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研究生:張成富
研究生(外文):Cheng-Fu Chang
論文名稱:腦中風的治療:神經滋養因子與高壓氧
論文名稱(外文):Neuroprotective Effects of Glial Cell line-Derived Neurotrophic Factor、Bone Morphogenetic Proteins and Hyperbaric Oxygenation against Stroke
指導教授:林欣榮林欣榮引用關係王昀王昀引用關係劉江川Barry J. Hoffer
學位類別:博士
校院名稱:國防醫學院
系所名稱:醫學科學研究所
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:2001
畢業學年度:90
語文別:英文
論文頁數:76
中文關鍵詞:腦缺血膠質細胞神經滋養因子骨成形蛋白質高壓氧甲基安非他命細胞凋亡膠質細胞神經滋養因子受體
外文關鍵詞:Cerebral IschemiaGlial Cell line-Derived Neurotrophic FactorBone Morphogenetic ProteinHyperbaric OxygenationMethamphetamineApoptosisGFR
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本論文研究以使用腦中風的動物模型探討局部腦梗塞 (focal cerebral ischemia)的治療與其機轉。而研究主要的重點在針對神經滋養因子 (neurotrophic factors) 中Transforming Growth Factor-b (TGF-b)家族對於局部腦梗塞的病生理變化的影響,以供臨床治療腦中風病患的參考。
第一個研究課題在探討腦缺血後是否會產生內生性膠質細胞神經滋養因子 (Glial cell line-Derived Neurotrophic Factor; GDNF) 的表現。以往的研究顯示,由外在給予動物腦內 GDNF 可以減輕腦缺血後動物腦梗塞的大小,而 GDNF 的作用在透過與其受體 (GDNF-family receptor alpha-1 ; GFRa-1) 結合後和另一蛋白質 c-RET 所產生。 因此我們在本實驗研究中首先檢測動物腦缺血後腦中 GFRa-1 與 c-RET 的表現。
我們在麻醉動物上進行右側中大腦動脈結紮,使其支配的腦組織區域暫時缺血,90分鐘後再釋放結紮使之產生再灌流傷害 (reperfusion injury)。之後,依再灌流傷害的時間,於0、6、12 與 24 小時後犧牲動物,以 in situ hybridization 方法進行GFRa-1 與 c-RET mRNA 的測定。我們發現GFRa-1 mRNA 在腦缺血後於海馬迴的CA3區,齒狀迴(dentate gyrus;DG) 區 ,腦皮質區 (cortex) 與紋狀體區 (striatum) 都有增加的現象。在齒狀迴區中,GFRa-1 mRNA的表現於6小時後最高。在CA3區,GFRa-1 mRNA的表現為逐漸增加的趨勢。在腦皮質區中,為一直持續的表現,而在0 與24小時分別出現表現的高峰。在紋狀體區中,則是於0小時表現最高。另外,在c-RET mRNA 的表現,我們發現在紋狀體中,於0 小時就已經增加而在 6、 12、24 小時則是逐漸的增加。
綜合我們的結果發現,缺血後腦組織中GFRa-1 與 c-RET都會增加,其增加的程度受再灌流的時間之不同而表現不一。因為GDNF具有神經保護作用,在腦缺血後其受體蛋白質GFR-a1 及c-RET的表現增加,可加強GDNF的神經保護反應(responsiveness)。我們也發現在不同的腦區域中,GFRa-1及c-RET mRNA的增加也有所不同,顯示GDNF對腦中風的神經保護作用因不同的腦區域而有不同。這些結果可以說明在腦缺血後可以引發內生性GDNF的神經保護機轉。
TGF-b家族中還有另外一種主要的滋養因子,骨成形蛋白質(Bone Morphogenetic Protein,簡名BMP)。其中的BMP-6及其受體mRNA,存在於動物胚胎期與成年期的腦內。成年動物在腦受傷後,也會引發BMP-6 受體mRNA表現增加,這些現象表示BMP-6 在腦缺血後的神經保護也佔有一席之地。因此在我們第二個研究課題中,便是探討BMP-6是否在體內與體外可以提供神經保護的作用。我們發現事前給予BMP-6可以減輕H2O2對初級神經細胞培養的毒性作用;BMP-6也可以對抗H2O2減少神經細胞密度的作用。在體內的研究中,我們在動物腦缺血手術之前先給予BMP-6腦內注射 (intracerebral injection),我們發現BMP-6並不改變腦血流量,但是卻造成腦梗塞面積的減少,並且改善動物的運動功能。利用組織細胞化學研究,我們發現BMP-6減少腦缺血後Caspase-3與TUNEL活性。這些結果顯示,BMP-6的神經保護作用可能透過抑制細胞凋亡(apoptosis)的機轉而完成。
我們在第三個研究課題中探討對於急性腦中風的另外一種治療方式:高壓氧治療(Hyperbaric Oxygenation; HBO)。在動物實行腦缺血手術後,我們分別給予:(1)立即高壓氧治療、(2)延遲高壓氧治療、(3)立即高壓空氣治療(Hyperbaric Pressure; HBP)、(4)延遲高壓空氣治療、(5)或正常壓力空氣。結果我們發現,給予正常空氣或延遲高壓空氣治療對腦中風沒有治療效果。在給予延遲高壓空氣治療後,雖然使動物神經功能有恢復的趨勢,但是並不能有效減少腦梗塞的大小。反觀,給予立即高壓氧治療或腦缺血 後60分鐘給予高壓氧治療,卻可以有效減少腦梗塞的大小,並且使動物的神經功能測試得以進步。此研究進一步提供我們另一項可以立即使用在臨床急性腦中風病患的輔助治療方式。
以往的研究顯示,甲基安非他命(Methamphetamine; MA)與腦缺血都可以使過氧化物(reactive oxygen species)的生成增加,進而活化細胞凋亡的途徑而使腦傷害增加。本論文的最後一個研究重點,在探討神經滋養因子GDNF、腦缺血傷害、甲基安非他命、與細胞凋亡之間的關係。我們發現動物在腦缺血手術前給予甲基安非他命會增加腦中的嚴重度。分別給予動物甲基安非他命或只有腦缺血手術,都使腦中細胞凋亡前分子(pro-apoptotic molecule) p53的mRNA增加,而且甲基安非他命對腦缺血增加p53 mRNA的程度有加成的作用。另外,給予甲基安非他命使腦中GDNF含量減少,而事前給予動物GDNF可以對抗甲基安非他命對腦缺血傷害的加成作用。綜合這個研究課題的結果,甲基安非他命可能透過降低內生性GDNF的神經保護作用,及增加細胞凋亡的機轉,因而加強了腦缺血的傷害。
總結,由本論文的研究結果,我們可以得知細胞凋亡在缺血後的腦損傷延伸中扮演一項重要角色。也說明了內生性GDNF為提供腦缺血後神經保護的作用機轉。我們的研究結果更進一步說明了,TGF-b家族的神經滋養因子,在急性腦中風預防與治療上的角色。
This dissertation research focused on focal cerebral ischemia, using the middle cerebral artery occlusion model in rats and mice. Studies were conducted primarily to examine influences of TGF-β family trophic factors on the sequalae of pathophysiological events.
One study examined changes in the receptor for GDNF to test the hypothesis of an endogenous GDNF neuroprotective system.(Time Course Study of GFRa-1 Expression in an Animal Model of Stroke. Sarabi A, Chang CF, Wang Y, Hoffer BJ, and Morales M. Exp Neurol. 2001;170:283-289.) Previous studies have shown that intracerebral administration of glial cell line-derived neurotrophic factor (GDNF) reduces ischemia-mediated cerebral infarction. The biological effects of GDNF are mediated by GDNF-family receptor alpha-1 (GFRa-1) and c-Ret. In this study, we examined the levels of expression of GFRa-1 and c-Ret in a rat model of stroke. Adult Sprague-Dawley rats were anesthetized with chloral hydrate. The right middle cerebral artery was ligated at its distal branch for 90 min. Animals were sacrificed at 0, 6, 12, and 24 h after reperfusion and levels of expression of GFRa-1 and c-Ret mRNA were determined by in situ hybridization histochemistry. We found that GFRa-1 mRNA was up-regulated in CA3, dentate gyrus (DG), cortex, and striatum. The peak of up-regulation in DG was 6 h after reperfusion. GFRa-1 mRNA levels in CA3 were gradually up-regulated over the 24-h reperfusion period. In cortex, GFRa-1 mRNA was up-regulated at all time points; however, the peak of up-regulation was observed at 0 and 24 h after reperfusion. In striatum, an initial up-regulation of GFRa-1 was found at 0 h after ischemia. In striatum, up-regulation of c-Ret mRNA was detected as early as 0 h after reperfusion. A gradual increase was found at 6, 12, and 24 h after reperfusion. In conclusion, our results indicate that there are both regional and temporal differences in up-regulation of GFRa-1 and c-Ret after ischemia. Since GDNF is neuroprotective, up-regulation of GFRa-1 and c-Ret could enhance the responsiveness to GDNF and reduce neuronal damage. The selective up-regulation of GFRa-1 and c-Ret in different brain areas suggests that there may be regional differences in GDNF-induced neuroprotection in stroke. These changes in receptors for GDNF supports the hypothesis of an endogenous GDNF neuroprotective mechanism and extends earlier data showing a parallel upregulation of GDNF itself in stroke.
A second study investigated another member of the TGF-β family, termed Bone Morphogenic Protein-6 (BMP-6) in this same rat model of focal ischemia. (Bone Morphogenetic Protein-6 Reduces Ischemia-Induced Brain Damage in Rats. Wang Y, Chang CF, Morales M, Chou J, Chen H-L, Chiang Y-H, Lin S-Z, Cadet J L, Deng X, Wang, J-Y, Chen, S-Y , Kaplan PL, and Hoffer,BJ. Stroke. 2001;32:2170-2178.) Bone morphogenetic protein-6 (BMP-6) and its receptors are expressed in adult and fetal brain.Receptors for BMP-6 are upregulated in adult brain after injury, leading to the suggestion that BMP-6 is involved in the physiological response to neuronal injury. The purpose of my study was to determine whether there was a neuroprotective effect of BMP-6 in vivo and in vitro. Lactate dehydrogenase and microtubule-associated protein-2 (MAP-2) activities were used to determine the protective effect of BMP-6 against H2O2 in primary cortical cultures. The neuroprotective effects of BMP-6 were also studied in chloral hydrate—anesthetized rats. BMP-6 or vehicle was injected into right cerebral cortex before transient right middle cerebral artery (MCA) ligation. Animals were killed for triphenyl-tetrazolium chloride staining, caspase-3 immunoreactivity and enzymatic assays, and TUNEL assay. A subgroup of animals were used for locomotor behavioral assays.
Application of H2O2 increased lactate dehydrogenase activity and decreased the density of MAP-2 neurons in culture. Both responses were attenuated by BMP-6 pretreatment. Complementary in vivo studies showed that pretreatment with BMP-6 increased motor performance and generated less cerebral infarction induced by MCA ligation/reperfusion in rats. Pretreatment with BMP-6 did not alter cerebral blood flow or physiological parameters. There was decreased ischemia-induced caspase-3 immunoreactivity, caspase-3 enzymatic activity, and density of TUNEL-positive cells in ischemic cortex in BMP6-treated animals. BMP-6 thus reduces ischemia/reperfusion injury, perhaps by attenuating molecular events underlying apoptosis. Because GDNF and BMP-6 utilize entirely different receptors and intracellular second messengers, these experiments also suggest a “cocktail” of trophic factors may provide optimal neuroprotection in stroke.
A third study examined another approach to provide neuroprotection for cerebral ischemia, utilizing hyperbaric oxygen. (Hyperbaric oxygen therapy for treatment of postischemic stroke in adult rats. Chang CF, Niu KC, Hoffer BJ, Wang Y, and Borlongan CV. Exp Neurol. 2000;166:298-306.) The hypothesized efficacy of hyperbaric oxygen (HBO) therapy for treatment of stroke was tested in this study. Adult rats were subjected to occlusion of the middle cerebral artery and subsequently exposed to HBO (3 atm, 2 x 90 min at a 24-h intervals. Animals terminated shortly after the second HBO treatment) or hyperbaric pressure (HBP; 3 atm, 2 x 90 min at a 24-h interval; animals terminated shortly after the second treatment) immediately after the ischemia or after a 60-min delay generally displayed recovery from motor deficits at 2.5 and 24 h of reperfusion. There was also a reduction in cerebral infarction at 24 h of reperfusion compared to ischemic animals subjected to normal atmospheric pressure. While both HBO and HBP treatments promoted beneficial effects, HBO produced more consistent protection than HBP. Treatment with HBO immediately or 60 min after reperfusion produced equally significant attenuations of both cerebral infarction and motor deficits. In contrast, protective effects of HBP treatment against ischemia were noted only when administered immediately after ischemia; there was a significantly reduced infarction volume, but only a trend toward decreased behavioral deficits. The present results demonstrate that HBO and, to some extent HBP, reduce ischemic brain damage and behavioral dysfunctions. Thus, we have validated the use of HBO in clinical situations after acute stroke.
The last study in this thesis examined the mechanisms of methamphetamine facilitation of ischemic cerebral injury. (Methamphetamine potentiates ischemia/reperfusion insults after transient middle cerebral artery ligation.Wang Y, Hayashi T, Chang CF, Chiang YH, Tsao LI, Su TP, Borlongan C, and Lin SZ. Stroke. 2001;32:775-82.) Previous studies have indicated that both methamphetamine (MA) and ischemia/reperfusion injuries involve reactive oxygen species formation and activation of apoptotic mechanisms. That MA could have a synergistic or additive effect with stroke-induced brain damage is possible. The purpose of the present study was to investigate whether administration of MA in vivo would potentiate ischemic brain injury. Adult CD-1 mice were pretreated with MA or saline. Each animal was later anesthetized with chloral hydrate and placed in a stereotaxic frame. A subset of animals received intracerebral administration of GDNF. The right middle cerebral artery and bilateral carotids were transiently occluded for 45 minutes. Regional cerebral blood flow was measured by laser Doppler. Animals were sacrificed for triphenyltetrazolium chloride staining and p53 mRNA Northern blot assay after 24 hours of reperfusion. Cortical and striatal GDNF levels were assayed by ELISA.
We found that pretreatment with MA increased ischemia-induced cerebral infarction. Ischemia or MA alone enhanced p53 (a pro-apoptotic molecule) mRNA expression. Moreover, MA potentiated expression of p53 mRNA in the ischemic mouse brain. MA pretreatment decreased GDNF levels in ischemic striatum. Intracerebral administration of GDNF before ischemia reduced MA-facilitated infarction. Our data indicate that MA exacerbates ischemic insults in brain, perhaps through the inhibition of GDNF-mediated pathways and suggest that MA may antagonize endogenous neuroprotective pathways as part of its mechanism of action. In addition, MA may also upregulate pro-apoptotic mechanisms, contributing to the ultimate extent of infarction.
Taken together, these studies strengthen the hypothesis that apoptotic mechanisms are important in determining the extent of infarction after focal cerebral ischemia. They further provide a preclinical basis for exploring new potential therapies based on trophic proteins, particularly in the TGF-β family.
頁次
目 錄……………………………… I
表次目錄……………………………… II
圖次目錄...……………………………. III
附錄目錄……………………………… V
中文摘要……………………………… VI
英文摘要..……………………………... X
第一章 緒言…………………………. 1
第二章 材料與方法…………………. 9
第三章 結果………………………… 19
第四章 討論………………………… 28
第五章 結論………………………… 35
第六章 參考文獻…………………… 63
附錄…………………………………... 76
1. Abe, K. and Hayashi, T. Expression of the Glial Cell Line-Derived Neurotrophic Factor Gene in Rat Brain After Transient MCA Occlusion. Brain Res. 776; 230-234, 1997.
2. Abe, K., Hayashi, T., and Itoyama, Y. Amelioration of Brain Edema by Topical Application of Glial Cell Line-Derived Neurotrophic Factor in Reperfused Rat Brain. Neurosci.Lett. 231; 37-40, 1997.
3. Albers, G. W., Bates, V. E., Clark, W. M., Bell, R., Verro, P., and Hamilton, S. A. Intravenous Tissue-Type Plasminogen Activator for Treatment of Acute Stroke: the Standard Treatment With Alteplase to Reverse Stroke (STARS) Study. JAMA 283; 1145-1150, 2000.
4. Alder, J., Lee, K. J., Jessell, T. M., and Hatten, M. E. Generation of Cerebellar Granule Neurons in Vivo by Transplantation of BMP-Treated Neural Progenitor Cells. Nat.Neurosci. 2; 535-540, 1999.
5. Alexianu, M. E., Robbins, E., Carswell, S., and Appel, S. H. 1Alpha, 25 Dihydroxyvitamin D3-Dependent Up-Regulation of Calcium-Binding Proteins in Motoneuron Cells. J.Neurosci.Res. 51; 58-66, 1998.
6. Aronowski, J., Samways, E., Strong, R., Rhoades, H. M., and Grotta, J. C. An Alternative Method for the Quantitation of Neuronal Damage After Experimental Middle Cerebral Artery Occlusion in Rats: Analysis of Behavioral Deficit. J.Cereb.Blood Flow Metab 16; 705-713, 1996.
7. Astrup, J., Siesjo, B. K., and Symon, L. Thresholds in Cerebral Ischemia - the Ischemic Penumbra. Stroke 12; 723-725, 1981.
8. Ata, K. A., Lennmyr, F., Funa, K., Olsson, Y., and Terent, A. Expression of Transforming Growth Factor-Beta1, 2, 3 Isoforms and Type I and II Receptors in Acute Focal Cerebral Ischemia: an Immunohistochemical Study in Rat After Transient and Permanent Occlusion of Middle Cerebral Artery. Acta Neuropathol. (Berl) 97; 447-455, 1999.
9. Barone, F. C., White, R. F., Spera, P. A., Ellison, J., Currie, R. W., Wang, X., and Feuerstein, G. Z. Ischemic Preconditioning and Brain Tolerance: Temporal Histological and Functional Outcomes, Protein Synthesis Requirement, and Interleukin-1 Receptor Antagonist and Early Gene Expression. Stroke 29; 1937-1950, 1998.
10. Bederson, J. B., Pitts, L. H., Germano, S. M., Nishimura, M. C., Davis, R. L., and Bartkowski, H. M. Evaluation of 2,3,5-Triphenyltetrazolium Chloride As a Stain for Detection and Quantification of Experimental Cerebral Infarction in Rats. Stroke 17; 1304-1308, 1986.
11. Bird,A. D. and Telfer, A. B. Effect of Hyperbaric Oxygen on Limb Circulation. Lancet. 13; 355-356, 1965.
12. Birling, M. C. and Price, J. Influence of Growth Factors on Neuronal Differentiation. Curr.Opin.Cell Biol. 7; 878-884, 1995.
13. Borlongan, C. V., Martinez, R., Shytle, R. D., Freeman, T. B., Cahill, D. W., and Sanberg, P. R. Striatal Dopamine-Mediated Motor Behavior Is Altered Following Occlusion of the Middle Cerebral Artery. Pharmacol.Biochem.Behav. 52; 225-229, 1995.
14. Bouma S, Mensch MH, Kamermans F, Stern HM, and AAlderen WV. Life Without Blood. Nederl.T.Geneesk. 104; 949-954, 1960.
15. Brown, R. D., Whisnant, J. P., Sicks, J. D., O''Fallon, W. M., and Wiebers, D. O. Stroke Incidence, Prevalence, and Survival: Secular Trends in Rochester, Minnesota, Through 1989. Stroke 27; 373-380, 1996.
16. Brummelkamp, W. H., BOEREMA, I., and HOOGENDYK, L. Treatment of Clostridial Infections With Hyperbaric Oxygen Drenching. A Report on 26 Cases. Lancet 1; 235-238, 1963.
17. Brustovetsky, N. and Dubinsky, J. M. Dual Responses of CNS Mitochondria to Elevated Calcium. J.Neurosci. 20; 103-113, 2000.
18. Buras, J.A. Basic Mechanisms of Hyperbaric Oxygen in the Treatment of Ischemia-Reperfusion Injury. Int.Anesthesiol.Clin. 38; 91-109, 2000.
19. Buras, J.A., Stahl, G. L., Svoboda, K. K., and Reenstra, W. R. Hyperbaric Oxygen Downregulates ICAM-1 Expression Induced by Hypoxia and Hypoglycemia: the Role of NOS. Am.J.Physiol.Cell Physiol. 278; C292-C302, 2000.
20. Burchell, S. A., Ho, H. C., Yu, M., and Margulies, D. R. Effects of Methamphetamine on Trauma Patients: a Cause of Severe Metabolic Acidosis? Crit Care Med. 28; 2112-2115, 2000.
21. Burt, J. T., Kapp, J. P., and Smith, R. R. Hyperbaric Oxygen and Cerebral Infarction in the Gerbil. Surg.Neurol. 28; 265-268, 1987.
22. Calabresi, P., Centonze, D., Gubellini, P., Marfia, G. A., Pisani, A., Sancesario, G., and Bernardi, G. Synaptic Transmission in the Striatum: From Plasticity to Neurodegeneration. Prog.Neurobiol. 61; 231-265, 2000.
23. Carlisle, R., Lanphier, E.H., and Rahn, H. Hyperbaric Oxygen And AND Persistence of Vision in Retinal Ischemia. J. Appl. Physiol. 19; 914-918, 1964.
24. Cerruti, C., Sheng, P., Ladenheim, B., Epstein, C. J., and Cadet, J. L. Involvement of Oxidative and L-Arginine-NO Pathways in the Neurotoxicity of Drugs of Abuse in Vitro. Clin.Exp.Pharmacol.Physiol 22; 381-382, 1995.
25. Charytoniuk, D. A., Traiffort, E., Pinard, E., Issertial, O., Seylaz, J., and Ruat, M. Distribution of Bone Morphogenetic Protein and Bone Morphogenetic Protein Receptor Transcripts in the Rodent Nervous System and Up-Regulation of Bone Morphogenetic Protein Receptor Type II in Hippocampal Dentate Gyrus in a Rat Model of Global Cerebral Ischemia. Neuroscience 100; 33-43, 2000.
26. Chen, R. W., Saunders, P. A., Wei, H., Li, Z., Seth, P., and Chuang, D. M. Involvement of Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) and P53 in Neuronal Apoptosis: Evidence That GAPDH Is Upregulated by P53. J.Neurosci. 19; 9654-9662, 1999.
27. Chen, S. T., Hsu, C. Y., Hogan, E. L., Maricq, H., and Balentine, J. D. A Model of Focal Ischemic Stroke in the Rat: Reproducible Extensive Cortical Infarction. Stroke 17; 738-743, 1986.
28. Cheng, Y., Deshmukh, M., D''Costa, A., Demaro, J. A., Gidday, J. M., Shah, A., Sun, Y., Jacquin, M. F., Johnson, E. M., and Holtzman, D. M. Caspase Inhibitor Affords Neuroprotection With Delayed Administration in a Rat Model of Neonatal Hypoxic-Ischemic Brain Injury. J.Clin.Invest 101; 1992-1999, 1998.
29. Chiang, Y. H., Lin, S. Z., Borlongan, C. V., Hoffer, B. J., Morales, M., and Wang, Y. Transplantation of Fetal Kidney Tissue Reduces Cerebral Infarction Induced by Middle Cerebral Artery Ligation. J.Cereb.Blood Flow Metab 19; 1329-1335, 1999.
30. Contreras, F. L., Kadekaro, M., and Eisenberg, H. M. The Effect of Hyperbaric Oxygen on Glucose Utilization in a Freeze-Traumatized Rat Brain. J.Neurosurg. 68; 137-141, 1988.
31. Corkill, G., Van Housen, K., Hein, L., and Reitan, J. Videodensitometric Estimation of the Protective Effect of Hyperbaric Oxygen in the Ischemic Gerbil Brain. Surg.Neurol. 24; 206-210, 1985.
32. de Viragh, P. A., Haglid, K. G., and Celio, M. R. Parvalbumin Increases in the Caudate Putamen of Rats With Vitamin D Hypervitaminosis. Proc.Natl.Acad.Sci U.S.A 86; 3887-3890, 1989.
33. Dennog, C., Radermacher, P., Barnett, Y. A., and Speit, G. Antioxidant Status in Humans After Exposure to Hyperbaric Oxygen. Mutat.Res. 428; 83-89, 1999.
34. Ebisawa, T., Tada, K., Kitajima, I., Tojo, K., Sampath, T. K., Kawabata, M., Miyazono, K., and Imamura, T. Characterization of Bone Morphogenetic Protein-6 Signaling Pathways in Osteoblast Differentiation. J.Cell Sci. 112; 3519-3527, 1999.
35. Endres, M., Namura, S., Shimizu-Sasamata, M., Waeber, C., Zhang, L., Gomez-Isla, T., Hyman, B. T., and Moskowitz, M. A. Attenuation of Delayed Neuronal Death After Mild Focal Ischemia in Mice by Inhibition of the Caspase Family. J.Cereb.Blood Flow Metab 18; 238-247, 1998.
36. Fenton, L. H. and Robinson, M. B. Repeated Exposure to Hyperbaric Oxygen Sensitizes Rats to Oxygen-Induced Seizures. Brain Res. 632; 143-149, 1993.
37. Fitzpatrick, D. T. Hyperbaric Oxygen Therapy. Mo.Med. 91; 684-689, 1994.
38. Galter, D., Bottner, M., Krieglstein, K., Schomig, E., and Unsicker, K. Differential Regulation of Distinct Phenotypic Features of Serotonergic Neurons by Bone Morphogenetic Proteins. Eur.J.Neurosci. 11; 2444-2452, 1999.
39. Gazzaniga, M. S., Bogen, J. E., and Sperry, R. W. Observations on Visual Perception After Disconnexion of the Cerebral Hemispheres in Man. Brain 88; 221-236, 1965.
40. Giusti, P., Ducic, I., Puia, G., Arban, R., Walser, A., Guidotti, A., and Costa, E. Imidazenil: a New Partial Positive Allosteric Modulator of Gamma-Aminobutyric Acid (GABA) Action at GABAA Receptors. J.Pharmacol.Exp.Ther. 266; 1018-1028, 1993.
41. Glazner, G. W., Mu, X., and Springer, J. E. Localization of Glial Cell Line-Derived Neurotrophic Factor Receptor Alpha and C-Ret MRNA in Rat Central Nervous System. J.Comp Neurol. 391; 42-49, 1998.
42. Grabowski, M., Brundin, P., and Johansson, B. B. Paw-Reaching, Sensorimotor, and Rotational Behavior After Brain Infarction in Rats. Stroke 24; 889-895, 1993.
43. Harabin, A. L., Braisted, J. C., and Flynn, E. T. Response of Antioxidant Enzymes to Intermittent and Continuous Hyperbaric Oxygen. J.APPL.PHYSIOL. 69; 328-335, 1990.
44. Hart, G. B. Treatment of Decompression Illness and Air Embolism With Hyperbaric Oxygen. Aerosp.Med. 45; 1190-1193, 1974.
45. Hayashi, T., Hirata, H., Asanuma, M., Ladenheim, B., Tsao, L. I., Cadet, J. L., and Su, T. P. Delta Opioid Peptide [D-Ala2, D-Leu5]Enkephalin Causes a Near Complete Blockade of the Neuronal Damage Caused by a Single High Dose of Methamphetamine: Examining the Role of P53. Synapse 39; 305-312, 2001.
46. Heros, R. C., Camarata, P. J., and Latchaw, R. E. Brain Attack. Introduction. Neurosurg.Clin.N.Am. 8; 135-144, 1997.
47. Heyman, A., Saltzman, H. A., and Whalen, R. E. The Use of Hyperbaric Oxygenation in the Treatment of Cerebral Ischemia and Infarction. Circulation 33; II20-II27, 1966.
48. Hirata, H. and Cadet, J. L. P53-Knockout Mice Are Protected Against the Long-Term Effects of Methamphetamine on Dopaminergic Terminals and Cell Bodies. J.Neurochem. 69; 780-790, 1997.
49. Hoffer, B. J., Hoffman, A., Bowenkamp, K., Huettl, P., Hudson, J., Martin, D., Lin, L. F., and Gerhardt, G. A. Glial Cell Line-Derived Neurotrophic Factor Reverses Toxin-Induced Injury to Midbrain Dopaminergic Neurons in Vivo. Neurosci.Lett. 182; 107-111, 1994.
50. Holbach, K. H., Caroli, A., and Wassmann, H. Cerebral Energy Metabolism in Patients With Brain Lesions of Normo- and Hyperbaric Oxygen Pressures. J.Neurol. 217; 17-30, 1977.
51. Ingvar DH and Lassen NA. Treatment of Focal Cerebral Ischemia With Hyperbaric Oxygen:Report of 4 Cases. Acta Neurol.Scand. 41; 92-95, 1965.
52. Ito, T., Yufu, K., Mori, A., and Packer, L. Oxidative Stress Alters Arginine Metabolism in Rat Brain: Effect of Sub-Convulsive Hyperbaric Oxygen Exposure. Neurochem.Int. 29; 187-195, 1996.
53. Jabaudon, D., Scanziani, M., Gahwiler, B. H., and Gerber, U. Acute Decrease in Net Glutamate Uptake During Energy Deprivation. Proc.Natl.Acad.Sci U.S.A 97; 5610-5615, 2000.
54. Jordan, J., Bottner, M., Schluesener, H. J., Unsicker, K., and Krieglstein, K. Bone Morphogenetic Proteins: Neurotrophic Roles for Midbrain Dopaminergic Neurons and Implications of Astroglial Cells. Eur.J.Neurosci. 9; 1699-1709, 1997.
55. Katzan, I. L., Furlan, A. J., Lloyd, L. E., Frank, J. I., Harper, D. L., Hinchey, J. A., Hammel, J. P., Qu, A., and Sila, C. A. Use of Tissue-Type Plasminogen Activator for Acute Ischemic Stroke: the Cleveland Area Experience. JAMA 283; 1151-1158, 2000.
56. Kidwell, C. S., Liebeskind, D. S., Starkman, S., and Saver, J. L. Trends in Acute Ischemic Stroke Trials Through the 20th Century. Stroke 32; 1349-1359, 2001.
57. Kitagawa, H., Hayashi, T., Mitsumoto, Y., Koga, N., Itoyama, Y., and Abe, K. Reduction of Ischemic Brain Injury by Topical Application of Glial Cell Line-Derived Neurotrophic Factor After Permanent Middle Cerebral Artery Occlusion in Rats. Stroke 29; 1417-1422, 1998.
58. Koh, J. Y. and Choi, D. W. Quantitative Determination of Glutamate Mediated Cortical Neuronal Injury in Cell Culture by Lactate Dehydrogenase Efflux Assay. J.Neurosci.Methods 20; 83-90, 1987.
59. Kohshi, K., Yokota, A., Konda, N., Kinoshita, Y., and Kajiwara, H. Intracranial Pressure Responses During Hyperbaric Oxygen Therapy. Neurol.Med.Chir.(Tokyo.) 31; 575-581, 1991.
60. Kokaia, Z., Airaksinen, M. S., Nanobashvili, A., Larsson, E., Kujamaki, E., Lindvall, O., and Saarma, M. GDNF Family Ligands and Receptors Are Differentially Regulated After Brain Insults in the Rat. Eur.J.Neurosci. 11; 1202-1216, 1999.
61. Kunkle, T. D. and Beckman, E. L. Bubble Dissolution Physics and the Treatment of Decompression Sickness. Med.Phys. 10; 184-190, 1983.
62. Lan, K. C., Lin, Y. F., Yu, F. C., Lin, C. S., and Chu, P. Clinical Manifestations and Prognostic Features of Acute Methamphetamine Intoxication. J.Formos.Med.Assoc. 97; 528-533, 1998.
63. Larson, J. L., Stephenson, L. L., and Zamboni, W. A. Effect of Hyperbaric Oxygen on Neutrophil CD18 Expression. Plast.Reconstr.Surg. 105; 1375-1381, 2000.
64. Levin, D., Norman, D., Zinman, C., Rubinstein, L., Sabo, E., Misselevich, I., Reis, D., and Boss, J. H. Treatment of Experimental Avascular Necrosis of the Femoral Head With Hyperbaric Oxygen in Rats: Histological Evaluation of the Femoral Heads During the Early Phase of the Reparative Process. Exp.Mol.Pathol. 67; 99-108, 1999.
65. Lewen, A., Soderstrom, S., Hillered, L., and Ebendal, T. Expression of Serine/Threonine Kinase Receptors in Traumatic Brain Injury. Neuroreport 8; 475-479, 1997.
66. Lin, L. F., Doherty, D. H., Lile, J. D., Bektesh, S., and Collins, F. GDNF: a Glial Cell Line-Derived Neurotrophic Factor for Midbrain Dopaminergic Neurons. Science 260; 1130-1132, 1993.
67. Lin, S. Z., Chiou, A. L., and Wang, Y. Ketamine Antagonizes Nitric Oxide Release From Cerebral Cortex After Middle Cerebral Artery Ligation in Rats. Stroke 27; 747-752, 1996.
68. Lin, S. Z., Hoffer, B. J., Kaplan, P., and Wang, Y. Osteogenic Protein-1 Protects Against Cerebral Infarction Induced by MCA Ligation in Adult Rats. Stroke 30; 126-133, 1999.
69. Longa, E. Z., Weinstein, P. R., Carlson, S., and Cummins, R. Reversible Middle Cerebral Artery Occlusion Without Craniectomy in Rats. Stroke 20; 84-91, 1989.
70. Love, S. Oxidative Stress in Brain Ischemia. Brain Pathol. 9; 119-131, 1999.
71. Mabie, P. C., Mehler, M. F., and Kessler, J. A. Multiple Roles of Bone Morphogenetic Protein Signaling in the Regulation of Cortical Cell Number and Phenotype. J.Neurosci. 19; 7077-7088, 1999.
72. Martin, D. P., Schmidt, R. E., DiStefano, P. S., Lowry, O. H., Carter, J. G., and Johnson, E. M., Jr. Inhibitors of Protein Synthesis and RNA Synthesis Prevent Neuronal Death Caused by Nerve Growth Factor Deprivation. J.Cell Biol. 106; 829-844, 1988.
73. Mattson, M. P. and Cheng, B. Growth Factors Protect Neurons Against Excitotoxic/Ischemic Damage by Stabilizing Calcium Homeostasis. Stroke 24; I136-I140, 1993.
74. Mendzheritskii, A. M., Lysenko, A. V., Uskova, N. I., and Sametskii, E. A. Studies of the Mechanism of the Anticonvulsant Effect of Delta-Sleep-Inducing Peptide in Conditions of Increased Oxygen Tension. Neurosci.Behav.Physiol 27; 714-717, 1997.
75. Menotti, A., Jacobs, D. R., Jr., Blackburn, H., Kromhout, D., Nissinen, A., Nedeljkovic, S., Buzina, R., Mohacek, I., Seccareccia, F., Giampaoli, S., Dontas, A., Aravanis, C., and Toshima, H. Twenty-Five-Year Prediction of Stroke Deaths in the Seven Countries Study: the Role of Blood Pressure and Its Changes. Stroke 27; 381-387, 1996.
76. Mhairi, Macrae, I. New Models of Focal Cerebral Ischaemia. Br.J.Clin.Pharmacol. 34; 302-308, 1992.
77. Mialon, P., Joanny, P., Gibey, R., Cann-Moisan, C., Caroff, J., Steinberg, J., and Barthelemy, L. Amino Acids and Ammonia in the Cerebral Cortex, the Corpus Striatum and the Brain Stem of the Mouse Prior to the Onset and After a Seizure Induced by Hyperbaric Oxygen. Brain Res. 676; 352-357, 1995.
78. Miyazaki, H., Okuma, Y., Fujii, Y., Nagashima, K., and Nomura, Y. Glial Cell Line-Derived Neurotrophic Factor Protects Against Delayed Neuronal Death After Transient Forebrain Ischemia in Rats. Neuroscience 89; 643-647, 1999.
79. Mogami, H., Hayakawa, T., Kanai, N., Kuroda, R., Yamada, R., Ikeda, T., Katsurada, K., and Sugimoto, T. Clinical Application of Hyperbaric Oxygenation in the Treatment of Acute Cerebral Damage. J.Neurosurg. 31; 636-643, 1969.
80. Moore, M. W., Klein, R. D., Farinas, I., Sauer, H., Armanini, M., Phillips, H., Reichardt, L. F., Ryan, A. M., Carver-Moore, K., and Rosenthal, A. Renal and Neuronal Abnormalities in Mice Lacking GDNF. Nature 382; 76-79, 1996.
81. Morales, M. and Bloom, F. E. The 5-HT3 Receptor Is Present in Different Subpopulations of GABAergic Neurons in the Rat Telencephalon. J.Neurosci. 17; 3157-3167, 1997.
82. Mount, H. T., Dean, D. O., Alberch, J., Dreyfus, C. F., and Black, I. B. Glial Cell Line-Derived Neurotrophic Factor Promotes the Survival and Morphologic Differentiation of Purkinje Cells. Proc.Natl.Acad.Sci.U.S.A. 92; 9092-9096, 1995.
83. Muir, J. K. and Ellis, E. F. Acute Cocaine Administration Alters Posttraumatic Blood Pressure and Cerebral Blood Flow in Rats. Am.J.Physiol 268; H68-H73, 1995.
84. Neubauer, R. A. and End, E. Hyperbaric Oxygenation As an Adjunct Therapy in Strokes Due to Thrombosis. A Review of 122 Patients. Stroke 11; 297-300, 1980.
85. Neumann-Haefelin, T., Kastrup, A., de Crespigny, A., Yenari, M. A., Ringer, T., Sun, G. H., and Moseley, M. E. Serial MRI After Transient Focal Cerebral Ischemia in Rats: Dynamics of Tissue Injury, Blood-Brain Barrier Damage, and Edema Formation. Stroke 31; 1965-1972, 2000.
86. Tissue Plasminogen Activator for Acute Ischemic Stroke. The National Institute of Neurological Disorders and Stroke Rt-PA Stroke Study Group. N.Engl.J.Med. 333; 1581-1587, 1995.
87. Rastenyte, D., Cepaitis, Z., Sarti, C., Bluzhas, J., and Tuomilehto, J. Epidemiology of Stroke in Kaunas, Lithuania. First Results From the Kaunas Stroke Register. Stroke 26; 240-244, 1995.
88. Reeben, M., Laurikainen, A., Hiltunen, J. O., Castren, E., and Saarma, M. The Messenger RNAs for Both Glial Cell Line-Derived Neurotrophic Factor Receptors, C-Ret and GDNFRalpha, Are Induced in the Rat Brain in Response to Kainate-Induced Excitation. Neuroscience 83; 151-159, 1998.
89. Reitan, J. A., Kien, N. D., Thorup, S., and Corkill, G. Hyperbaric Oxygen Increases Survival Following Carotid Ligation in Gerbils. Stroke 21; 119-123, 1990.
90. Rothfuss, A., Dennog, C., and Speit, G. Adaptive Protection Against the Induction of Oxidative DNA Damage After Hyperbaric Oxygen Treatment. Carcinogenesis 19; 1913-1917, 1998.
91. Rothrock, J. F., Rubenstein, R., and Lyden, P. D. Ischemic Stroke Associated With Methamphetamine Inhalation. Neurology 38; 589-592, 1988.
92. Russell, G. B., Vance, W. T., and Graybeal, J. M. Attenuation of Midazolam-Induced EEG Activation in Rats by Both Flumazenil and Hyperbaric Oxygen. J.Neurosurg.Anesthesiol. 7; 271-279, 1995.
93. Sakurai, M., Hayashi, T., Abe, K., Yaginuma, G., Meguro, T., Itoyama, Y., and Tabayashi, K. Induction of Glial Cell Line-Derived Neurotrophic Factor and C-Ret Porto-Oncogene-Like Immunoreactivity in Rabbit Spinal Cord After Transient Ischemia. Neurosci.Lett. 276; 123-126, 1999.
94. Saltzman, H. A. Hyperbaric Oxygen in Cardiovascular Disease. Potential Usages and Hazards. Circulation 31; 454-462, 1965.
95. Sanchez, M. P., Silos-Santiago, I., Frisen, J., He, B., Lira, S. A., and Barbacid, M. Renal Agenesis and the Absence of Enteric Neurons in Mice Lacking GDNF. Nature 382; 70-73, 1996.
96. Sarabi, A., Hoffer, B. J., Olson, L., and Morales, M. GFR Alpha-1 Is Expressed in Parvalbumin GABAergic Neurons in the Hippocampus. Brain Res. 877; 262-270, 2000.
97. Sasaki, C., Kitagawa, H., Zhang, W. R., Warita, H., Sakai, K., and Abe, K. Temporal Profile of Cytochrome c and Caspase-3 Immunoreactivities and TUNEL Staining After Permanent Middle Cerebral Artery Occlusion in Rats. Neurol.Res. 22; 223-228, 2000.
98. Shinomiya, N., Suzuki, S., Hashimoto, A., Ito, M., Takaai, Y., and Oiwa, H. Effect of Hyperbaric Oxygen on Intercellular Adhesion Molecule-1 (ICAM-1) Expression in Murine Lung. Aviat.Space.Environ.Med. 69; 1-7, 1998.
99. Smit, A. A., Wieling, W., Voogel, A. J., Koster, R. W., and van Zwieten, P. A. Orthostatic Hypotension Due to Suppression of Vasomotor Outflow After Amphetamine Intoxication. Mayo Clin.Proc. 71; 1067-1070, 1996.
100. Stumm, G., Schlegel, J., Schafer, T., Wurz, C., Mennel, H. D., Krieg, J. C., and Vedder, H. Amphetamines Induce Apoptosis and Regulation of Bcl-x Splice Variants in Neocortical Neurons. FASEB J. 13; 1065-1072, 1999.
101. Tanaka, K., Wada, N., and Ogawa, N. Chronic Cerebral Hypoperfusion Induces Transient Reversible Monoaminergic Changes in the Rat Brain. Neurochem.Res. 25; 313-320, 2000.
102. Tendler, Y., Weisinger, G., Coleman, R., Diamond, E., Lischinsky, S., Kerner, H., Rotter, V., and Zinder, O. Tissue-Specific P53 Expression in the Nervous System. Brain Res.Mol.Brain Res. 72; 40-46, 1999.
103. Thorn, J. J., Kallehave, F., Westergaard, P., Hansen, E. H., and Gottrup, F. The Effect of Hyperbaric Oxygen on Irradiated Oral Tissues: Transmucosal Oxygen Tension Measurements. J.Oral Maxillofac.Surg. 55; 1103-1107, 1997.
104. Tomac, A.C., Lindqvist, E., Lin, L. F., Ogren, S. O., Young, D., Hoffer, B. J., and Olson, L. Protection and Repair of the Nigrostriatal Dopaminergic System by GDNF in Vivo. Nature 373; 335-339, 1995.
105. Tomac, A.C., Grinberg, A., Huang, S. P., Nosrat, C., Wang, Y., Borlongan, C., Lin, S. Z., Chiang, Y. H., Olson, L., Westphal, H., and Hoffer, B. J. Glial Cell Line-Derived Neurotrophic Factor Receptor Alpha1 Availability Regulates Glial Cell Line-Derived Neurotrophic Factor Signaling: Evidence From Mice Carrying One or Two Mutated Alleles. Neuroscience 95; 1011-1023, 2000.
106. Tomizawa, K., Matsui, H., Kondo, E., Miyamoto, K., Tokuda, M., Itano, T., Nagahata, S., Akagi, T., and Hatase, O. Developmental Alteration and Neuron-Specific Expression of Bone Morphogenetic Protein-6 (BMP-6) MRNA in Rodent Brain. Brain Res.Mol.Brain Res. 28; 122-128, 1995.
107. Torbati, D., Lo, P., and Lambertsen, C. J. Local Cerebral Glucose Utilization Rate Following Intermittent Exposures to 2 Atmosphere Absolute Oxygen. Neurosci.Lett. 50; 79-84, 1984.
108. Trupp, M., Belluardo, N., Funakoshi, H., and Ibanez, C. F. Complementary and Overlapping Expression of Glial Cell Line-Derived Neurotrophic Factor (GDNF), C-Ret Proto-Oncogene, and GDNF Receptor-Alpha Indicates Multiple Mechanisms of Trophic Actions in the Adult Rat CNS. J.Neurosci. 17; 3554-3567, 1997.
109. Tsao, L. I., Ladenheim, B., Andrews, A. M., Chiueh, C. C., Cadet, J. L., and Su, T. P. Delta Opioid Peptide [D-Ala2,D-Leu5]Enkephalin Blocks the Long-Term Loss of Dopamine Transporters Induced by Multiple Administrations of Methamphetamine: Involvement of Opioid Receptors and Reactive Oxygen Species. J.Pharmacol.Exp.Ther. 287; 322-331, 1998.
110. Verity, A. N., Wyatt, T. L., Lee, W., Hajos, B., Baecker, P. A., Eglen, R. M., and Johnson, R. M. Differential Regulation of Glial Cell Line-Derived Neurotrophic Factor (GDNF) Expression in Human Neuroblastoma and Glioblastoma Cell Lines. J.Neurosci.Res. 55; 187-197, 1999.
111. Wall, N. A., Blessing, M., Wright, C. V., and Hogan, B. L. Biosynthesis and in Vivo Localization of the Decapentaplegic-Vg-Related Protein, DVR-6 (Bone Morphogenetic Protein-6). J.Cell Biol. 120; 493-502, 1993.
112. Wang, Y., Chiang, Y. H., Su, T. P., Hayashi, T., Morales, M., Hoffer, B. J., and Lin, S. Z. Vitamin D(3) Attenuates Cortical Infarction Induced by Middle Cerebral Arterial Ligation in Rats. Neuropharmacology 39; 873-880, 2000.
113. Wang, Y., Lin, S. Z., Chiou, A. L., Williams, L. R., and Hoffer, B. J. Glial Cell Line-Derived Neurotrophic Factor Protects Against Ischemia-Induced Injury in the Cerebral Cortex. J.Neurosci. 17; 4341-4348, 1997.
114. Warren, J., Sacksteder, M. R., and Thuning, C. A. Oxygen Immunosuppression: Modification of Experimental Allergic Encephalomyelitis in Rodents. J.Immunol. 121; 315-320, 1978.
115. Wei, G., Wu, G., and Cao, X. Dynamic Expression of Glial Cell Line-Derived Neurotrophic Factor After Cerebral Ischemia. Neuroreport 11; 1177-1183, 2000.
116. Weien, R. W. and Baumgartner, N. Altitude Decompression Sickness: Hyperbaric Therapy Results in 528 Cases. Aviat.Space.Environ.Med. 61; 833-836, 1990.
117. Weinstein, P. R., Anderson, G. G., and Telles, D. A. Results of Hyperbaric Oxygen Therapy During Temporary Middle Cerebral Artery Occlusion in Unanesthetized Cats. Neurosurgery 20; 518-524, 1987.
118. Yen, D. J., Wang, S. J., Ju, T. H., Chen, C. C., Liao, K. K., Fuh, J. L., and Hu, H. H. Stroke Associated With Methamphetamine Inhalation. Eur.Neurol. 34; 16-22, 1994.
119. Zamboni, W. A., Roth, A. C., Russell, R. C., Graham, B., Suchy, H., and Kucan, J. O. Morphologic Analysis of the Microcirculation During Reperfusion of Ischemic Skeletal Muscle and the Effect of Hyperbaric Oxygen. Plast.Reconstr.Surg. 91; 1110-1123, 1993.
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