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研究生:黃佩宇
研究生(外文):Pei-Yu Huang
論文名稱:移植人類臍帶瓦頓氏凝膠內之間質幹細胞治療毛果芸香鹼誘發大白鼠癲癇的潛能
論文名稱(外文):Xenograft of Human Umbilical Mesenchymal Stem Cells from Wharton’s Jelly as A Potential Therapy for the Rat Pilocarpine-Induced Epilepsy
指導教授:林永煬林永煬引用關係傅毓秀傅毓秀引用關係
指導教授(外文):Yung-Yang LinYu-Show Fu
學位類別:博士
校院名稱:國立陽明大學
系所名稱:生理學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2016
畢業學年度:104
語文別:英文
論文頁數:84
中文關鍵詞:人類臍帶間質幹細胞瓦頓氏凝膠顳葉癲癇持續癲癇發作狀態細胞移植幹細胞療法神經保護作用細胞激素興奮性毒性
外文關鍵詞:Human umbilical mesenchymal stem cellsWharton’s jellyTemporal lobe epilepsyStatus epilepticusCell transplantationStem cell therapyNeuroprotectionCytokinesExcitotoxicity
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本實驗探討移植人類臍帶間質幹細胞對於癲癇疾病的治療成效以及相關機轉。首先,我們移植人類臍帶間質幹細胞至大鼠雙側海馬迴中,並將大鼠先行投予毛果芸香鹼 (pilocarpine)。實驗大鼠分為三組: (1) 正常組 (Normal group):大鼠腹腔注射PBS、(2) 癲癇組 (status epilepticus group,SE group):給予毛果芸香鹼誘使大鼠產生持續癲癇發作狀態 (status epilepticus),並注射PBS到大鼠海馬迴區域、(3) 幹細胞移植組 (SE+HUMSCs group):移植人類臍帶間質幹細胞到癲癇大鼠中。利用同步影像與腦電圖 (electroencephalographic,EEG) 記錄癲癇組及幹細胞移植組大鼠的自發性反覆運動發作 (Spontaneous recurrent motor seizures,SRMS),觀察大鼠在持續癲癇發作狀態後2 - 4週內的自發性反覆運動發作時間及單次發作間期,並從中評估移植人類臍帶間質幹細胞的作用。研究結果顯示,幹細胞移植組的自發性反覆運動發作的發生有延遲的現象,且較少大鼠有自發性反覆運動發作。此外,在2 - 4週中幹細胞移植組的自發性反覆運動發作數目與單次發作間期相較於癲癇組有顯著的降低。所有大鼠均在誘發持續癲癇發作狀態後第29天犧牲。利用非侵入性的磁振造影 (magnetic resonance imaging,MRI) 與結晶紫染色 (Nissl staining) 判斷腦水腫、海馬迴構形改變與海馬迴體積。結果表示,癲癇組的腦水腫程度與背側海馬迴 (dorsal hippocampus) 體積相較於正常組與幹細胞治療組均有明顯的減少。組織化學研究結果顯示,癲癇組大鼠在CA1與CA3區域的錐體神經細胞 (pyramidal neurons) 數目相較於正常組與幹細胞治療組有嚴重的減少。細胞移植組與正常組的海馬迴區域神經細胞以及抑制性神經細胞 (GABAergic) 的細胞數目均無顯著性的差異。相較於癲癇組,幹細胞移植組顯示抑制星狀膠細胞 (astrocyte)、微膠細胞 (microglia) 的活化以及阻止常苔狀纖維異常增生 (aberrant mossy fiber sprouting)。移植的人類臍帶間質幹細胞可存活在海馬迴位置達29天。此外,我們也發現人類滋養因子 (trophic factor) 與細胞激素 (cytokines) 表現在移植人類臍帶間質幹細胞的大鼠海馬迴中,包括 amphiregulin (AREG)、fibroblast growth factor-6 (FGF-6)、glucocorticoid-induced tumor necrosis factor receptor (GITR)、macrophage inflammatory protein- 3β (MIP-3β) 與osteoprotegerin (OPG)。因此,藉由in vitro研究進一步探討上述細胞激素的神經保護作用。麩胺酸造成的神經興奮性毒性 (glutamate excitotoxicity) 與急性 (acute) 與慢性 (chronic) 的神經退化性疾病 (neurodegeneration diseases) 均有相關性。將皮質神經細胞 (cortical neurons) 培養在含麩胺酸的環境,發現細胞存活率有明顯的降低,且細胞凋亡與氧化壓力則明顯的增加。共同培養 (co-culture) 神經細胞與人類臍帶間質幹細胞可避免麩胺酸引發的神經細胞損傷。事實上,當神經細胞與人類臍帶間質幹細胞共同培養時,人類臍帶間質幹細胞會釋放大量的AREG、OPG與TGF-β1 (transforming growth factor-β1) 到培養液中。TGF-β1是一種與損傷相關的胜肽,可參與細胞的修復。將大鼠的皮質細胞培養在含AREG、FGF-6、MIP-3β與OPG的培養液中,可保護細胞免於受到麩胺酸引發的損傷。這些滋養因子與細胞激素的神經保護作用,證實了人類臍帶間質幹細胞在神經疾病中的旁分泌作用 (paracrine effect)。綜合以上結果,我們的結果顯示,移植人類臍帶間質幹細胞可抑制癲癇的發展以及保護神經細胞免於受到麩胺酸造成的神經興奮性毒性傷害。此外,幹細胞藉由產生具神經保護與抗發炎作用的細胞激素來達到上述的治療成效。本實驗結果也提供未來在癲癇疾病或麩胺酸相關神經疾病一個深具潛能的有效療法。
We evaluated the therapeutic benefits and underlying mechanisms of human umbilical mesenchymal stem cells (HUMSCs) on epilepsy. At first, we transplanted HUMSCs into bilateral hippocampus of pilocarpine-treated. The rats were divided into the following three groups: (1) a normal group of rats receiving only PBS, (2) a status epilepticus (SE) group of rats with pilocarpine-induced SE and PBS injected into the hippocampi, and (3) a SE+HUMSC group of SE rats with HUMSC transplantation. To examine the effects of HUMSC transplantation on the onset and the duration of spontaneous recurrent motor seizures (SRMS), pilocarpine-treated rats with PBS injection or HUMSCs implantation were monitored by simultaneous video and electroencephalographic recordings at two to four weeks after SE induction. The results showed that the onset of SRMS was delay and found that fewer SRMS occurred in rats in SE+HUMSCs group during all recording period. Furthermore, both number and duration of SRMS within two to four weeks after SE were significantly decreased in SE+HUMSCs rats compared with SE rats. All of the rats were sacrificed for the structural and cellular studies on Day 29 after SE. Brain edema, hippocampal morphology changes and hippocampal volume were evaluated by magnetic resonance imaging, a non-invasive imaging technology, and Nissl staining, respectively. The results showed that the brain edema and total volume of the dorsal hippocampus was smaller in SE rats compared with normal and SE+HUMSCs rats. Following, histochemical studies show the severe pyramidal neuron loss in CA1 and CA3 regions in the SE rats compared with the neuron number in normal and SE+HUMSCs rat. Interestingly, there were no significant differences in the number of hippocampal neurons and GABAergic neurons between normal and SE+HUMSCs rats. Compared with the SE rats, the SE+HUMSCs rats exhibited a suppression of astrocyte activity, microglia activation and aberrant mossy fiber sprouting. The implanted HUMSCs survived in the hippocampus at Day 29. In addition, we found the expression of human trophic factors and cytokines, including amphiregulin (AREG), fibroblast growth factor-6 (FGF-6), glucocorticoid-induced tumor necrosis factors receptor (GITR), macrophage inflammatory protein-3β (MIP-3β), and osteoprotegerin (OPG), in rat hippocampus with HUMSCs transplantation by human cytokine arrays. Accordingly, the further neuroprotective effects of these cytokines were examined through an in vitro study. Glutamate excitotoxicity was associated with many acute or chronic neurodegenerative diseases. Exposure of cortical neurons to glutamate showed a significant decrease in cell viability, and increase of cell apoptosis and oxidative stress. These glutamate-induced neuronal damages were prevented by co-culturing with HUMSCs. In fact, HUMSCs secreted abundant human AREG, OPG and transforming growth factor-β1 (TGF-β1) in the culture media when HUMSCs co-cultured with neurons. TGF-β1 is an injury-related peptide and is involved in tissue repair. Exposure of AREG, FGF-6, MIP-3β and OPG in cultured medium could protect rat cortical neurons from glutamate-induced cell death. The neuroprotective effects of these trophic factors or cytokines verified the paracrine effects of HUMSCs in neurologic diseases. Taken together, our results indicate that grafted HUMSC suppress the development of epilepsy and protect neurons from glutamate-induced excitotoxicity. Moreover, the above therapeutic effects are likely due to the ability of the cells to produce neuroprotective and anti-inflammatory cytokines. This finding provides a potential effective therapy for epilepsy or glutamate-associated neurologic diseases in the future.
Chinese Abstract i
English Abstract iii
Contents vi
List of Figures x
Chapter 1 Introduction 1
1.1 Literature review 1
1.1.1 Epilepsy 1
1.1.2. Classification of epilepsy 1
1.1.3 The characteristics of temporal lobe epilepsy 2
1.1.4 The progression of temporal lobe epilepsy 2
1.1.5 The pathology of temporal lobe epilepsy 3
1.1.5.1 Hippocampal sclerosis (HS) 3
1.1.5.2 Gliosis 4
1.1.5.3 Mossy fiber sprouting (MFS) 5
1.1.6 The mechanism of temporal lobe epilepsy 6
1.1.7 Experimental models of temporal lobe epilepsy 7
1.1.7.1 Pilocarpine model 7
1.1.7.2 Kainic acid model 8
1.1.7.3 Kindling model 8
1.1.7.4 In vitro models of epilepsy 9
1.1.8 Therapy of temporal lobe epilepsy 10
1.1.8.1 Surgical therapy 10
1.1.8.2 Antiepileptic drugs (AEDs) 11
1.1.8.3 Cell therapy 12
1.1.8.4 Neurotrophic factors therapy 13
1.2 The specific aims addressed in this dissertation 15
1.2.1 Part 1: Xenograft of human umbilical mesenchymal stem cells from Wharton’s jelly as a potential therapy for rat pilocarpine-induced epilepsy 15
1.2.2 Part 2: Human umbilical mesenchymal stem cells protect rat cortical neurons from glutamate-induced excitotoxicity by paracrine effect 15
Chapter 2 Xenograft of human umbilical mesenchymal stem cells from Wharton’s jelly as a potential therapy for rat pilocarpine-induced epilepsy 16
2.1 Introduction 16
2.2 Methods 18
2.2.1 Animals 18
2.2.2 Isolation and preparation of HUMSCs 18
2.2.3 Primary culture of rat cortical neurons 19
2.2.4 Culture systems of rat cortical neurons alone or neurons and HUMSCs co-cultures 19
2.2.5 The assessment of neuron viability 20
2.2.6 Quantification of cytokine levels in vitro 20
2.2.7 Pilocarpine-induced SE 21
2.2.8. Transplantation of HUMSCs 21
2.2.9. Electroencephalography (EEG) monitoring and analysis 22
2.2.10. Magnetic resonance imaging (MRI) 22
2.2.11. Histological and immunohistochemical examinations 23
2.2.12. Nissl staining 24
2.2.13. Timm’s staining 24
2.2.14. Tracing of HUMSCs using bisbenzimide treatment and anti-human nuclear Ag immunohistochemistry 25
2.2.15. Human cytokine array 25
2.2.16. Reverse transcription PCR for detecting human NeuN and GFAP in the hippocampus 26
2.2.17. Quantification and statistical analyses 27
2.3 Results 27
2.3.1 HUMSC transplantation attenuated the incidence and duration of spontaneous recurrent seizures in the chronic phase 27
2.3.2 HUMSCs transplantation reduced brain edema in chronic epilepsy 28
2.3.3 HUMSC transplantation reduced hippocampal cytoarchitecture changes in chronic epilepsy 29
2.3.4 HUMSCs transplantation preserved the integrity of the hippocampal pyramidal neurons and inhibitory circuitry in chronic epilepsy 29
2.3.5 HUMSCs transplantation inhibited astrocyte and microglial cells activation in the chronic epilepsy 30
2.3.6 HUMSCs transplantation attenuated mossy fiber sprouting in chronic epilepsy 31
2.3.7 Survival and distribution of transplanted HUMSCs in the hippocampus 31
2.3.8 Transplanted HUMSCs remain undifferentiated in the host hippocampus. 31
2.3.9 Transplanted HUMSCs expressed several cytokines in the rat hippocampus 32
2.3.10 HUMSCs prevented glutamate-induced cytotoxicity in cultured cortical neurons 32
2.3.11 Human cytokines were detected in the medium of neurons and HUMSCs co-culture 33
2.4 Discussions 33
2.4.1 Effects of cell therapy of temporal lobe epilepsy 33
2.4.2 Morphological and pathological changes of rat hippocampus after pilocarpine induced-SE and the protective effects of cell treatment 34
2.4.3 The relative mechanisms of stem cell therapy 36
2.5 Figures 41
Chapter 3 Human umbilical mesenchymal stem cells protect rat cortical neurons from glutamate-induced excitotoxicity by paracrine effect 53
3.1 Introduction 53
3.2 Methods 54
3.2.1 Animals 54
3.2.2 Isolation and preparation of HUMSCs 55
3.2.3 Isolation and preparation of rat primary cortical neurons 55
3.2.4 Co-culture systems of rat cortical neurons and HUMSCs 56
3.2.5 Treatment of neurons with cytokines 56
3.2.6 The TUNEL assay and DAPI staining 57
3.2.7 Assessment of neuron cytotoxicity by MTT assay 57
3.2.8 Measurement of intracellular ROS 57
3.2.9 Quantification of cytokine levels in cultured medium by ELISA assay 58
3.2.10. Statistical analyses 58
3.3 Results 58
3.3.1 HUMSCs protect cortical neurons against glutamate-induced cell death and apoptosis 58
3.3.2 HUMSCs protect cultures neurons prevent glutamate-induced oxidative stress 59
3.3.3 HUMSCs-secreted cytokines protects neurons against glutamate excitotoxicity 60
3.3.4 TGF-β1 involved in the neuroprotection effect of HUMSCs 60
3.4 Discussions 61
3.4.1 The mechanisms of glutamate excitotoxicity 61
3.4.2 The benefits of stem cell therapy 61
3.4.3 The paracrine effects of stem cell therapy 62
3.5 Figures 64
Chapter 4 General Conclusion 68
References 69
Appendix 83

List of Figures
Figure 2-1. Antiepileptic effects of HUMSC transplantation on pilocarpine-induced SE 41
Figure 2-2. Brain edema examined using MRI and Nissl staining 43
Figure 2-3. HUMSCs transplantation alleviates pyramidal neurons and interneurons loss in the hippocampus after pilocarpine-induced SE 45
Figure 2-4. HUMSC transplantation attenuates the activation of neuroglial cells in the hippocampus after pilocarpine-induced SE 47
Figure 2-5. HUMSC transplantation decreases mossy fiber sprouting in the hippocampus after pilocarpine-induced SE 48
Figure 2-6. Photomicrographs showing the survival and migration of grafted HUMSCs in the rat hippocampus 50
Figure 2-7. HUMSCs released cytokines in the rat hippocampus and in the neuron and HUMSC co-cultures 52
Figure 3-1. HUMSCs protected rat cortical neurons from glutamate-induced excitotoxicity and oxidative stress 64
Figure 3-2. HUMSCs reduced glutamate-induced apoptosis in cortical neurons. Cell apoptosis was determined by TUNEL staining 65
Figure 3-3. Cytokines protected neurons from glutamate excitotoxicity 66
Figure 3-4. Expression of human TGF-β1 and rat TGF-β1 protein in cultured medium 67
Appendix 1. The progression of temporal lobe epilepsy 83
Appendix 2. The possible therapeutic interventions in temporal lobe epilepsy. 84


Abdanipour, A., Tiraihi, T., Mirnajafi-Zadeh, J., 2011. Improvement of the pilocarpine epilepsy model in rat using bone marrow stromal cell therapy. Neurological research 33, 625-632.
Abematsu, M., Tsujimura, K., Yamano, M., Saito, M., Kohno, K., Kohyama, J., Namihira, M., Komiya, S., Nakashima, K., 2010. Neurons derived from transplanted neural stem cells restore disrupted neuronal circuitry in a mouse model of spinal cord injury. The Journal of clinical investigation 120, 3255-3266.
Acharya, M.M., Hattiangady, B., Shetty, A.K., 2008. Progress in neuroprotective strategies for preventing epilepsy. Progress in neurobiology 84, 363-404.
Acsady, L., Kamondi, A., Sik, A., Freund, T., Buzsaki, G., 1998. GABAergic cells are the major postsynaptic targets of mossy fibers in the rat hippocampus. The Journal of neuroscience : the official journal of the Society for Neuroscience 18, 3386-3403.
Beach, T.G., Woodhurst, W.B., MacDonald, D.B., Jones, M.W., 1995. Reactive microglia in hippocampal sclerosis associated with human temporal lobe epilepsy. Neuroscience letters 191, 27-30.
Ben-Ari, Y., Lagowska, J., 1978. [Epileptogenic action of intra-amygdaloid injection of kainic acid]. Comptes rendus hebdomadaires des seances de l'Academie des sciences. Serie D: Sciences naturelles 287, 813-816.
Biagini, G., Baldelli, E., Longo, D., Pradelli, L., Zini, I., Rogawski, M.A., Avoli, M., 2006. Endogenous neurosteroids modulate epileptogenesis in a model of temporal lobe epilepsy. Exp Neurol 201, 519-524.
Binder, D.K., Steinhauser, C., 2006. Functional changes in astroglial cells in epilepsy. Glia 54, 358-368.
Bjorklund, A., 1993. Neurobiology. Better cells for brain repair. Nature 362, 414-415.
Blumcke, I., Thom, M., Aronica, E., Armstrong, D.D., Bartolomei, F., Bernasconi, A., Bernasconi, N., Bien, C.G., Cendes, F., Coras, R., Cross, J.H., Jacques, T.S., Kahane, P., Mathern, G.W., Miyata, H., Moshe, S.L., Oz, B., Ozkara, C., Perucca, E., Sisodiya, S., Wiebe, S., Spreafico, R., 2013. International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: a Task Force report from the ILAE Commission on Diagnostic Methods. Epilepsia 54, 1315-1329.
Boche, D., Cunningham, C., Gauldie, J., Perry, V.H., 2003. Transforming growth factor-beta 1-mediated neuroprotection against excitotoxic injury in vivo. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 23, 1174-1182.
Boison, D., 2009. Engineered adenosine-releasing cells for epilepsy therapy: human mesenchymal stem cells and human embryonic stem cells. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 6, 278-283.
Borges, K., Gearing, M., McDermott, D.L., Smith, A.B., Almonte, A.G., Wainer, B.H., Dingledine, R., 2003. Neuronal and glial pathological changes during epileptogenesis in the mouse pilocarpine model. Experimental neurology 182, 21-34.
Brodie, M.J., 1999. Monostars: an aid to choosing an antiepileptic drug as monotherapy. Epilepsia 40 Suppl 6, S17-22; discussion S73-14.
Brophy, G.M., Bell, R., Claassen, J., Alldredge, B., Bleck, T.P., Glauser, T., Laroche, S.M., Riviello, J.J., Jr., Shutter, L., Sperling, M.R., Treiman, D.M., Vespa, P.M., Neurocritical Care Society Status Epilepticus Guideline Writing, C., 2012. Guidelines for the evaluation and management of status epilepticus. Neurocritical care 17, 3-23.
Buckley, N.J., Bonner, T.I., Brann, M.R., 1988. Localization of a family of muscarinic receptor mRNAs in rat brain. The Journal of neuroscience : the official journal of the Society for Neuroscience 8, 4646-4652.
Buckmaster, P.S., Dudek, F.E., 1999. In vivo intracellular analysis of granule cell axon reorganization in epileptic rats. Journal of neurophysiology 81, 712-721.
Burda, J.E., Sofroniew, M.V., 2014. Reactive gliosis and the multicellular response to CNS damage and disease. Neuron 81, 229-248.
Burdon, T.J., Paul, A., Noiseux, N., Prakash, S., Shum-Tim, D., 2011. Bone marrow stem cell derived paracrine factors for regenerative medicine: current perspectives and therapeutic potential. Bone marrow research 2011, 207326.
Byrnes, H.D., Kaminski, H., Mirza, A., Deno, G., Lundell, D., Fine, J.S., 1999. Macrophage inflammatory protein-3 beta enhances IL-10 production by activated human peripheral blood monocytes and T cells. Journal of immunology 163, 4715-4720.
Cao, Q., Benton, R.L., Whittemore, S.R., 2002. Stem cell repair of central nervous system injury. Journal of neuroscience research 68, 501-510.
Carpentino, J.E., Hartman, N.W., Grabel, L.B., Naegele, J.R., 2008. Region-specific differentiation of embryonic stem cell-derived neural progenitor transplants into the adult mouse hippocampus following seizures. J Neurosci Res 86, 512-524.
Castillo, C.G., Mendoza, S., Freed, W.J., Giordano, M., 2006. Intranigral transplants of immortalized GABAergic cells decrease the expression of kainic acid-induced seizures in the rat. Behavioural brain research 171, 109-115.
Cavalheiro, E.A., Leite, J.P., Bortolotto, Z.A., Turski, W.A., Ikonomidou, C., Turski, L., 1991. Long-term effects of pilocarpine in rats: structural damage of the brain triggers kindling and spontaneous recurrent seizures. Epilepsia 32, 778-782.
Chang, B.S., Lowenstein, D.H., 2003. Epilepsy. The New England journal of medicine 349, 1257-1266.
Chao, K.C., Chao, K.F., Fu, Y.S., Liu, S.H., 2008. Islet-like clusters derived from mesenchymal stem cells in Wharton's Jelly of the human umbilical cord for transplantation to control type 1 diabetes. PloS one 3, e1451.
Chen, G., Gulbranson, D.R., Yu, P., Hou, Z., Thomson, J.A., 2012. Thermal stability of fibroblast growth factor protein is a determinant factor in regulating self-renewal, differentiation, and reprogramming in human pluripotent stem cells. Stem cells 30, 623-630.
Choi, D.W., 1985. Glutamate neurotoxicity in cortical cell culture is calcium dependent. Neuroscience letters 58, 293-297.
Choi, D.W., Maulucci-Gedde, M., Kriegstein, A.R., 1987. Glutamate neurotoxicity in cortical cell culture. The Journal of neuroscience : the official journal of the Society for Neuroscience 7, 357-368.
Chu, K., Kim, M., Jung, K.H., Jeon, D., Lee, S.T., Kim, J., Jeong, S.W., Kim, S.U., Lee, S.K., Shin, H.S., Roh, J.K., 2004. Human neural stem cell transplantation reduces spontaneous recurrent seizures following pilocarpine-induced status epilepticus in adult rats. Brain research 1023, 213-221.
Costa-Ferro, Z.S., Souza, B.S., Leal, M.M., Kaneto, C.M., Azevedo, C.M., da Silva, I.C., Soares, M.B., Ribeiro-dos-Santos, R., Dacosta, J.C., 2012. Transplantation of bone marrow mononuclear cells decreases seizure incidence, mitigates neuronal loss and modulates pro-inflammatory cytokine production in epileptic rats. Neurobiology of disease 46, 302-313.
Costa-Ferro, Z.S., Vitola, A.S., Pedroso, M.F., Cunha, F.B., Xavier, L.L., Machado, D.C., Soares, M.B., Ribeiro-dos-Santos, R., DaCosta, J.C., 2010. Prevention of seizures and reorganization of hippocampal functions by transplantation of bone marrow cells in the acute phase of experimental epilepsy. Seizure 19, 84-92.
Coyle, J.T., Puttfarcken, P., 1993. Oxidative stress, glutamate, and neurodegenerative disorders. Science 262, 689-695.
Cunningham, M., Cho, J.H., Leung, A., Savvidis, G., Ahn, S., Moon, M., Lee, P.K., Han, J.J., Azimi, N., Kim, K.S., Bolshakov, V.Y., Chung, S., 2014. hPSC-derived maturing GABAergic interneurons ameliorate seizures and abnormal behavior in epileptic mice. Cell stem cell 15, 559-573.
Curia, G., Longo, D., Biagini, G., Jones, R.S., Avoli, M., 2008. The pilocarpine model of temporal lobe epilepsy. Journal of neuroscience methods 172, 143-157.
De Simoni, M.G., Perego, C., Ravizza, T., Moneta, D., Conti, M., Marchesi, F., De Luigi, A., Garattini, S., Vezzani, A., 2000. Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus. The European journal of neuroscience 12, 2623-2633.
do Nascimento, A.L., Dos Santos, N.F., Campos Pelagio, F., Aparecida Teixeira, S., de Moraes Ferrari, E.A., Langone, F., 2012. Neuronal degeneration and gliosis time-course in the mouse hippocampal formation after pilocarpine-induced status epilepticus. Brain research 1470, 98-110.
Einstein, O., Fainstein, N., Vaknin, I., Mizrachi-Kol, R., Reihartz, E., Grigoriadis, N., Lavon, I., Baniyash, M., Lassmann, H., Ben-Hur, T., 2007. Neural precursors attenuate autoimmune encephalomyelitis by peripheral immunosuppression. Annals of neurology 61, 209-218.
Engel, J., Jr., 1996. Surgery for seizures. The New England journal of medicine 334, 647-652.
Engel, J., Jr., 1998. Classifications of the International League Against Epilepsy: time for reappraisal. Epilepsia 39, 1014-1017.
Engel, J., Jr., Wiebe, S., French, J., Sperling, M., Williamson, P., Spencer, D., Gumnit, R., Zahn, C., Westbrook, E., Enos, B., Quality Standards Subcommittee of the American Academy of, N., American Epilepsy, S., American Association of Neurological, S., 2003. Practice parameter: temporal lobe and localized neocortical resections for epilepsy: report of the Quality Standards Subcommittee of the American Academy of Neurology, in association with the American Epilepsy Society and the American Association of Neurological Surgeons. Neurology 60, 538-547.
Esclapez, M., Hirsch, J.C., Khazipov, R., Ben-Ari, Y., Bernard, C., 1997. Operative GABAergic inhibition in hippocampal CA1 pyramidal neurons in experimental epilepsy. Proceedings of the National Academy of Sciences of the United States of America 94, 12151-12156.
Falk, A., Frisen, J., 2002. Amphiregulin is a mitogen for adult neural stem cells. Journal of neuroscience research 69, 757-762.
Fawcett, J., 2009. Molecular control of brain plasticity and repair. Progress in brain research 175, 501-509.
Fisher, R.S., van Emde Boas, W., Blume, W., Elger, C., Genton, P., Lee, P., Engel, J., Jr., 2005. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 46, 470-472.
Fonnum, F., 1984. Glutamate: a neurotransmitter in mammalian brain. Journal of neurochemistry 42, 1-11.
Franck, J.E., Kunkel, D.D., Baskin, D.G., Schwartzkroin, P.A., 1988. Inhibition in kainate-lesioned hyperexcitable hippocampi: physiologic, autoradiographic, and immunocytochemical observations. The Journal of neuroscience : the official journal of the Society for Neuroscience 8, 1991-2002.
French, J.A., Kanner, A.M., Bautista, J., Abou-Khalil, B., Browne, T., Harden, C.L., Theodore, W.H., Bazil, C., Stern, J., Schachter, S.C., Bergen, D., Hirtz, D., Montouris, G.D., Nespeca, M., Gidal, B., Marks, W.J., Jr., Turk, W.R., Fischer, J.H., Bourgeois, B., Wilner, A., Faught, R.E., Jr., Sachdeo, R.C., Beydoun, A., Glauser, T.A., Therapeutics, Technology Assessment Subcommittee of the American Academy of, N., Quality Standards Subcommittee of the American Academy of, N., American Epilepsy, S., 2004. Efficacy and tolerability of the new antiepileptic drugs II: treatment of refractory epilepsy: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology 62, 1261-1273.
French, J.A., Williamson, P.D., Thadani, V.M., Darcey, T.M., Mattson, R.H., Spencer, S.S., Spencer, D.D., 1993. Characteristics of medial temporal lobe epilepsy: I. Results of history and physical examination. Annals of neurology 34, 774-780.
Fu, Y.S., Cheng, Y.C., Lin, M.Y., Cheng, H., Chu, P.M., Chou, S.C., Shih, Y.H., Ko, M.H., Sung, M.S., 2006. Conversion of human umbilical cord mesenchymal stem cells in Wharton's jelly to dopaminergic neurons in vitro: potential therapeutic application for Parkinsonism. Stem cells 24, 115-124.
Fu, Y.S., Shih, Y.T., Cheng, Y.C., Min, M.Y., 2004. Transformation of human umbilical mesenchymal cells into neurons in vitro. Journal of biomedical science 11, 652-660.
Gage, F.H., Coates, P.W., Palmer, T.D., Kuhn, H.G., Fisher, L.J., Suhonen, J.O., Peterson, D.A., Suhr, S.T., Ray, J., 1995. Survival and differentiation of adult neuronal progenitor cells transplanted to the adult brain. Proc Natl Acad Sci U S A 92, 11879-11883.
Gibbs, J.W., 3rd, Sombati, S., DeLorenzo, R.J., Coulter, D.A., 1997. Physiological and pharmacological alterations in postsynaptic GABA(A) receptor function in a hippocampal culture model of chronic spontaneous seizures. Journal of neurophysiology 77, 2139-2152.
Goddard, G.V., McIntyre, D.C., Leech, C.K., 1969. A permanent change in brain function resulting from daily electrical stimulation. Experimental neurology 25, 295-330.
Gong, C., Wang, T.W., Huang, H.S., Parent, J.M., 2007. Reelin regulates neuronal progenitor migration in intact and epileptic hippocampus. The Journal of neuroscience : the official journal of the Society for Neuroscience 27, 1803-1811.
Grall, F., Gu, X., Tan, L., Cho, J.Y., Inan, M.S., Pettit, A.R., Thamrongsak, U., Choy, B.K., Manning, C., Akbarali, Y., Zerbini, L., Rudders, S., Goldring, S.R., Gravallese, E.M., Oettgen, P., Goldring, M.B., Libermann, T.A., 2003. Responses to the proinflammatory cytokines interleukin-1 and tumor necrosis factor alpha in cells derived from rheumatoid synovium and other joint tissues involve nuclear factor kappaB-mediated induction of the Ets transcription factor ESE-1. Arthritis and rheumatism 48, 1249-1260.
Grande, J.P., 1997. Role of transforming growth factor-beta in tissue injury and repair. Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine 214, 27-40.
Gurnett, C.A., Landt, M., Wong, M., 2003. Analysis of cerebrospinal fluid glial fibrillary acidic protein after seizures in children. Epilepsia 44, 1455-1458.
Hamilton, S.E., Loose, M.D., Qi, M., Levey, A.I., Hille, B., McKnight, G.S., Idzerda, R.L., Nathanson, N.M., 1997. Disruption of the m1 receptor gene ablates muscarinic receptor-dependent M current regulation and seizure activity in mice. Proceedings of the National Academy of Sciences of the United States of America 94, 13311-13316.
Hammer, J., Alvestad, S., Osen, K.K., Skare, O., Sonnewald, U., Ottersen, O.P., 2008. Expression of glutamine synthetase and glutamate dehydrogenase in the latent phase and chronic phase in the kainate model of temporal lobe epilepsy. Glia 56, 856-868.
Hao, P., Liang, Z., Piao, H., Ji, X., Wang, Y., Liu, Y., Liu, R., Liu, J., 2014. Conditioned medium of human adipose-derived mesenchymal stem cells mediates protection in neurons following glutamate excitotoxicity by regulating energy metabolism and GAP-43 expression. Metabolic brain disease 29, 193-205.
Hattiangady, B., Rao, M.S., Shetty, A.K., 2004. Chronic temporal lobe epilepsy is associated with severely declined dentate neurogenesis in the adult hippocampus. Neurobiology of disease 17, 473-490.
Hattiangady, B., Shetty, A.K., 2008. Implications of decreased hippocampal neurogenesis in chronic temporal lobe epilepsy. Epilepsia 49 Suppl 5, 26-41.
Hattiangady, B., Shuai, B., Cai, J., Coksaygan, T., Rao, M.S., Shetty, A.K., 2007. Increased dentate neurogenesis after grafting of glial restricted progenitors or neural stem cells in the aging hippocampus. Stem cells 25, 2104-2117.
Hellier, J.L., Dudek, F.E., 2005. Chemoconvulsant model of chronic spontaneous seizures. Current protocols in neuroscience / editorial board, Jacqueline N. Crawley ... [et al.] Chapter 9, Unit 9 19.
Hoss, W., Woodruff, J.M., Ellerbrock, B.R., Periyasamy, S., Ghodsi-Hovsepian, S., Stibbe, J., Bohnett, M., Messer, W.S., Jr., 1990. Biochemical and behavioral responses of pilocarpine at muscarinic receptor subtypes in the CNS. Comparison with receptor binding and low-energy conformations. Brain research 533, 232-238.
Hsu, M., Buzsaki, G., 1993. Vulnerability of mossy fiber targets in the rat hippocampus to forebrain ischemia. The Journal of neuroscience : the official journal of the Society for Neuroscience 13, 3964-3979.
Huang, P.Y., Shih, Y.H., Tseng, Y.J., Ko, T.L., Fu, Y.S., Lin, Y.Y., 2016. Xenograft of human umbilical mesenchymal stem cells from Wharton's jelly as a potential therapy for rat pilocarpine-induced epilepsy. Brain, behavior, and immunity 54, 45-58.
Huicong, K., Zheng, X., Furong, W., Zhouping, T., Feng, X., Qi, H., Xiaoyan, L., Xiaojiang, H., Na, Z., Ke, X., Zheng, Z., Suiqiang, Z., 2013. The imbalanced expression of adenosine receptors in an epilepsy model corrected using targeted mesenchymal stem cell transplantation. Molecular neurobiology 48, 921-930.
Hunt, R.F., Girskis, K.M., Rubenstein, J.L., Alvarez-Buylla, A., Baraban, S.C., 2013. GABA progenitors grafted into the adult epileptic brain control seizures and abnormal behavior. Nature neuroscience 16, 692-697.
ILAE, C.R., 1989. Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia 30, 389-399.
ILAE, C.R., 1997. ILAE Commission Report. The epidemiology of the epilepsies: future directions. International League Against Epilepsy. Epilepsia 38, 614-618.
Itoh, K., Inamine, M., Oshima, W., Kotani, M., Chiba, Y., Ueno, M., Ishihara, Y., 2015. Prevention of status epilepticus-induced brain edema and neuronal cell loss by repeated treatment with high-dose levetiracetam. Brain research 1608, 225-234.
Jankowsky, J.L., Patterson, P.H., 2001. The role of cytokines and growth factors in seizures and their sequelae. Progress in neurobiology 63, 125-149.
Johnston, G.A., Curtis, D.R., Davies, J., McCulloch, R.M., 1974. Spinal interneurone excitation by conformationally restricted analogues of L-glutamic acid. Nature 248, 804-805.
Jones, M.K., Sasaki, E., Halter, F., Pai, R., Nakamura, T., Arakawa, T., Kuroki, T., Tarnawski, A.S., 1999. HGF triggers activation of the COX-2 gene in rat gastric epithelial cells: action mediated through the ERK2 signaling pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 13, 2186-2194.
Jung, K.H., Chu, K., Lee, S.T., Kim, J.H., Kang, K.M., Song, E.C., Kim, S.J., Park, H.K., Kim, M., Lee, S.K., Roh, J.K., 2009. Region-specific plasticity in the epileptic rat brain: a hippocampal and extrahippocampal analysis. Epilepsia 50, 537-549.
Kann, O., Kovacs, R., Njunting, M., Behrens, C.J., Otahal, J., Lehmann, T.N., Gabriel, S., Heinemann, U., 2005. Metabolic dysfunction during neuronal activation in the ex vivo hippocampus from chronic epileptic rats and humans. Brain : a journal of neurology 128, 2396-2407.
Kao, S.Y., Kempfle, J.S., Jensen, J.B., Perez-Fernandez, D., Lysaght, A.C., Edge, A.S., Stankovic, K.M., 2013. Loss of osteoprotegerin expression in the inner ear causes degeneration of the cochlear nerve and sensorineural hearing loss. Neurobiology of disease 56, 25-33.
Kato, K., Puttfarcken, P.S., Lyons, W.E., Coyle, J.T., 1991. Developmental time course and ionic dependence of kainate-mediated toxicity in rat cerebellar granule cell cultures. The Journal of pharmacology and experimental therapeutics 256, 402-411.
Kim, W.J., Park, S.C., Lee, S.J., Lee, J.H., Kim, J.Y., Lee, B.I., Kim, D.I., 1999. The prognosis for control of seizures with medications in patients with MRI evidence for mesial temporal sclerosis. Epilepsia 40, 290-293.
Kowalewski, R., Malkowski, A., Sobolewski, K., Gacko, M., 2010. Evaluation of transforming growth factor-beta signaling pathway in the wall of normal and varicose veins. Pathobiology : journal of immunopathology, molecular and cellular biology 77, 1-6.
Kwan, P., Brodie, M.J., 2000. Early identification of refractory epilepsy. The New England journal of medicine 342, 314-319.
Leal, M.M., Costa-Ferro, Z.S., Souza, B.S., Azevedo, C.M., Carvalho, T.M., Kaneto, C.M., Carvalho, R.H., Dos Santos, R.R., Soares, M.B., 2014. Early transplantation of bone marrow mononuclear cells promotes neuroprotection and modulation of inflammation after status epilepticus in mice by paracrine mechanisms. Neurochemical research 39, 259-268.
Lee, H., Yun, S., Kim, I.S., Lee, I.S., Shin, J.E., Park, S.C., Kim, W.J., Park, K.I., 2014. Human fetal brain-derived neural stem/progenitor cells grafted into the adult epileptic brain restrain seizures in rat models of temporal lobe epilepsy. PloS one 9, e104092.
Levey, A.I., Edmunds, S.M., Koliatsos, V., Wiley, R.G., Heilman, C.J., 1995. Expression of m1-m4 muscarinic acetylcholine receptor proteins in rat hippocampus and regulation by cholinergic innervation. The Journal of neuroscience : the official journal of the Society for Neuroscience 15, 4077-4092.
Li, T., Ren, G., Kaplan, D.L., Boison, D., 2009. Human mesenchymal stem cell grafts engineered to release adenosine reduce chronic seizures in a mouse model of CA3-selective epileptogenesis. Epilepsy research 84, 238-241.
Lin, Y.C., Ko, T.L., Shih, Y.H., Lin, M.Y., Fu, T.W., Hsiao, H.S., Hsu, J.Y., Fu, Y.S., 2011. Human umbilical mesenchymal stem cells promote recovery after ischemic stroke. Stroke; a journal of cerebral circulation 42, 2045-2053.
Long, Q., Qiu, B., Wang, K., Yang, J., Jia, C., Xin, W., Wang, P., Han, R., Fei, Z., Liu, W., 2013. Genetically engineered bone marrow mesenchymal stem cells improve functional outcome in a rat model of epilepsy. Brain research 1532, 1-13.
Loscher, W., Brandt, C., 2010. Prevention or modification of epileptogenesis after brain insults: experimental approaches and translational research. Pharmacological reviews 62, 668-700.
Lu, P., Jones, L.L., Snyder, E.Y., Tuszynski, M.H., 2003. Neural stem cells constitutively secrete neurotrophic factors and promote extensive host axonal growth after spinal cord injury. Experimental neurology 181, 115-129.
Macdonald, R.L., Kelly, K.M., 1995. Antiepileptic drug mechanisms of action. Epilepsia 36 Suppl 2, S2-12.
Majores, M., Schoch, S., Lie, A., Becker, A.J., 2007. Molecular neuropathology of temporal lobe epilepsy: complementary approaches in animal models and human disease tissue. Epilepsia 48 Suppl 2, 4-12.
Malmgren, K., Thom, M., 2012. Hippocampal sclerosis--origins and imaging. Epilepsia 53 Suppl 4, 19-33.
Mathern, G.W., Babb, T.L., Pretorius, J.K., Leite, J.P., 1995. Reactive synaptogenesis and neuron densities for neuropeptide Y, somatostatin, and glutamate decarboxylase immunoreactivity in the epileptogenic human fascia dentata. The Journal of neuroscience : the official journal of the Society for Neuroscience 15, 3990-4004.
Matsumoto, Y., Ohmori, K., Fujiwara, M., 1992. Microglial and astroglial reactions to inflammatory lesions of experimental autoimmune encephalomyelitis in the rat central nervous system. Journal of neuroimmunology 37, 23-33.
Mattson, M.P., 2008. Glutamate and neurotrophic factors in neuronal plasticity and disease. Annals of the New York Academy of Sciences 1144, 97-112.
McIntyre, D.C., Poulter, M.O., Gilby, K., 2002. Kindling: some old and some new. Epilepsy research 50, 79-92.
McKelvey, L., Gutierrez, H., Nocentini, G., Crampton, S.J., Davies, A.M., Riccardi, C.R., O'Keeffe G, W., 2012. The intracellular portion of GITR enhances NGF-promoted neurite growth through an inverse modulation of Erk and NF-kappaB signalling. Biology open 1, 1016-1023.
McNamara, J.O., 1994. Cellular and molecular basis of epilepsy. The Journal of neuroscience : the official journal of the Society for Neuroscience 14, 3413-3425.
Messer, W.S., Jr., Bohnett, M., Stibbe, J., 1990. Evidence for a preferential involvement of M1 muscarinic receptors in representational memory. Neuroscience letters 116, 184-189.
Michalakis, M., Holsinger, D., Ikeda-Douglas, C., Cammisuli, S., Ferbinteanu, J., DeSouza, C., DeSouza, S., Fecteau, J., Racine, R.J., Milgram, N.W., 1998. Development of spontaneous seizures over extended electrical kindling. I. Electrographic, behavioral, and transfer kindling correlates. Brain research 793, 197-211.
Mitchell, K.E., Weiss, M.L., Mitchell, B.M., Martin, P., Davis, D., Morales, L., Helwig, B., Beerenstrauch, M., Abou-Easa, K., Hildreth, T., Troyer, D., Medicetty, S., 2003. Matrix cells from Wharton's jelly form neurons and glia. Stem cells 21, 50-60.
Mitsui, K., Tokuzawa, Y., Itoh, H., Segawa, K., Murakami, M., Takahashi, K., Maruyama, M., Maeda, M., Yamanaka, S., 2003. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 113, 631-642.
Morimoto, K., Fahnestock, M., Racine, R.J., 2004. Kindling and status epilepticus models of epilepsy: rewiring the brain. Progress in neurobiology 73, 1-60.
Nadler, J.V., Perry, B.W., Cotman, C.W., 1978. Intraventricular kainic acid preferentially destroys hippocampal pyramidal cells. Nature 271, 676-677.
Nakano, N., Nakai, Y., Seo, T.B., Yamada, Y., Ohno, T., Yamanaka, A., Nagai, Y., Fukushima, M., Suzuki, Y., Nakatani, T., Ide, C., 2010. Characterization of conditioned medium of cultured bone marrow stromal cells. Neuroscience letters 483, 57-61.
Nilsen, K.E., Cock, H.R., 2004. Focal treatment for refractory epilepsy: hope for the future? Brain research. Brain research reviews 44, 141-153.
Nilsson, A., Kanje, M., 2005. Amphiregulin acts as an autocrine survival factor for adult sensory neurons. Neuroreport 16, 213-218.
O'Dell, C.M., Das, A., Wallace, G.t., Ray, S.K., Banik, N.L., 2012. Understanding the basic mechanisms underlying seizures in mesial temporal lobe epilepsy and possible therapeutic targets: a review. Journal of neuroscience research 90, 913-924.
Okazaki, M.M., Evenson, D.A., Nadler, J.V., 1995. Hippocampal mossy fiber sprouting and synapse formation after status epilepticus in rats: visualization after retrograde transport of biocytin. The Journal of comparative neurology 352, 515-534.
Park, D.H., Eve, D.J., Sanberg, P.R., Musso, J., 3rd, Bachstetter, A.D., Wolfson, A., Schlunk, A., Baradez, M.O., Sinden, J.D., Gemma, C., 2010. Increased neuronal proliferation in the dentate gyrus of aged rats following neural stem cell implantation. Stem cells and development 19, 175-180.
Peng, C., Zhou, K., An, S., Yang, J., 2015. The effect of CCL19/CCR7 on the proliferation and migration of cell in prostate cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 36, 329-335.
Pitkanen, A., Sutula, T.P., 2002. Is epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal-lobe epilepsy. The Lancet. Neurology 1, 173-181.
Prehn, J.H., Backhauss, C., Krieglstein, J., 1993. Transforming growth factor-beta 1 prevents glutamate neurotoxicity in rat neocortical cultures and protects mouse neocortex from ischemic injury in vivo. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 13, 521-525.
Racine, R.J., 1972a. Modification of seizure activity by electrical stimulation. I. After-discharge threshold. Electroencephalography and clinical neurophysiology 32, 269-279.
Racine, R.J., 1972b. Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol 32, 281-294.
Rao, M.S., Hattiangady, B., Reddy, D.S., Shetty, A.K., 2006. Hippocampal neurodegeneration, spontaneous seizures, and mossy fiber sprouting in the F344 rat model of temporal lobe epilepsy. J Neurosci Res 83, 1088-1105.
Reekmans, K., Praet, J., Daans, J., Reumers, V., Pauwels, P., Van der Linden, A., Berneman, Z.N., Ponsaerts, P., 2012. Current challenges for the advancement of neural stem cell biology and transplantation research. Stem cell reviews 8, 262-278.
Rigau, V., Morin, M., Rousset, M.C., de Bock, F., Lebrun, A., Coubes, P., Picot, M.C., Baldy-Moulinier, M., Bockaert, J., Crespel, A., Lerner-Natoli, M., 2007. Angiogenesis is associated with blood-brain barrier permeability in temporal lobe epilepsy. Brain : a journal of neurology 130, 1942-1956.
Rogawski, M.A., Loscher, W., 2004. The neurobiology of antiepileptic drugs. Nature reviews. Neuroscience 5, 553-564.
Roper, S.N., Steindler, D.A., 2013. Stem cells as a potential therapy for epilepsy. Experimental neurology 244, 59-66.
Ruschenschmidt, C., Koch, P.G., Brustle, O., Beck, H., 2005. Functional properties of ES cell-derived neurons engrafted into the hippocampus of adult normal and chronically epileptic rats. Epilepsia 46 Suppl 5, 174-183.
Schmidt, D., Loscher, W., 2003. How effective is surgery to cure seizures in drug-resistant temporal lobe epilepsy? Epilepsy research 56, 85-91.
Schweitzer, J.S., Patrylo, P.R., Dudek, F.E., 1992. Prolonged field bursts in the dentate gyrus: dependence on low calcium, high potassium, and nonsynaptic mechanisms. Journal of neurophysiology 68, 2016-2025.
Seifert, G., Steinhauser, C., 2013. Neuron-astrocyte signaling and epilepsy. Experimental neurology 244, 4-10.
Sharma, A.K., Reams, R.Y., Jordan, W.H., Miller, M.A., Thacker, H.L., Snyder, P.W., 2007. Mesial temporal lobe epilepsy: pathogenesis, induced rodent models and lesions. Toxicologic pathology 35, 984-999.
Shetty, A.K., 2012. Neural Stem Cell Therapy for Temporal Lobe Epilepsy. In: Noebels, J.L., Avoli, M., Rogawski, M.A., Olsen, R.W., Delgado-Escueta, A.V. (Eds.), Jasper's Basic Mechanisms of the Epilepsies, Bethesda (MD).
Shetty, A.K., Hattiangady, B., 2007. Concise review: prospects of stem cell therapy for temporal lobe epilepsy. Stem cells 25, 2396-2407.
Shetty, A.K., Turner, D.A., 1995. Intracerebroventricular kainic acid administration in adult rat alters hippocampal calbindin and non-phosphorylated neurofilament expression. The Journal of comparative neurology 363, 581-599.
Shetty, A.K., Turner, D.A., 1997. Fetal hippocampal cells grafted to kainate-lesioned CA3 region of adult hippocampus suppress aberrant supragranular sprouting of host mossy fibers. Experimental neurology 143, 231-245.
Shetty, A.K., Turner, D.A., 2000. Fetal hippocampal grafts containing CA3 cells restore host hippocampal glutamate decarboxylase-positive interneuron numbers in a rat model of temporal lobe epilepsy. The Journal of neuroscience : the official journal of the Society for Neuroscience 20, 8788-8801.
Shetty, A.K., Zaman, V., Shetty, G.A., 2003. Hippocampal neurotrophin levels in a kainate model of temporal lobe epilepsy: a lack of correlation between brain-derived neurotrophic factor content and progression of aberrant dentate mossy fiber sprouting. Journal of neurochemistry 87, 147-159.
Sloviter, R.S., Nilaver, G., 1987. Immunocytochemical localization of GABA-, cholecystokinin-, vasoactive intestinal polypeptide-, and somatostatin-like immunoreactivity in the area dentata and hippocampus of the rat. The Journal of comparative neurology 256, 42-60.
Sombati, S., Delorenzo, R.J., 1995. Recurrent spontaneous seizure activity in hippocampal neuronal networks in culture. Journal of neurophysiology 73, 1706-1711.
Stafstrom, C.E., 1998. The pathophysiology of epileptic seizures: a primer for pediatricians. Pediatrics in review / American Academy of Pediatrics 19, 342-351.
Steinlein, O.K., 2004. Genetic mechanisms that underlie epilepsy. Nature reviews. Neuroscience 5, 400-408.
Sun, D.A., Sombati, S., DeLorenzo, R.J., 2001. Glutamate injury-induced epileptogenesis in hippocampal neurons: an in vitro model of stroke-induced "epilepsy". Stroke; a journal of cerebral circulation 32, 2344-2350.
Sutula, T., 2002. Seizure-Induced Axonal Sprouting: Assessing Connections Between Injury, Local Circuits, and Epileptogenesis. Epilepsy currents / American Epilepsy Society 2, 86-91.
Thirunavukkarasu, K., Miles, R.R., Halladay, D.L., Yang, X., Galvin, R.J., Chandrasekhar, S., Martin, T.J., Onyia, J.E., 2001. Stimulation of osteoprotegerin (OPG) gene expression by transforming growth factor-beta (TGF-beta). Mapping of the OPG promoter region that mediates TGF-beta effects. The Journal of biological chemistry 276, 36241-36250.
Thompson, K.W., 2005. Genetically engineered cells with regulatable GABA production can affect afterdischarges and behavioral seizures after transplantation into the dentate gyrus. Neuroscience 133, 1029-1037.
Tian, G.F., Azmi, H., Takano, T., Xu, Q., Peng, W., Lin, J., Oberheim, N., Lou, N., Wang, X., Zielke, H.R., Kang, J., Nedergaard, M., 2005. An astrocytic basis of epilepsy. Nature medicine 11, 973-981.
Tobias, C.A., Shumsky, J.S., Shibata, M., Tuszynski, M.H., Fischer, I., Tessler, A., Murray, M., 2003. Delayed grafting of BDNF and NT-3 producing fibroblasts into the injured spinal cord stimulates sprouting, partially rescues axotomized red nucleus neurons from loss and atrophy, and provides limited regeneration. Experimental neurology 184, 97-113.
Tsai, P.C., Fu, T.W., Chen, Y.M., Ko, T.L., Chen, T.H., Shih, Y.H., Hung, S.C., Fu, Y.S., 2009. The therapeutic potential of human umbilical mesenchymal stem cells from Wharton's jelly in the treatment of rat liver fibrosis. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 15, 484-495.
Turski, L., Ikonomidou, C., Turski, W.A., Bortolotto, Z.A., Cavalheiro, E.A., 1989. Review: cholinergic mechanisms and epileptogenesis. The seizures induced by pilocarpine: a novel experimental model of intractable epilepsy. Synapse 3, 154-171.
Turski, W.A., Cavalheiro, E.A., Bortolotto, Z.A., Mello, L.M., Schwarz, M., Turski, L., 1984. Seizures produced by pilocarpine in mice: a behavioral, electroencephalographic and morphological analysis. Brain research 321, 237-253.
Turski, W.A., Cavalheiro, E.A., Schwarz, M., Czuczwar, S.J., Kleinrok, Z., Turski, L., 1983. Limbic seizures produced by pilocarpine in rats: behavioural, electroencephalographic and neuropathological study. Behavioural brain research 9, 315-335.
Vercelli, A., Mereuta, O.M., Garbossa, D., Muraca, G., Mareschi, K., Rustichelli, D., Ferrero, I., Mazzini, L., Madon, E., Fagioli, F., 2008. Human mesenchymal stem cell transplantation extends survival, improves motor performance and decreases neuroinflammation in mouse model of amyotrophic lateral sclerosis. Neurobiology of disease 31, 395-405.
Wang, H.S., Hung, S.C., Peng, S.T., Huang, C.C., Wei, H.M., Guo, Y.J., Fu, Y.S., Lai, M.C., Chen, C.C., 2004. Mesenchymal stem cells in the Wharton's jelly of the human umbilical cord. Stem cells 22, 1330-1337.
Wang, N.C., Good, L.B., Marsh, S.T., Treiman, D.M., 2009. EEG stages predict treatment response in experimental status epilepticus. Epilepsia 50, 949-952.
Wei, X., Yang, X., Han, Z.P., Qu, F.F., Shao, L., Shi, Y.F., 2013. Mesenchymal stem cells: a new trend for cell therapy. Acta pharmacologica Sinica 34, 747-754.
White, A.M., Williams, P.A., Ferraro, D.J., Clark, S., Kadam, S.D., Dudek, F.E., Staley, K.J., 2006. Efficient unsupervised algorithms for the detection of seizures in continuous EEG recordings from rats after brain injury. Journal of neuroscience methods 152, 255-266.
Wolf, H.K., Wiestler, O.D., 1993. Surgical pathology of chronic epileptic seizure disorders. Brain pathology 3, 371-380.
Yang, C.C., Shih, Y.H., Ko, M.H., Hsu, S.Y., Cheng, H., Fu, Y.S., 2008. Transplantation of human umbilical mesenchymal stem cells from Wharton's jelly after complete transection of the rat spinal cord. PloS one 3, e3336.
Yilmazer-Hanke, D.M., Wolf, H.K., Schramm, J., Elger, C.E., Wiestler, O.D., Blumcke, I., 2000. Subregional pathology of the amygdala complex and entorhinal region in surgical specimens from patients with pharmacoresistant temporal lobe epilepsy. Journal of neuropathology and experimental neurology 59, 907-920.
Yu, H., Zhang, L., Liu, P., 2015. CXCR7 signaling induced epithelial-mesenchymal transition by AKT and ERK pathways in epithelial ovarian carcinomas. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 36, 1679-1683.
Zhang, X., Cui, S.S., Wallace, A.E., Hannesson, D.K., Schmued, L.C., Saucier, D.M., Honer, W.G., Corcoran, M.E., 2002. Relations between brain pathology and temporal lobe epilepsy. The Journal of neuroscience : the official journal of the Society for Neuroscience 22, 6052-6061.
Zipancic, I., Calcagnotto, M.E., Piquer-Gil, M., Mello, L.E., Alvarez-Dolado, M., 2010. Transplant of GABAergic precursors restores hippocampal inhibitory function in a mouse model of seizure susceptibility. Cell transplantation 19, 549-564.

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