高迁移率族蛋白1在缺血性卒中急性期和癫痫急性发作中的研究进展_Journal of Epilepsy

Authors：

陶敏 ,  马勋泰

成都医学院第一附属医院神经内科（成都 610500）;

Corresponding author：

马勋泰, Email: maxuntai2002@126.com

Keywords：

HMGB1; 缺血性卒中; 癫痫; 缺血性卒中后癫痫

DOI：

10.7507/2096-0247.202204017

Video：

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Abstract Full text Figures/Tables Video References Cited by

高迁移率族蛋白1（High mobility group protein box 1， HMGB1）是在哺乳动物体内广泛表达的一种非组蛋白染色体结合蛋白，在细胞外与糖基化终末产物受体（Glycosylation receptor，RAGE）、Toll 样受体4（Toll-like receptors 4，TLR4）等相互作用，促进炎性因子分泌、神经元细胞生长发育及肿瘤细胞生长迁移等。HMGB1 在多种神经元疾病中均有影响，尤其在急性缺血性卒中及癫痫疾病过程中起重要作用，通过易位和释放，结合下游受体、促进细胞兴奋性、损坏血脑屏障等方式促进缺血性脑卒中及癫痫的发生发展，而目前尚未发现HMGB1在缺血性卒中后癫痫中所发挥的作用，因此该篇综述通过总结归纳 HMGB1 在缺血性脑卒中和癫痫之间的研究机制，为其在缺血性卒中后癫痫发生机制的相关性等提供新的研究思路。

Citation： 陶敏, 马勋泰. 高迁移率族蛋白1在缺血性卒中急性期和癫痫急性发作中的研究进展. Journal of Epilepsy, 2022, 8(5): 442-447. doi: 10.7507/2096-0247.202204017 Copy

1.	Lühdorf K, Jensen LK, Plesner AM. Etiology of seizures in the elderly. Epilepsia, 1986, 27(4): 458-463.
2.	Seshadri S, Wolf PA. Lifetime risk of stroke and dementia: current concepts, and estimates from the Framingham Study. Lancet Neurol, 2007, 6(12): 1106-1014.
3.	Beghi E, Carpio A, Forsgren L, et al. Recommendation for a definition of acute symptomatic seizure. Epilepsia, 2010, 51(4): 671-675.
4.	Hesdorffer DC, Benn EK, Cascino GD, et al. Is a first acute symptomatic seizure epilepsy? Mortality and risk for recurrent seizure. Epilepsia, 2009, 50(5): 1102-1108.
5.	Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia, 2014, 55(4): 475-482.
6.	Ferlazzo E, Gasparini S, Beghi E, et al. Epilepsy in cerebrovascular diseases: review of experimental and clinical data with meta-analysis of risk factors. Epilepsia, 2016, 57(8): 1205-1214.
7.	Ma A, Al A, Ea A, et al. Incidence, predictors, and outcome of early seizures after mechanical thrombectomy. Journal of the Neurological Sciences, 2019, 396: 235-239.
8.	Galanopoulou AS, Löscher W, Lubbers L, et al. Antiepileptogenesis and disease modification: progress, challenges, and the path forward-Report of the Preclinical Working Group of the 2018 NINDS-sponsored antiepileptogenesis and disease modification workshop. Epilepsia Open, 2021, 6(2): 276-296.
9.	Stros M. HMGB proteins: interactions with DNA and chromatin. Biochim Biophys Acta, 2010, 1799(1-2): 101-113.
10.	Ulloa L, Messmer D. High-mobility group box 1 (HMGB1) protein: friend and foe. Cytokine Growth Factor Rev, 2006, 17(3): 189-201.
11.	Harris HE, Andersson U, Pisetsky DS. HMGB1: a multifunctional alarmin driving autoimmune and inflammatory disease. Nat Rev Rheumatol, 2012, 8(4): 195-202.
12.	Naglova H, Bucova M. HMGB1 and its physiological and pathological roles. Bratisl Lek Listy, 2012, 113(3): 163-171.
13.	Venereau E, De Leo F, Mezzapelle R, et al. HMGB1 as biomarker and drug target. Pharmacol Res, 2016, 111: 534-544.
14.	Maroso M, Balosso S, Ravizza T, et al. Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures. Nat. Med, 2010, 16(4): 413-419.
15.	Kim JB, Choi JS, Yu YM, et al. HMGB1, a novel cytokine-like mediator linking acute neuronal death and delayed neuroinflammation in the postischemic brain. J Neurosci, 2006, 26(24): 6413-6421.
16.	Wang J, Hu X, Xie J, et al. Beta-1-adrenergic receptors mediate Nrf2-HO-1-HMGB1 axis regulation to attenuate hypoxia/reoxygenation-induced cardiomyocytes injury in vitro. Cell Physiol Biochem, 2015, 35(2): 767-777.
17.	Fujita K, Motoki K, Tagawa K, et al. HMGB1, a pathogenic molecule that induces neurite degeneration via TLR4-MARCKS, is a potential therapeutic target for Alzheimer’s disease. Sci Rep, 2016, 6: 31895.
18.	Okuma Y, Liu K, Wake H, et al. Anti–high mobility group box-1 antibody therapy for traumatic brain injury. Yakugaku Zasshi, 2014, 134(6): 701-705.
19.	Sasaki T, Liu K, Agari T, et al. Anti-high mobility group box 1 antibody exerts neuroprotection in a rat model of Parkinson’s disease. Exp Neurol, 2016, 275(Pt 1): 220-231.
20.	Andersson Å, Covacu R, Sunnemark D, et al. Pivotal advance:HMGB1 expression in active lesions of human and experimental multiple sclerosis. Leukoc. Biol, 2008, 84: 1248-1255.
21.	Andersson U, Yang H, Harris, H. Extracellular HMGB1 as a therapeutic target in inflammatory diseases. Expert Opin Ther Targets, 2018, 22(3): 263-277.
22.	Bianchi ME, Crippa MP, Manfredi AA, et al. High-mobility group box 1 protein orchestrates responses to tissue damage via inflammation, innate and adaptive immunity and tissue repair. Immunol. Immunol Rev, 2017, 280(1): 74-82.
23.	Kim JB, Lim CM, Yu YM, et al. Induction and subcellular localization of high-mobility group box-1 (HMGB1) in the postischemic rat brain. J Neurosci Res, 2008, 86(5): 1125-1131.
24.	Liesz A, Dalpke A, Mracsko E, et al. DAMP signaling is a key pathway inducing immune modulation after brain injury. J Neurosci, 2015, 35(2): 583-598.
25.	Zhang J, Wu Y, Weng Z, et al. Glycyrrhizin protects brain against ischemia-reperfusion injury in mice through HMGB1-TLR4-IL-17A signaling pathway. Brain Res, 2014, 1582: 176-186.
26.	Zhang J, Takahashi HK, Liu K, et al. Anti-high mobility group box-1 monoclonal antibody protects the blood-brain barrier from ischemia-induced disruption in rats. Stroke, 2011, 42(5): 1420-1428.
27.	Wang J, Han D, Sun M, et al. A combination of remote ischemic perconditioning and cerebral ischemic postconditioning inhibits autophagy to attenuate plasma HMGB1 and induce neuroprotection against stroke in rat. J Mol Neurosci, 2016, 58(4): 424-431.
28.	Dai S, Zheng Y, WangY, et al. HMGB1, neuronal excitability and epilepsy. Acta Epileptologica, 2021, 3(1): 9.
29.	Iori V, Maroso M, Rizzi M, et al. Receptor for advanced glycation Endproducts is upregulated in temporal lobe epilepsy and contributes to experimental seizures. Neurobiol Dis, 2013, 58: 102-114.
30.	Zurolo E, Iyer A, Maroso M, et al. Activation of toll-like receptor, RAGE and HMGB1 signalling in malformations of cortical development. Brain, 2011, 134(Pt 4): 1015-1032.
31.	Zhang Z, Liu Q, Liu M, et al. Upregulation of HMGB1-TLR4 inflammatory pathway in focal cortical dysplasia type II. J Neuroinflammation, 2018, 15(1): 27.
32.	Han Y, Yang L, Liu X, et al. HMGB1/CXCL12-mediated immunity and Th17 cells might underlie highly suspected autoimmune epilepsy in elderly individuals. Neuropsychiatr Dis Treat, 2020, 16: 1285-1293.
33.	Ai P, Zhang X, Xie Z, et al. The HMGB1 is increased in CSF of patients with an anti-NMDAR encephalitis. Acta Neurol Scand, 2018, 137(2): 277-282.
34.	Lauren W, Karen T, Emanuele R, et al. High mobility group box 1 in the inflammatory pathogenesis of epilepsy: profiling circulating levels after experimental and clinical seizures. Lancet, 2014, 383(Suppl 1): S105-S105.
35.	Kan M, ong L, Zhang X, et al. Circulating high mobility group box-1 and toll-like receptor 4 expressions increase the risk and severity of epilepsy. Braz J Med Biol Res, 2019, 52(7): 230-235.
36.	Liu AH, Wu YT, Wang YP. MicroRNA-129-5p inhibits the development of autoimmune encephalomyelitis-related epilepsy by targeting HMGB1 through the TLR4/NF-kB signaling pathway. Brain Res Bull, 2017, 132: 139-149.
37.	Ravizza T, Terrone G, Salamone A, et al. High mobility group box 1 is a novel pathogenic factor and a mechanistic biomarker for epilepsy. Brain Behav Immun, 2018, 72: 14-21.
38.	Balosso S, Liu J, Bianchi ME, et al. Disulfide-containing high mobility group box-1 promotes N-methyl-D-aspartate receptor function and excitotoxicity by activating toll-like receptor 4-dependent signaling in hippocampal neurons. Antioxid Redox Signal, 2014, 21(12): 1726-1740.
39.	Iori V, Iyer AM, Ravizza T, et al. Blockade of the IL-1R1/TLR4 pathway mediates disease-modification therapeutic effects in a model of acquired epilepsy. Neurobiol Dis, 2017, 99: 12-23.
40.	De Simoni MG, Perego C, Ravizza T, etl. Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus. Eur J Neurosci, 2000, 12(7): 2623-2633.
41.	Boer K, Spliet WG, van Rijen PC, et al. Evidence of activated microglia in focal cortical dysplasia. J Neuroimmunol, 2006, 173(1-2): 188-195.
42.	Ravizza T, Boer K, Redeker S, et al. The IL-1beta system in epilepsy-associated malformations of cortical development. Neurobiol Dis, 2006, 24(1): 128-143.
43.	Zhao J, Zheng Y, Liu K, et al. HMGB1 is a therapeutic target and biomarker in diazepam-refractory status epilepticus with wide time window. Neurotherapeutics, 2020, 17(2): 710-721.
44.	Luo L, Jin Y, Kim ID, et al. Glycyrrhizin attenuates kainic acid-induced neuronal cell death in the mouse hippocampus. Exp Neurobiol, 2013, 22(2): 107-115.
45.	Doria JW, Forgacs PB. Incidence, Implications, and Management of Seizures Following Ischemic and Hemorrhagic Stroke. Curr Neurol Neurosci Rep, 2019, 19(7): 37.
46.	Bladin CF, Alexandrov AV, Bellavance A, et al. Seizures after stroke: a prospective multicenter study. Arch Neurol, 2000, 57(11): 1617-1622.
47.	Lambrakis CC, Lancman ME. The phenomenology of seizures and epilepsy after stroke. Epilepsy, 1998, 11: 233-40.
48.	Feyissa AM, Hasan TF, Meschia JF. Stroke-related epilepsy. European Journal of Neurology, 2019, 26(1): 18-23.
49.	Kamp MA, Dibue M, Schneider T, et al. Calcium and potassium channels in experimental subarachnoid hemorrhage and transient global ischemiav. Stroke Res Treat, 2012, 2012: 382146.
50.	Feher G, Gurdan Z, Gombos K, et al. Early seizures after ischemic stroke: focus on thrombolysis. CNS Spectr, 2020, 25(1): 101-113.
51.	Kim SY, Buckwalter M, Soreq H, et al. Blood-brain barrier dysfunction-induced inflammatory signaling in brain pathology and epileptogenesis. Epilepsia, 2012, 53(Suppl 6): 37-44.
52.	Tanaka T, Ihara M. Post-stroke epilepsy. Neurochem Int, 2017, 107: 219-228.
53.	Xie WJ, Dong M, Liu Q, et al. Early predictors and prevention for post-stroke epilepsy: changes in neurotransmitter levels. Translational Neuroscience, 2016, 7(1): 1-5.
54.	Sun DA, Sombati S, DeLorenzo R. Glutamate injury-induced epileptogenesis in hippocampal neurons: an in vitro model of stroke-induced “epilepsy”. Stroke, 2001, 32(10): 2344-2350.
55.	Klein P, Dingledine R, Aronica E, et al. Commonalities in epileptogenic processes from different acute brain insults: do they translate. Epilepsia, 2018, 59(1): 37-66.
56.	Zhou H, Wang N, Xu L, et al. The efficacy of gastrodin in combination with folate and vitamin B12 on patients with epilepsy after stroke and its effect on HMGB-1, IL-2 and IL-6 serum levels. Exp Ther Med, 2017, 14(5): 4801-4806.
57.	Tao S, Sun J, Hao F, et al. Effects of sodium valproate combined with lamotrigine on quality of life and serum inflammatory factors in patients with poststroke secondary epilepsy. Stroke Cerebrovasc Dis, 2020, 29(5): 104644.

1. Lühdorf K, Jensen LK, Plesner AM. Etiology of seizures in the elderly. Epilepsia, 1986, 27(4): 458-463.
2. Seshadri S, Wolf PA. Lifetime risk of stroke and dementia: current concepts, and estimates from the Framingham Study. Lancet Neurol, 2007, 6(12): 1106-1014.
3. Beghi E, Carpio A, Forsgren L, et al. Recommendation for a definition of acute symptomatic seizure. Epilepsia, 2010, 51(4): 671-675.
4. Hesdorffer DC, Benn EK, Cascino GD, et al. Is a first acute symptomatic seizure epilepsy? Mortality and risk for recurrent seizure. Epilepsia, 2009, 50(5): 1102-1108.
5. Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia, 2014, 55(4): 475-482.
6. Ferlazzo E, Gasparini S, Beghi E, et al. Epilepsy in cerebrovascular diseases: review of experimental and clinical data with meta-analysis of risk factors. Epilepsia, 2016, 57(8): 1205-1214.
7. Ma A, Al A, Ea A, et al. Incidence, predictors, and outcome of early seizures after mechanical thrombectomy. Journal of the Neurological Sciences, 2019, 396: 235-239.
8. Galanopoulou AS, Löscher W, Lubbers L, et al. Antiepileptogenesis and disease modification: progress, challenges, and the path forward-Report of the Preclinical Working Group of the 2018 NINDS-sponsored antiepileptogenesis and disease modification workshop. Epilepsia Open, 2021, 6(2): 276-296.
9. Stros M. HMGB proteins: interactions with DNA and chromatin. Biochim Biophys Acta, 2010, 1799(1-2): 101-113.
10. Ulloa L, Messmer D. High-mobility group box 1 (HMGB1) protein: friend and foe. Cytokine Growth Factor Rev, 2006, 17(3): 189-201.
11. Harris HE, Andersson U, Pisetsky DS. HMGB1: a multifunctional alarmin driving autoimmune and inflammatory disease. Nat Rev Rheumatol, 2012, 8(4): 195-202.
12. Naglova H, Bucova M. HMGB1 and its physiological and pathological roles. Bratisl Lek Listy, 2012, 113(3): 163-171.
13. Venereau E, De Leo F, Mezzapelle R, et al. HMGB1 as biomarker and drug target. Pharmacol Res, 2016, 111: 534-544.
14. Maroso M, Balosso S, Ravizza T, et al. Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures. Nat. Med, 2010, 16(4): 413-419.
15. Kim JB, Choi JS, Yu YM, et al. HMGB1, a novel cytokine-like mediator linking acute neuronal death and delayed neuroinflammation in the postischemic brain. J Neurosci, 2006, 26(24): 6413-6421.
16. Wang J, Hu X, Xie J, et al. Beta-1-adrenergic receptors mediate Nrf2-HO-1-HMGB1 axis regulation to attenuate hypoxia/reoxygenation-induced cardiomyocytes injury in vitro. Cell Physiol Biochem, 2015, 35(2): 767-777.
17. Fujita K, Motoki K, Tagawa K, et al. HMGB1, a pathogenic molecule that induces neurite degeneration via TLR4-MARCKS, is a potential therapeutic target for Alzheimer’s disease. Sci Rep, 2016, 6: 31895.
18. Okuma Y, Liu K, Wake H, et al. Anti–high mobility group box-1 antibody therapy for traumatic brain injury. Yakugaku Zasshi, 2014, 134(6): 701-705.
19. Sasaki T, Liu K, Agari T, et al. Anti-high mobility group box 1 antibody exerts neuroprotection in a rat model of Parkinson’s disease. Exp Neurol, 2016, 275(Pt 1): 220-231.
20. Andersson Å, Covacu R, Sunnemark D, et al. Pivotal advance:HMGB1 expression in active lesions of human and experimental multiple sclerosis. Leukoc. Biol, 2008, 84: 1248-1255.
21. Andersson U, Yang H, Harris, H. Extracellular HMGB1 as a therapeutic target in inflammatory diseases. Expert Opin Ther Targets, 2018, 22(3): 263-277.
22. Bianchi ME, Crippa MP, Manfredi AA, et al. High-mobility group box 1 protein orchestrates responses to tissue damage via inflammation, innate and adaptive immunity and tissue repair. Immunol. Immunol Rev, 2017, 280(1): 74-82.
23. Kim JB, Lim CM, Yu YM, et al. Induction and subcellular localization of high-mobility group box-1 (HMGB1) in the postischemic rat brain. J Neurosci Res, 2008, 86(5): 1125-1131.
24. Liesz A, Dalpke A, Mracsko E, et al. DAMP signaling is a key pathway inducing immune modulation after brain injury. J Neurosci, 2015, 35(2): 583-598.
25. Zhang J, Wu Y, Weng Z, et al. Glycyrrhizin protects brain against ischemia-reperfusion injury in mice through HMGB1-TLR4-IL-17A signaling pathway. Brain Res, 2014, 1582: 176-186.
26. Zhang J, Takahashi HK, Liu K, et al. Anti-high mobility group box-1 monoclonal antibody protects the blood-brain barrier from ischemia-induced disruption in rats. Stroke, 2011, 42(5): 1420-1428.
27. Wang J, Han D, Sun M, et al. A combination of remote ischemic perconditioning and cerebral ischemic postconditioning inhibits autophagy to attenuate plasma HMGB1 and induce neuroprotection against stroke in rat. J Mol Neurosci, 2016, 58(4): 424-431.
28. Dai S, Zheng Y, WangY, et al. HMGB1, neuronal excitability and epilepsy. Acta Epileptologica, 2021, 3(1): 9.
29. Iori V, Maroso M, Rizzi M, et al. Receptor for advanced glycation Endproducts is upregulated in temporal lobe epilepsy and contributes to experimental seizures. Neurobiol Dis, 2013, 58: 102-114.
30. Zurolo E, Iyer A, Maroso M, et al. Activation of toll-like receptor, RAGE and HMGB1 signalling in malformations of cortical development. Brain, 2011, 134(Pt 4): 1015-1032.
31. Zhang Z, Liu Q, Liu M, et al. Upregulation of HMGB1-TLR4 inflammatory pathway in focal cortical dysplasia type II. J Neuroinflammation, 2018, 15(1): 27.
32. Han Y, Yang L, Liu X, et al. HMGB1/CXCL12-mediated immunity and Th17 cells might underlie highly suspected autoimmune epilepsy in elderly individuals. Neuropsychiatr Dis Treat, 2020, 16: 1285-1293.
33. Ai P, Zhang X, Xie Z, et al. The HMGB1 is increased in CSF of patients with an anti-NMDAR encephalitis. Acta Neurol Scand, 2018, 137(2): 277-282.
34. Lauren W, Karen T, Emanuele R, et al. High mobility group box 1 in the inflammatory pathogenesis of epilepsy: profiling circulating levels after experimental and clinical seizures. Lancet, 2014, 383(Suppl 1): S105-S105.
35. Kan M, ong L, Zhang X, et al. Circulating high mobility group box-1 and toll-like receptor 4 expressions increase the risk and severity of epilepsy. Braz J Med Biol Res, 2019, 52(7): 230-235.
36. Liu AH, Wu YT, Wang YP. MicroRNA-129-5p inhibits the development of autoimmune encephalomyelitis-related epilepsy by targeting HMGB1 through the TLR4/NF-kB signaling pathway. Brain Res Bull, 2017, 132: 139-149.
37. Ravizza T, Terrone G, Salamone A, et al. High mobility group box 1 is a novel pathogenic factor and a mechanistic biomarker for epilepsy. Brain Behav Immun, 2018, 72: 14-21.
38. Balosso S, Liu J, Bianchi ME, et al. Disulfide-containing high mobility group box-1 promotes N-methyl-D-aspartate receptor function and excitotoxicity by activating toll-like receptor 4-dependent signaling in hippocampal neurons. Antioxid Redox Signal, 2014, 21(12): 1726-1740.
39. Iori V, Iyer AM, Ravizza T, et al. Blockade of the IL-1R1/TLR4 pathway mediates disease-modification therapeutic effects in a model of acquired epilepsy. Neurobiol Dis, 2017, 99: 12-23.
40. De Simoni MG, Perego C, Ravizza T, etl. Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus. Eur J Neurosci, 2000, 12(7): 2623-2633.
41. Boer K, Spliet WG, van Rijen PC, et al. Evidence of activated microglia in focal cortical dysplasia. J Neuroimmunol, 2006, 173(1-2): 188-195.
42. Ravizza T, Boer K, Redeker S, et al. The IL-1beta system in epilepsy-associated malformations of cortical development. Neurobiol Dis, 2006, 24(1): 128-143.
43. Zhao J, Zheng Y, Liu K, et al. HMGB1 is a therapeutic target and biomarker in diazepam-refractory status epilepticus with wide time window. Neurotherapeutics, 2020, 17(2): 710-721.
44. Luo L, Jin Y, Kim ID, et al. Glycyrrhizin attenuates kainic acid-induced neuronal cell death in the mouse hippocampus. Exp Neurobiol, 2013, 22(2): 107-115.
45. Doria JW, Forgacs PB. Incidence, Implications, and Management of Seizures Following Ischemic and Hemorrhagic Stroke. Curr Neurol Neurosci Rep, 2019, 19(7): 37.
46. Bladin CF, Alexandrov AV, Bellavance A, et al. Seizures after stroke: a prospective multicenter study. Arch Neurol, 2000, 57(11): 1617-1622.
47. Lambrakis CC, Lancman ME. The phenomenology of seizures and epilepsy after stroke. Epilepsy, 1998, 11: 233-40.
48. Feyissa AM, Hasan TF, Meschia JF. Stroke-related epilepsy. European Journal of Neurology, 2019, 26(1): 18-23.
49. Kamp MA, Dibue M, Schneider T, et al. Calcium and potassium channels in experimental subarachnoid hemorrhage and transient global ischemiav. Stroke Res Treat, 2012, 2012: 382146.
50. Feher G, Gurdan Z, Gombos K, et al. Early seizures after ischemic stroke: focus on thrombolysis. CNS Spectr, 2020, 25(1): 101-113.
51. Kim SY, Buckwalter M, Soreq H, et al. Blood-brain barrier dysfunction-induced inflammatory signaling in brain pathology and epileptogenesis. Epilepsia, 2012, 53(Suppl 6): 37-44.
52. Tanaka T, Ihara M. Post-stroke epilepsy. Neurochem Int, 2017, 107: 219-228.
53. Xie WJ, Dong M, Liu Q, et al. Early predictors and prevention for post-stroke epilepsy: changes in neurotransmitter levels. Translational Neuroscience, 2016, 7(1): 1-5.
54. Sun DA, Sombati S, DeLorenzo R. Glutamate injury-induced epileptogenesis in hippocampal neurons: an in vitro model of stroke-induced “epilepsy”. Stroke, 2001, 32(10): 2344-2350.
55. Klein P, Dingledine R, Aronica E, et al. Commonalities in epileptogenic processes from different acute brain insults: do they translate. Epilepsia, 2018, 59(1): 37-66.
56. Zhou H, Wang N, Xu L, et al. The efficacy of gastrodin in combination with folate and vitamin B12 on patients with epilepsy after stroke and its effect on HMGB-1, IL-2 and IL-6 serum levels. Exp Ther Med, 2017, 14(5): 4801-4806.
57. Tao S, Sun J, Hao F, et al. Effects of sodium valproate combined with lamotrigine on quality of life and serum inflammatory factors in patients with poststroke secondary epilepsy. Stroke Cerebrovasc Dis, 2020, 29(5): 104644.

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高迁移率族蛋白1在缺血性卒中急性期和癫痫急性发作中的研究进展

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