血脑屏障破坏参与癫痫发生机制的研究进展_West China Medical Journal

Authors：

李琼 ,  周东

Corresponding author：

周东, Email: liqiong1982110@126.com

Keywords：

癫痫; 血脑屏障; 星形胶质细胞; 转化生长因子β受体

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【摘要】 　癫痫是神经系统疾病中一种严重危害人类健康的常见病、多发病，常继发于脑的损伤，如外伤、肿瘤、缺血及感染等，目前仍有20%~30%的患者为难治性癫痫，对癫痫发病机制的研究一直是国内和国际神经科学界研究的热点之一。最近研究发现脑外伤患者20％～40％可能出现外伤性癫痫，通过对其发病机制的研究提示血脑屏障破坏对癫痫发生可能有着重要作用，现就血脑屏障破坏参与癫痫发生的具体机制进行综述。

Citation： 李琼,周东. 血脑屏障破坏参与癫痫发生机制的研究进展. West China Medical Journal, 2010, 25(11): 2107-2110. doi: Copy

1.	Tomkins O, shelef I, kaizerman I, et al. Blood-brain barrier disruption in post traumatic epilepsy[J]. J Neurol Neurolsurg Psychiatry, 2008, 79(7): 774-777.
2.	Neuwelt EA. Mechanisms of disease: the blood-brain barrier[J]. Neurosurgery, 2004, 54(1): 131-140.
3.	Janigro D. Blood-brain barrier, ion homeostasis and epilepsy: possible implications towards the understanding of ketogenic diet mechanisms[J]. Epilepsy Res, 1999, 37(3): 223-232.
4.	程基焱, 黄吉春, 高然, 等. 马桑内酯致痫对大鼠突触及血脑屏障超微结构的影响[J]. 四川动物, 2008, 27(3): 382-385.
5.	Solbrig MV, Koob GF. Epilepsy, CNS viral injury and dynorphin[J]. Trends Pharmacol Sci, 2004, 25(2): 98-104.
6.	van Vliet EA, da Costa Araújo S, Redeker S, et al. Blood-brain barrier leakage may lead to progression of temporal lobe epilepsy[J]. Brain, 2007, 130(pt2): 521-534.
7.	Pavlovsky L, Seiffert E, Heinemann U, et al. Persistent BBB disruption may underlie alpha interferon induced seizures[J]. J Neurol, 2005, 252(1): 42-46.
8.	Oby E, Janigro D. The Blood-Brain Barrier and Epilepsy[J]. Epilepsia, 2006, 47(11): 1761-1774.
9.	Ivens S, Kaufer D, Flores LP, et al. TGF-βreceptor-mediated albumin uptake into astrocytes is involved in neocortical Epileptogenesis[J]. Brain, 2007, 130(pt2): 535-547.
10.	Nagy JI, Dudek FE, Rash JE. Update on connexins and gap junctions in neurons and glia in the mammalian nervous system[J]. Brain Res Rev, 2004, 47(1-3): 191-215.
11.	Wallraff A, Khling R, Heinemann U, et al. The impact of astrocytic gap junctional coupling on potassium buffering in the hippocampus[J]. J Neurosci, 2006, 26(20): 5438-5447.
12.	Cacheaux LP, Ivens S, David Y, et al. Transcriptome profiling reveals TGF-β signaling involvement in epileptogenesis[J]. J Neurosci, 2009, 29(28): 8927-8935.
13.	王敏, 郑乃智, 纪萍, 等. 癫痫大鼠海马缝隙连接蛋白43的表达及生胃酮的保护作用[J]. 中风与神经疾病杂志, 2008, 25(5): 540-543.
14.	Rouach N, Koulakoff A, Abudara V, et al. Astroglial metabolic networks sustain hippocampal synaptic transmission[J]. Science, 2008, 322(5907), 1551-1555.
15.	Seifert g, Carmignoto G, Steinhuser C. Astrocyte dysfunction in epilepsy[J]. Brain Res Rev, 2010, 63(1-2): 212-221.
16.	Benarroch EE. Astrocyte-neuron interactions implications for epilepsy[J]. Neurology, 2009, 73(16): 1323-1327.
17.	Friedman A, Kaufer D, Heinemann U. Blood-brain barrier breakdown-inducing astrocytic transformation: novel targets for the prevention of epilepsy[J]. Epilepsy Res, 2009, 85(2-3): 142-149.
18.	Djukic B, Casper KB, Philpot BD, et al. Conditional knock-out of Kir4. 1 leads to glial membrane depolarization, inhibition of potassium and glutamate uptake, and enhanced short-term synaptic potentiation[J]. J Neurosci, 2007, 27(42): 11354-11365.
19.	Seifert G, Schilling K, Steinhuser C. Astrocyte dysfunction in neurological disorders: a molecular perspective[J]. Nat Rev Neurosci, 2006, 7(3): 194-206.
20.	Eid T, Ghosh A, Wang Y, et al. Recurrent seizures and brain pathology after inhibition of glutamine synthetase in the hippocampus in rats[J]. Brain, 2008, 131(pt8), 2061-2070.
21.	Eid T, Thomas MJ, Spencer DD, et al. Loss of glutamine synthetase in the human epileptogenic hippocampus: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy[J]. Lancet, 2004, 363(9402): 28-37.
22.	卫向红, 李正莉, 朱长庚, 等. 激活的星形胶质细胞条件培养液致痫效应及其对大鼠脑内Glu和IL-2 R表达的影响[J]. 中国组织化学与细胞化学杂志, 2007, 16(4): 446-450.
23.	Boison D. Adenosine augmentation therapies (AATs) for epilepsy: Prospect of cell and gene therapies[J]. Epilepsy Res, 2009, 85(2-3): 131-141.
24.	Fedele DE, Gouder N, Guttinger M, et al. Astrogliosis in epilepsy leads to over expression of adenosine kinase, resulting in seizure aggravation[J]. Brain, 2005, 128(10): 2383-2395.
25.	Haspolat S, Mihci E, Coskun M, et al. Interleukin-1β, tumor necrosis factor-a, and nitrite levels in febrile seizures[J]. Child Neurol, 2002, 17(10): 749-751.
26.	Ravizza T, Noé F, Zardoni D, et al. Interleukin Converting Enzyme inhibition impairs kindling epileptogenesis in rats by blocking astrocytic IL-1beta production[J]. Neurobiol Dis, 2008, 31(3): 327-333.
27.	Tian GF, Azmi H, Takano T, et al. An astrocytic basis of epilepsy[J]. Nat Med, 2005, 11(9): 973-981.
28.	Plata-Salaman CR, Ilyin SE, Turrin NP, et al. Kindling modulates the IL-1beta system, TNF-alpha, TGF-beta1, and neuropeptide mRNAs in specific brain regions[J]. Brain Res Mol Brain Res, 2000, 75(2): 248-258.
29.	Morganti-Kossmann MC, Rancan M, Stahel PF, et al. Inflammatory response in acute traumatic brain injury: a double-edged sword[J]. Curr Opin Crit Care, 2002, 8(2): 101-105.
30.	Perillan PR, Chen M, Potts EA, et al. Transforming growth factor-beta 1 regulates Kir2. 3 inward rectifier K+ channels via phospholipase C and protein kinase C-delta in reactive astrocytes from adult rat brain[J]. J Biol Chem, 2002, 277(3): 1974-1980.
31.	Ding G, Jiang Q, Li L, et al. Detection of BBB disruption and hemorrhage by Gd-DTPA enhanced MRI after embolic stroke in rat[J]. Brain Res, 2006, 1114(1): 195-203.

1. 　Tomkins O, shelef I, kaizerman I, et al. Blood-brain barrier disruption in post traumatic epilepsy[J]. J Neurol Neurolsurg Psychiatry, 2008, 79(7): 774-777.
2. 　Neuwelt EA. Mechanisms of disease: the blood-brain barrier[J]. Neurosurgery, 2004, 54(1): 131-140.
3. 　Janigro D. Blood-brain barrier, ion homeostasis and epilepsy: possible implications towards the understanding of ketogenic diet mechanisms[J]. Epilepsy Res, 1999, 37(3): 223-232.
4. 　程基焱, 黄吉春, 高然, 等. 马桑内酯致痫对大鼠突触及血脑屏障超微结构的影响[J]. 四川动物, 2008, 27(3): 382-385.
5. 　Solbrig MV, Koob GF. Epilepsy, CNS viral injury and dynorphin[J]. Trends Pharmacol Sci, 2004, 25(2): 98-104.
6. 　van Vliet EA, da Costa Araújo S, Redeker S, et al. Blood-brain barrier leakage may lead to progression of temporal lobe epilepsy[J]. Brain, 2007, 130(pt2): 521-534.
7. 　Pavlovsky L, Seiffert E, Heinemann U, et al. Persistent BBB disruption may underlie alpha interferon induced seizures[J]. J Neurol, 2005, 252(1): 42-46.
8. 　Oby E, Janigro D. The Blood-Brain Barrier and Epilepsy[J]. Epilepsia, 2006, 47(11): 1761-1774.
9. 　Ivens S, Kaufer D, Flores LP, et al. TGF-βreceptor-mediated albumin uptake into astrocytes is involved in neocortical Epileptogenesis[J]. Brain, 2007, 130(pt2): 535-547.
10. 　Nagy JI, Dudek FE, Rash JE. Update on connexins and gap junctions in neurons and glia in the mammalian nervous system[J]. Brain Res Rev, 2004, 47(1-3): 191-215.
11. 　Wallraff A, Khling R, Heinemann U, et al. The impact of astrocytic gap junctional coupling on potassium buffering in the hippocampus[J]. J Neurosci, 2006, 26(20): 5438-5447.
12. 　Cacheaux LP, Ivens S, David Y, et al. Transcriptome profiling reveals TGF-β signaling involvement in epileptogenesis[J]. J Neurosci, 2009, 29(28): 8927-8935.
13. 　王敏, 郑乃智, 纪萍, 等. 癫痫大鼠海马缝隙连接蛋白43的表达及生胃酮的保护作用[J]. 中风与神经疾病杂志, 2008, 25(5): 540-543.
14. 　Rouach N, Koulakoff A, Abudara V, et al. Astroglial metabolic networks sustain hippocampal synaptic transmission[J]. Science, 2008, 322(5907), 1551-1555.
15. 　Seifert g, Carmignoto G, Steinhuser C. Astrocyte dysfunction in epilepsy[J]. Brain Res Rev, 2010, 63(1-2): 212-221.
16. 　Benarroch EE. Astrocyte-neuron interactions implications for epilepsy[J]. Neurology, 2009, 73(16): 1323-1327.
17. 　Friedman A, Kaufer D, Heinemann U. Blood-brain barrier breakdown-inducing astrocytic transformation: novel targets for the prevention of epilepsy[J]. Epilepsy Res, 2009, 85(2-3): 142-149.
18. 　Djukic B, Casper KB, Philpot BD, et al. Conditional knock-out of Kir4. 1 leads to glial membrane depolarization, inhibition of potassium and glutamate uptake, and enhanced short-term synaptic potentiation[J]. J Neurosci, 2007, 27(42): 11354-11365.
19. 　Seifert G, Schilling K, Steinhuser C. Astrocyte dysfunction in neurological disorders: a molecular perspective[J]. Nat Rev Neurosci, 2006, 7(3): 194-206.
20. 　Eid T, Ghosh A, Wang Y, et al. Recurrent seizures and brain pathology after inhibition of glutamine synthetase in the hippocampus in rats[J]. Brain, 2008, 131(pt8), 2061-2070.
21. 　Eid T, Thomas MJ, Spencer DD, et al. Loss of glutamine synthetase in the human epileptogenic hippocampus: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy[J]. Lancet, 2004, 363(9402): 28-37.
22. 　卫向红, 李正莉, 朱长庚, 等. 激活的星形胶质细胞条件培养液致痫效应及其对大鼠脑内Glu和IL-2 R表达的影响[J]. 中国组织化学与细胞化学杂志, 2007, 16(4): 446-450.
23. 　Boison D. Adenosine augmentation therapies (AATs) for epilepsy: Prospect of cell and gene therapies[J]. Epilepsy Res, 2009, 85(2-3): 131-141.
24. 　Fedele DE, Gouder N, Guttinger M, et al. Astrogliosis in epilepsy leads to over expression of adenosine kinase, resulting in seizure aggravation[J]. Brain, 2005, 128(10): 2383-2395.
25. 　Haspolat S, Mihci E, Coskun M, et al. Interleukin-1β, tumor necrosis factor-a, and nitrite levels in febrile seizures[J]. Child Neurol, 2002, 17(10): 749-751.
26. 　Ravizza T, Noé F, Zardoni D, et al. Interleukin Converting Enzyme inhibition impairs kindling epileptogenesis in rats by blocking astrocytic IL-1beta production[J]. Neurobiol Dis, 2008, 31(3): 327-333.
27. 　Tian GF, Azmi H, Takano T, et al. An astrocytic basis of epilepsy[J]. Nat Med, 2005, 11(9): 973-981.
28. 　Plata-Salaman CR, Ilyin SE, Turrin NP, et al. Kindling modulates the IL-1beta system, TNF-alpha, TGF-beta1, and neuropeptide mRNAs in specific brain regions[J]. Brain Res Mol Brain Res, 2000, 75(2): 248-258.
29. 　Morganti-Kossmann MC, Rancan M, Stahel PF, et al. Inflammatory response in acute traumatic brain injury: a double-edged sword[J]. Curr Opin Crit Care, 2002, 8(2): 101-105.
30. 　Perillan PR, Chen M, Potts EA, et al. Transforming growth factor-beta 1 regulates Kir2. 3 inward rectifier K+ channels via phospholipase C and protein kinase C-delta in reactive astrocytes from adult rat brain[J]. J Biol Chem, 2002, 277(3): 1974-1980.
31. 　Ding G, Jiang Q, Li L, et al. Detection of BBB disruption and hemorrhage by Gd-DTPA enhanced MRI after embolic stroke in rat[J]. Brain Res, 2006, 1114(1): 195-203.

West China Medical Journal

血脑屏障破坏参与癫痫发生机制的研究进展

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