), 299-311.
Xie, C., Sun, J., Qiao, W., Lu, D., Wei, L., Na, M., Song, Y., Hou, X., & Lin, Z. (2011). Administration of simvastatin after kainic acid-induced status epilepticus restrains chronic temporal lobe epilepsy. PLoS One, 6(9), e24966.
Yang, D., Sun, Y. Y., Bhaumik, S. K., Li, Y., Baumann, J. M., Lin, X., Zhang, Y., Lin, S. H., Dunn, R. S., Liu, C. Y., Shie, F. S., Lee, Y. H., Wills-Karp, M., Chougnet, C. A., Kallapur, S. G., Lewkowich, I. P., Lindquist, D. M., Murali-Krishna, K., & Kuan, C. Y. (2014). Blocking lymphocyte trafficking with FTY720 prevents inflammation-sensitized hypoxic-ischemic brain injury in newborns. J Neurosci, 34(49), 16467-16481.
Yang, Y., Tian, X., Xu, D., Zheng, F., Lu, X., Zhang, Y., Ma, Y., Li, Y., Xu, X., Zhu, B., & Wang, X. (2018). GPR40 modulates epileptic seizure and NMDA receptor function. Sci Adv, 4(10), eaau2357.
Yuan, L., Liu, J., Dong, R., Zhu, J., Tao, C., Zheng, R., & Zhu, S. (2016). 14,15-epoxyeicosatrienoic acid promotes production of BDNF from astrocytes and exerts neuroprotective effects during ischemic injury. Neuropathol Appl Neurobiol, 42(7), 607-620.
Zhang, K., Wang, H., Xu, M., Frank, J. A., & Luo, J. (2018). Role of MCP-1 and CCR2 in ethanol-induced neuroinflammation and neurodegeneration in the developing brain. J Neuroinflammation, 15(1), 197.
Zhang, L., Ding, H., Yan, J., Hui, R., Wang, W., Kissling, G. E., Zeldin, D. C., & Wang, D. W. (2008a). Genetic variation in cytochrome P450 2J2 and soluble epoxide hydrolase and risk of ischemic stroke in a Chinese population. Pharmacogenet Genomics, 18(1), 45-51.
Zhang, W., Koerner, I. P., Noppens, R., Grafe, M., Tsai, H. J., Morisseau, C., Luria, A., Hammock, B. D., Falck, J. R., & Alkayed, N. J. (2007). Soluble epoxide hydrolase: a novel therapeutic target in stroke. J Cereb Blood Flow Metab, 27(12), 1931-1940.
Zhang, W., Otsuka, T., Sugo, N., Ardeshiri, A., Alhadid, Y. K., Iliff, J. J., DeBarber, A. E., Koop, D. R., & Alkayed, N. J. (2008b). Soluble epoxide hydrolase gene deletion is protective against experimental cerebral ischemia. Stroke, 39(7), 2073-2078.
Zheng, S., Eacker, S. M., Hong, S. J., Gronostajski, R. M., Dawson, T. M., & Dawson, V. L. (2010). NMDA-induced neuronal survival is mediated through nuclear factor I-A in mice. J Clin Invest, 120(7), 2446-2456.
Zhou, J., & Sutherland, M. L. (2004). Glutamate transporter cluster formation in astrocytic processes regulates glutamate uptake activity. J Neurosci, 24Aronica, E., Gorter, J. A., Ijlst-Keizers, H., Rozemuller, A. J., Yankaya, B., Leenstra, S., & Troost, D. (2003). Expression and functional role of mGluR3 and mGluR5 in human astrocytes and glioma cells: opposite regulation of glutamate transporter proteins. Eur J Neurosci, 17(10), 2106-2118.
Auladell, C., de Lemos, L., Verdaguer, E., Ettcheto, M., Busquets, O., Lazarowski, A., Beas-Zarate, C., Olloquequi, J., Folch, J., & Camins, A. (2017). Role of JNK isoforms in the kainic acid experimental model of epilepsy and neurodegeneration. Front Biosci (Landmark Ed), 22, 795-814.
Avignone, E., Ulmann, L., Levavasseur, F., Rassendren, F., & Audinat, E. (2008). Status epilepticus induces a particular microglial activation state characterized by enhanced purinergic signaling. J Neurosci, 28(37), 9133-9144.
Ayata, C., Ayata, G., Hara, H., Matthews, R. T., Beal, M. F., Ferrante, R. J., Endres, M., Kim, A., Christie, R. H., Waeber, C., Huang, P. L., Hyman, B. T., & Moskowitz, M. A. (1997). Mechanisms of reduced striatal NMDA excitotoxicity in type I nitric oxide synthase knock-out mice. J Neurosci, 17(18), 6908-6917.
Ben-Ari, Y., & Cossart, R. (2000). Kainate, a double agent that generates seizures: two decades of progress. Trends Neurosci, 23(11), 580-587.
Ben Haim, L., Carrillo-de Sauvage, M. A., Ceyzeriat, K., & Escartin, C. (2015). Elusive roles for reactive astrocytes in neurodegenerative diseases. Front Cell Neurosci, 9, 278.
Bernardinelli, Y., Muller, D., & Nikonenko, I. (2014). Astrocyte-synapse structural plasticity. Neural Plast, 2014, 232105.
Bradley, S. J., & Challiss, R. A. (2012). G protein-coupled receptor signalling in astrocytes in health and disease: a focus on metabotropic glutamate receptors. Biochem Pharmacol, 84(3), 249-259.
Bradley, S. J., Watson, J. M., & Challiss, R. A. (2009). Effects of positive allosteric modulators on single-cell oscillatory Ca2+ signaling initiated by the type 5 metabotropic glutamate receptor. Mol Pharmacol, 76(6), 1302-1313.
Bruno, V., Battaglia, G., Copani, A., Cespedes, V. M., Galindo, M. F., Cena, V., Sanchez-Prieto, J., Gasparini, F., Kuhn, R., Flor, P. J., & Nicoletti, F. (2001). An activity-dependent switch from facilitation to inhibition in the control of excitotoxicity by group I metabotropic glutamate receptors. Eur J Neurosci, 13(8), 1469-1478.
Caviedes, A., Varas-Godoy, M., Lafourcade, C., Sandoval, S., Bravo-Alegria, J., Kaehne, T., Massmann, A., Figueroa, J. P., Nualart, F., & Wyneken, U. (2017). Endothelial Nitric Oxide Synthase Is Present in Dendritic Spines of Neurons in Primary Cultures. Front Cell Neurosci, 11, 180.
Chang, L. H., Lin, H. C., Huang, S. S., Chen, I. C., Chu, K. W., Chih, C. L., Liang, Y. W., Lee, Y. C., Chen, Y. Y., Lee, Y. H., & Lee, I. H. (2018). Blockade of soluble epoxide hydrolase attenuates post-ischemic neuronal hyperexcitation and confers resilience against stroke with TrkB activation. Sci Rep, 8(1), 118.
Chang, Y. C., Kim, H. W., Rapoport, S. I., & Rao, J. S. (2008). Chronic NMDA administration increases neuroinflammatory markers in rat frontal cortex: cross-talk between excitotoxicity and neuroinflammation. Neurochem Res, 33(11), 2318-2323.
Choi, D. W. (1987). Ionic dependence of glutamate neurotoxicity. J Neurosci, 7(2), 369-379.
Choi, D. W., Koh, J. Y., & Peters, S. (1988). Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists. J Neurosci, 8(1), 185-196.
Crupi, R., Impellizzeri, D., & Cuzzocrea, S. (2019). Role of Metabotropic Glutamate Receptors in Neurological Disorders. Front Mol Neurosci, 12, 20.
D'Ascenzo, M., Fellin, T., Terunuma, M., Revilla-Sanchez, R., Meaney, D. F., Auberson, Y. P., Moss, S. J., & Haydon, P. G. (2007). mGluR5 stimulates gliotransmission in the nucleus accumbens. Proc Natl Acad Sci U S A, 104(6), 1995-2000.
Dal-Cim, T., Martins, W. C., Santos, A. R., & Tasca, C. I. (2011). Guanosine is neuroprotective against oxygen/glucose deprivation in hippocampal slices via large conductance Ca(2)+-activated K+ channels, phosphatidilinositol-3 kinase/protein kinase B pathway activation and glutamate uptake. Neuroscience, 183, 212-220.
Davis, C. M., Liu, X., & Alkayed, N. J. (2017). Cytochrome P450 eicosanoids in cerebrovascular function and disease. Pharmacol Ther, 179, 31-46.
de Lemos, L., Junyent, F., Camins, A., Castro-Torres, R. D., Folch, J., Olloquequi, J., Beas-Zarate, C., Verdaguer, E., & Auladell, C. (2018). Neuroprotective Effects of the Absence of JNK1 or JNK3 Isoforms on Kainic Acid-Induced Temporal Lobe Epilepsy-Like Symptoms. Mol Neurobiol, 55(5), 4437-4452.
Deshmane, S. L., Kremlev, S., Amini, S., & Sawaya, B. E. (2009). Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interferon Cytokine Res, 29(6), 313-326.
Dhanasekaran, D. N., & Reddy, E. P. (2008). JNK signaling in apoptosis. Oncogene, 27(48), 6245-6251.
Doria, J. G., Silva, F. R., de Souza, J. M., Vieira, L. B., Carvalho, T. G., Reis, H. J., Pereira, G. S., Dobransky, T., & Ribeiro, F. M. (2013). Metabotropic glutamate receptor 5 positive allosteric modulators are neuroprotective in a mouse model of Huntington's disease. Br J Pharmacol, 169(4), 909-921.
EnayetAllah, A. E., Luria, A., Luo, B., Tsai, H. J., Sura, P., Hammock, B. D., & Grant, D. F. (2008). Opposite regulation of cholesterol levels by the phosphatase and hydrolase domains of soluble epoxide hydrolase. J Biol Chem, 283(52), 36592-36598.
Evstratova, A., & Toth, K. (2014). Information processing and synaptic plasticity at hippocampal mossy fiber terminals. Front Cell Neurosci, 8, 28.
Filosa, J. A., & Iddings, J. A. (2013). Astrocyte regulation of cerebral vascular tone. Am J Physiol Heart Circ Physiol, 305(5), H609-619.
Fornage, M., Lee, C. R., Doris, P. A., Bray, M. S., Heiss, G., Zeldin, D. C., & Boerwinkle, E. (2005). The soluble epoxide hydrolase gene harbors sequence variation associated with susceptibility to and protection from incident ischemic stroke. Hum Mol Genet, 14(19), 2829-2837.
Gauthier, K. M., Deeter, C., Krishna, U. M., Reddy, Y. K., Bondlela, M., Falck, J. R., & Campbell, W. B. (2002). 14,15-Epoxyeicosa-5(Z)-enoic acid: a selective epoxyeicosatrienoic acid antagonist that inhibits endothelium-dependent hyperpolarization and relaxation in coronary arteries. Circ Res, 90(9), 1028-1036.
Geurts, J. J., Wolswijk, G., Bo, L., van der Valk, P., Polman, C. H., Troost, D., & Aronica, E. (2003). Altered expression patterns of group I and II metabotropic glutamate receptors in multiple sclerosis. Brain, 126(Pt 8), 1755-1766.
Graeber, M. B., Li, W., & Rodriguez, M. L. (2011). Role of microglia in CNS inflammation. FEBS Lett, 585(23), 3798-3805.
Grewer, C., Gameiro, A., Zhang, Z., Tao, Z., Braams, S., & Rauen, T. (2008). Glutamate forward and reverse transport: from molecular mechanism to transporter-mediated release after ischemia. IUBMB Life, 60(9), 609-619.
Hansson, E., Ronnback, L., Persson, L. I., Lowenthal, A., Noppe, M., Alling, C., & Karlsson, B. (1984). Cellular composition of primary cultures from cerebral cortex, striatum, hippocampus, brainstem and cerebellum. Brain Res, 300(1), 9-18.
Hardingham, G. E., & Bading, H. (2010). Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders. Nat Rev Neurosci, 11(10), 682-696.
Hardingham, G. E., Fukunaga, Y., & Bading, H. (2002). Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways. Nat Neurosci, 5(5), 405-414.
Hernandez-Jimenez, M., Martinez-Lopez, D., Gabande-Rodriguez, E., Martin-Segura, A., Lizasoain, I., Ledesma, M. D., Dotti, C. G., & Moro, M. A. (2016). Seladin-1/DHCR24 Is Neuroprotective by Associating EAAT2 Glutamate Transporter to Lipid Rafts in Experimental Stroke. Stroke, 47(1), 206-213.
Hoshi, A., Tsunoda, A., Yamamoto, T., Tada, M., Kakita, A., & Ugawa, Y. (2018). Altered expression of glutamate transporter-1 and water channel protein aquaporin-4 in human temporal cortex with Alzheimer's disease. Neuropathol Appl Neurobiol, 44(6), 628-638.
Hou, H. H., Hammock, B. D., Su, K. H., Morisseau, C., Kou, Y. R., Imaoka, S., Oguro, A., Shyue, S. K., Zhao, J. F., & Lee, T. S. (2012). N-terminal domain of soluble epoxide hydrolase negatively regulates the VEGF-mediated activation of endothelial nitric oxide synthase. Cardiovasc Res, 93(1), 120-129.
Huang, H. J., Wang, Y. T., Lin, H. C., Lee, Y. H., & Lin, A. M. (2018). Soluble Epoxide Hydrolase Inhibition Attenuates MPTP-Induced Neurotoxicity in the Nigrostriatal Dopaminergic System: Involvement of alpha-Synuclein Aggregation and ER Stress. Mol Neurobiol, 55(1), 138-144.
Hung, C. C., Lin, C. H., Chang, H., Wang, C. Y., Lin, S. H., Hsu, P. C., Sun, Y. Y., Lin, T. N., Shie, F. S., Kao, L. S., Chou, C. M., & Lee, Y. H. (2016). Astrocytic GAP43 Induced by the TLR4/NF-kappaB/STAT3 Axis Attenuates Astrogliosis-Mediated Microglial Activation and Neurotoxicity. J Neurosci, 36(6), 2027-2043.
Hung, Y. W., Hung, S. W., Wu, Y. C., Wong, L. K., Lai, M. T., Shih, Y. H., Lee, T. S., & Lin, Y. Y. (2015). Soluble epoxide hydrolase activity regulates inflammatory responses and seizure generation in two mouse models of temporal lobe epilepsy. Brain, Behav, Immun, 43, 118-129.
Ibanez, I., Diez-Guerra, F. J., Gimenez, C., & Zafra, F. (2016). Activity dependent internalization of the glutamate transporter GLT-1 mediated by beta-arrestin 1 and ubiquitination. Neuropharmacology, 107, 376-386.
Iliff, J. J., & Alkayed, N. J. (2009). Soluble Epoxide Hydrolase Inhibition: Targeting Multiple Mechanisms of Ischemic Brain Injury with a Single Agent. Future Neurol, 4(2), 179-199.
Imig, J. D. (2012). Epoxides and soluble epoxide hydrolase in cardiovascular physiology. Physiol Rev, 92(1), 101-130.
Imig, J. D., & Hammock, B. D. (2009). Soluble epoxide hydrolase as a therapeutic target for cardiovascular diseases. Nat Rev Drug Discov, 8(10), 794-805.
Inceoglu, B., Zolkowska, D., Yoo, H. J., Wagner, K. M., Yang, J., Hackett, E., Hwang, S. H., Lee, K. S., Rogawski, M. A., Morisseau, C., & Hammock, B. D. (2013). Epoxy fatty acids and inhibition of the soluble epoxide hydrolase selectively modulate GABA mediated neurotransmission to delay onset of seizures. PLoS One, 8(12), e80922.
Jung, S., Aliberti, J., Graemmel, P., Sunshine, M. J., Kreutzberg, G. W., Sher, A., & Littman, D. R. (2000). Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol Cell Biol, 20(11), 4106-4114.
Kobayashi, E., Nakano, M., Kubota, K., Himuro, N., Mizoguchi, S., Chikenji, T., Otani, M., Mizue, Y., Nagaishi, K., & Fujimiya, M. (2018). Activated forms of astrocytes with higher GLT-1 expression are associated with cognitive normal subjects with Alzheimer pathology in human brain. Sci Rep, 8(1), 1712.
Koehler, R. C., Roman, R. J., & Harder, D. R. (2009). Astrocytes and the regulation of cerebral blood flow. Trends Neurosci, 32(3), 160-169.
Koerner, I. P., Jacks, R., DeBarber, A. E., Koop, D., Mao, P., Grant, D. F., & Alkayed, N. J. (2007). Polymorphisms in the human soluble epoxide hydrolase gene EPHX2 linked to neuronal survival after ischemic injury. J Neurosci, 27(17), 4642-4649.
Kundu, S., Roome, T., Bhattacharjee, A., Carnevale, K. A., Yakubenko, V. P., Zhang, R., Hwang, S. H., Hammock, B. D., & Cathcart, M. K. (2013). Metabolic products of soluble epoxide hydrolase are essential for monocyte chemotaxis to MCP-1 in vitro and in vivo. J Lipid Res, 54(2), 436-447.
Lavialle, M., Aumann, G., Anlauf, E., Prols, F., Arpin, M., & Derouiche, A. (2011). Structural plasticity of perisynaptic astrocyte processes involves ezrin and metabotropic glutamate receptors. Proc Natl Acad Sci U S A, 108(31), 12915-12919.
Li, L., Li, N., Pang, W., Zhang, X., Hammock, B. D., Ai, D., & Zhu, Y. (2014). Opposite effects of gene deficiency and pharmacological inhibition of soluble epoxide hydrolase on cardiac fibrosis. PLoS One, 9(4), e94092.
Liddelow, S. A., & Barres, B. A. (2017). Reactive Astrocytes: Production, Function, and Therapeutic Potential. Immunity, 46(6), 957-967.
Lin, C. H., Juan, S. H., Wang, C. Y., Sun, Y. Y., Chou, C. M., Chang, S. F., Hu, S. Y., Lee, W. S., & Lee, Y. H. (2008). Neuronal activity enhances aryl hydrocarbon receptor-mediated gene expression and dioxin neurotoxicity in cortical neurons. J Neurochem, 104(5), 1415-1429.
Liu, M., & Alkayed, N. J. (2005). Hypoxic preconditioning and tolerance via hypoxia inducible factor (HIF) 1alpha-linked induction of P450 2C11 epoxygenase in astrocytes. J Cereb Blood Flow Metab, 25(8), 939-948.
Liu, M., Zhu, Q., Wu, J., Yu, X., Hu, M., Xie, X., Yang, Z., Yang, J., Feng, Y. Q., & Yue, J. (2017). Glutamate affects the production of epoxyeicosanoids within the brain: The up-regulation of brain CYP2J through the MAPK-CREB signaling pathway. Toxicology, 381, 31-38.
Ma, D., Tao, B., Warashina, S., Kotani, S., Lu, L., Kaplamadzhiev, D. B., Mori, Y., Tonchev, A. B., & Yamashima, T. (2007). Expression of free fatty acid receptor GPR40 in the central nervous system of adult monkeys. Neurosci Res, 58(4), 394-401.
Ma, J., Zhang, L., Han, W., Shen, T., Ma, C., Liu, Y., Nie, X., Liu, M., Ran, Y., & Zhu, D. (2012). Activation of JNK/c-Jun is required for the proliferation, survival, and angiogenesis induced by EET in pulmonary artery endothelial cells. J Lipid Res, 53(6), 1093-1105.
MacVicar, B. A., & Newman, E. A. (2015). Astrocyte regulation of blood flow in the brain. Cold Spring Harb Perspect Biol, 7(5), a020388.
Mahmoud, S., Gharagozloo, M., Simard, C., & Gris, D. (2019). Astrocytes Maintain Glutamate Homeostasis in the CNS by Controlling the Balance between Glutamate Uptake and Release. Cells, 8(2), E184.
Malherbe, P., Kratochwil, N., Zenner, M. T., Piussi, J., Diener, C., Kratzeisen, C., Fischer, C., & Porter, R. H. (2003). Mutational analysis and molecular modeling of the binding pocket of the metabotropic glutamate 5 receptor negative modulator 2-methyl-6-(phenylethynyl)-pyridine. Mol Pharmacol, 64(4), 823-832.
Mark, L. P., Prost, R. W., Ulmer, J. L., Smith, M. M., Daniels, D. L., Strottmann, J. M., Brown, W. D., & Hacein-Bey, L. (2001). Pictorial review of glutamate excitotoxicity: fundamental concepts for neuroimaging. AJNR Am J Neuroradiol, 22(10), 1813-1824.
Marowsky, A., Burgener, J., Falck, J. R., Fritschy, J. M., & Arand, M. (2009). Distribution of soluble and microsomal epoxide hydrolase in the mouse brain and its contribution to cerebral epoxyeicosatrienoic acid metabolism. Neuroscience, 163(2), 646-661.
Morisseau, C., & Hammock, B. D. (2013). Impact of soluble epoxide hydrolase and epoxyeicosanoids on human health. Annu Rev Pharmacol Toxicol, 53, 37-58.
Morisseau, C., Inceoglu, B., Schmelzer, K., Tsai, H. J., Jinks, S. L., Hegedus, C. M., & Hammock, B. D. (2010). Naturally occurring monoepoxides of eicosapentaenoic acid and docosahexaenoic acid are bioactive antihyperalgesic lipids. J Lipid Res, 51(12), 3481-3490.
Mule, N. K., Orjuela Leon, A. C., Falck, J. R., Arand, M., & Marowsky, A. (2017). 11,12 -Epoxyeicosatrienoic acid (11,12 EET) reduces excitability and excitatory transmission in the hippocampus. Neuropharmacology, 123, 310-321.
Nakajima, K., Yamamoto, S., Kohsaka, S., & Kurihara, T. (2008). Neuronal stimulation leading to upregulation of glutamate transporter-1 (GLT-1) in rat microglia in vitro. Neurosci Lett, 436(3), 331-334.
Newman, J. W., Morisseau, C., Harris, T. R., & Hammock, B. D. (2003). The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme with novel lipid phosphate phosphatase activity. Proc Natl Acad Sci U S A, 100(4), 1558-1563.
Niswender, C. M., & Conn, P. J. (2010). Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol, 50, 295-322.
Olney, J. W. (1969). Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science, 164(3880), 719-721.
Panatier, A., & Robitaille, R. (2016). Astrocytic mGluR5 and the tripartite synapse. Neuroscience, 323, 29-34.
Park, S. K., Herrnreiter, A., Pfister, S. L., Gauthier, K. M., Falck, B. A., Falck, J. R., & Campbell, W. B. (2018). GPR40 is a low-affinity epoxyeicosatrienoic acid receptor in vascular cells. J Biol Chem, 293(27), 10675-10691.
Perez-Alvarez, A., Navarrete, M., Covelo, A., Martin, E. D., & Araque, A. (2014). Structural and functional plasticity of astrocyte processes and dendritic spine interactions. J Neurosci, 34(38), 12738-12744.
Qu, Y., Liu, Y., Zhu, Y., Chen, L., Sun, W., & Zhu, Y. (2017). Epoxyeicosatrienoic Acid Inhibits the Apoptosis of Cerebral Microvascular Smooth Muscle Cells by Oxygen Glucose Deprivation via Targeting the JNK/c-Jun and mTOR Signaling Pathways. Mol Cells, 40(11), 837-846.
Reiner, A., & Levitz, J. (2018). Glutamatergic Signaling in the Central Nervous System: Ionotropic and Metabotropic Receptors in Concert. Neuron, 98(6), 1080-1098.
Ren, Q., Ma, M., Ishima, T., Morisseau, C., Yang, J., Wagner, K. M., Zhang, J. C., Yang, C., Yao, W., Dong, C., Han, M., Hammock, B. D., & Hashimoto, K. (2016). Gene deficiency and pharmacological inhibition of soluble epoxide hydrolase confers resilience to repeated social defeat stress. Proc Natl Acad Sci U S A, 113(13), E1944-1952.
Reus, G. Z., Abelaira, H. M., Tuon, T., Titus, S. E., Ignacio, Z. M., Rodrigues, A. L., & Quevedo, J. (2016). Glutamatergic NMDA Receptor as Therapeutic Target for Depression. Adv Protein Chem Struct Biol, 103, 169-202.
Rojo, A. I., Innamorato, N. G., Martin-Moreno, A. M., De Ceballos, M. L., Yamamoto, M., & Cuadrado, A. (2010). Nrf2 regulates microglial dynamics and neuroinflammation in experimental Parkinson's disease. Glia, 58(5), 588-598.
Rose, C. R., Felix, L., Zeug, A., Dietrich, D., Reiner, A., & Henneberger, C. (2017). Astroglial Glutamate Signaling and Uptake in the Hippocampus. Front Mol Neurosci, 10, 451.
Rossi, D., Brambilla, L., Valori, C. F., Roncoroni, C., Crugnola, A., Yokota, T., Bredesen, D. E., & Volterra, A. (2008). Focal degeneration of astrocytes in amyotrophic lateral sclerosis. Cell Death Differ, 15(11), 1691-1700.
Sakers, K., Lake, A. M., Khazanchi, R., Ouwenga, R., Vasek, M. J., Dani, A., & Dougherty, J. D. (2017). Astrocytes locally translate transcripts in their peripheral processes. Proc Natl Acad Sci U S A, 114(19), E3830-E3838.
Sanna, M. D., Ghelardini, C., & Galeotti, N. (2015). Activation of JNK pathway in spinal astrocytes contributes to acute ultra-low-dose morphine thermal hyperalgesia. Pain, 156(7), 1265-1275.
Sattler, R., & Tymianski, M. (2001). Molecular mechanisms of glutamate receptor-mediated excitotoxic neuronal cell death. Mol Neurobiol, 24(1-3), 107-129.
Schmelzer, K. R., Kubala, L., Newman, J. W., Kim, I. H., Eiserich, J. P., & Hammock, B. D. (2005). Soluble epoxide hydrolase is a therapeutic target for acute inflammation. Proc Natl Acad Sci U S A, 102(28), 9772-9777.
Schousboe, A., Scafidi, S., Bak, L. K., Waagepetersen, H. S., & McKenna, M. C. (2014). Glutamate metabolism in the brain focusing on astrocytes. Adv Neurobiol, 11, 13-30.
Sellers, K. W., Sun, C., Diez-Freire, C., Waki, H., Morisseau, C., Falck, J. R., Hammock, B. D., Paton, J. F., & Raizada, M. K. (2005). Novel mechanism of brain soluble epoxide hydrolase-mediated blood pressure regulation in the spontaneously hypertensive rat. FASEB J, 19(6), 626-628.
Spector, A. A., & Norris, A. W. (2007). Action of epoxyeicosatrienoic acids on cellular function. Am J Physiol Cell Physiol, 292(3), C996-1012.
Spigolon, G., Veronesi, C., Bonny, C., & Vercelli, A. (2010). c-Jun N-terminal kinase signaling pathway in excitotoxic cell death following kainic acid-induced status epilepticus. Eur J Neurosci, 31(7), 1261-1272.
Stagi, M., Gorlovoy, P., Larionov, S., Takahashi, K., & Neumann, H. (2006). Unloading kinesin transported cargoes from the tubulin track via the inflammatory c-Jun N-terminal kinase pathway. FASEB J, 20(14), 2573-2575.
Sura, P., Sura, R., Enayetallah, A. E., & Grant, D. F. (2008). Distribution and expression of soluble epoxide hydrolase in human brain. J Histochem Cytochem, 56(6), 551-559.
Takahashi, K., Foster, J. B., & Lin, C. L. (2015). Glutamate transporter EAAT2: regulation, function, and potential as a therapeutic target for neurological and psychiatric disease. Cell Mol Life Sci, 72(18), 3489-3506.
Takuma, K., Baba, A., & Matsuda, T. (2004). Astrocyte apoptosis: implications for neuroprotection. Prog Neurobiol, 72(2), 111-127.
Terashvili, M., Sarkar, P., Nostrand, M. V., Falck, J. R., & Harder, D. R. (2012). The protective effect of astrocyte-derived 14,15-epoxyeicosatrienoic acid on hydrogen peroxide-induced cell injury in astrocyte-dopaminergic neuronal cell line co-culture. Neuroscience, 223, 68-76.
Tian, D. S., Peng, J., Murugan, M., Feng, L. J., Liu, J. L., Eyo, U. B., Zhou, L. J., Mogilevsky, R., Wang, W., & Wu, L. J. (2017). Chemokine CCL2-CCR2 Signaling Induces Neuronal Cell Death via STAT3 Activation and IL-1beta Production after Status Epilepticus. J Neurosci, 37(33), 7878-7892.
Torres-Platas, S. G., Comeau, S., Rachalski, A., Bo, G. D., Cruceanu, C., Turecki, G., Giros, B., & Mechawar, N. (2014). Morphometric characterization of microglial phenotypes in human cerebral cortex. J Neuroinflammation, 11, 12.
Trabelsi, Y., Amri, M., Becq, H., Molinari, F., & Aniksztejn, L. (2017). The conversion of glutamate by glutamine synthase in neocortical astrocytes from juvenile rat is important to limit glutamate spillover and peri/extrasynaptic activation of NMDA receptors. Glia, 65(2), 401-415.
Ulas, J., Satou, T., Ivins, K. J., Kesslak, J. P., Cotman, C. W., & Balazs, R. (2000). Expression of metabotropic glutamate receptor 5 is increased in astrocytes after kainate-induced epileptic seizures. Glia, 30(4), 352-361.
Umpierre, A. D., West, P. J., White, J. A., & Wilcox, K. S. (2019). Conditional Knockout of mGluR5 from Astrocytes during Epilepsy Development Impairs High-Frequency Glutamate Uptake. J Neurosci, 39(4), 727-742.
Varvel, N. H., Neher, J. J., Bosch, A., Wang, W., Ransohoff, R. M., Miller, R. J., & Dingledine, R. (2016). Infiltrating monocytes promote brain inflammation and exacerbate neuronal damage after status epilepticus. Proc Natl Acad Sci U S A, 113(38), E5665-5674.
Vermeiren, C., Najimi, M., Vanhoutte, N., Tilleux, S., de Hemptinne, I., Maloteaux, J. M., & Hermans, E. (2005). Acute up-regulation of glutamate uptake mediated by mGluR5a in reactive astrocytes. J Neurochem, 94(2), 405-416.
Vezzani, A., Balosso, S., & Ravizza, T. (2008). The role of cytokines in the pathophysiology of epilepsy. Brain Behav Immun, 22(6), 797-803.
Viviani, B., Boraso, M., Marchetti, N., & Marinovich, M. (2014). Perspectives on neuroinflammation and excitotoxicity: a neurotoxic conspiracy? Neurotoxicology, 43, 10-20.
Wang, J. Q., Fibuch, E. E., & Mao, L. (2007). Regulation of mitogen-activated protein kinases by glutamate receptors. J Neurochem, 100(1), 1-11.
Wu, C. H., Shyue, S. K., Hung, T. H., Wen, S., Lin, C. C., Chang, C. F., & Chen, S. F. (2017a). Genetic deletion or pharmacological inhibition of soluble epoxide hydrolase reduces brain damage and attenuates neuroinflammation after intracerebral hemorrhage. J Neuroinflammation, 14(1), 230.
Wu, H. F., Chen, Y. J., Wu, S. Z., Lee, C. W., Chen, I. T., Lee, Y. C., Huang, C. C., Hsing, C. H., Tang, C. W., & Lin, H. C. (2017b). Soluble Epoxide Hydrolase Inhibitor and 14,15-Epoxyeicosatrienoic Acid-Facilitated Long-Term Potentiation through cAMP and CaMKII in the Hippocampus. Neural Plast, 2017, 3467805.
Wu, H. F., Yen, H. J., Huang, C. C., Lee, Y. C., Wu, S. Z., Lee, T. S., & Lin, H. C. (2015). Soluble epoxide hydrolase inhibitor enhances synaptic neurotransmission and plasticity in mouse prefrontal cortex. J Biomed Sci, 22, 94.
Wu, P. C., & Kao, L. S. (2016). Calcium regulation in mouse mesencephalic neurons-Differential roles of Na(+)/Ca(2+) exchanger, mitochondria and endoplasmic reticulum. Cell Calcium, 59(6), 299-311.
Xie, C., Sun, J., Qiao, W., Lu, D., Wei, L., Na, M., Song, Y., Hou, X., & Lin, Z. (2011). Administration of simvastatin after kainic acid-induced status epilepticus restrains chronic temporal lobe epilepsy. PLoS One, 6(9), e24966.
Yang, D., Sun, Y. Y., Bhaumik, S. K., Li, Y., Baumann, J. M., Lin, X., Zhang, Y., Lin, S. H., Dunn, R. S., Liu, C. Y., Shie, F. S., Lee, Y. H., Wills-Karp, M., Chougnet, C. A., Kallapur, S. G., Lewkowich, I. P., Lindquist, D. M., Murali-Krishna, K., & Kuan, C. Y. (2014). Blocking lymphocyte trafficking with FTY720 prevents inflammation-sensitized hypoxic-ischemic brain injury in newborns. J Neurosci, 34(49), 16467-16481.
Yang, Y., Tian, X., Xu, D., Zheng, F., Lu, X., Zhang, Y., Ma, Y., Li, Y., Xu, X., Zhu, B., & Wang, X. (2018). GPR40 modulates epileptic seizure and NMDA receptor function. Sci Adv, 4(10), eaau2357.
Yuan, L., Liu, J., Dong, R., Zhu, J., Tao, C., Zheng, R., & Zhu, S. (2016). 14,15-epoxyeicosatrienoic acid promotes production of BDNF from astrocytes and exerts neuroprotective effects during ischemic injury. Neuropathol Appl Neurobiol, 42(7), 607-620.
Zhang, K., Wang, H., Xu, M., Frank, J. A., & Luo, J. (2018). Role of MCP-1 and CCR2 in ethanol-induced neuroinflammation and neurodegeneration in the developing brain. J Neuroinflammation, 15(1), 197.
Zhang, L., Ding, H., Yan, J., Hui, R., Wang, W., Kissling, G. E., Zeldin, D. C., & Wang, D. W. (2008a). Genetic variation in cytochrome P450 2J2 and soluble epoxide hydrolase and risk of ischemic stroke in a Chinese population. Pharmacogenet Genomics, 18(1), 45-51.
Zhang, W., Koerner, I. P., Noppens, R., Grafe, M., Tsai, H. J., Morisseau, C., Luria, A., Hammock, B. D., Falck, J. R., & Alkayed, N. J. (2007). Soluble epoxide hydrolase: a novel therapeutic target in stroke. J Cereb Blood Flow Metab, 27(12), 1931-1940.
Zhang, W., Otsuka, T., Sugo, N., Ardeshiri, A., Alhadid, Y. K., Iliff, J. J., DeBarber, A. E., Koop, D. R., & Alkayed, N. J. (2008b). Soluble epoxide hydrolase gene deletion is protective against experimental cerebral ischemia. Stroke, 39(7), 2073-2078.
Zheng, S., Eacker, S. M., Hong, S. J., Gronostajski, R. M., Dawson, T. M., & Dawson, V. L. (2010). NMDA-induced neuronal survival is mediated through nuclear factor I-A in mice. J Clin Invest, 120(7), 2446-2456.
Zhou, J., & Sutherland, M. L. (2004). Glutamate transporter cluster formation in astrocytic processes regulates glutamate uptake activity. J Neurosci, 24(28), 6301-6306.