Research progress on the mechanism and therapeutic targets of brain injury caused by status epilepticus_Journal of Epilepsy

Authors：

JIANG Yingnan ¹ , GUO Jia ¹ , KONG Qingxia ² ,  HUANG Shuran ³

1. Clinical Medical College of Jining Medical University, Jining 272000, China;
2. Department of Neurology, Affiliated Hospital of Jining Medical University, Jining 272000, China;
3. Department of Critical Care Medicine, Affiliated Hospital of Jining Medical University, Jining 272000, China;

Corresponding?author：

HUANG Shuran, Email: isabeir@163.com

Keywords：

Status epilepticus; Brain damage; Therapeutic target; Neuroinflammation; Cell autophagy

DOI：

10.7507/2096-0247.202310012

Video：

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Epilepsy is one of the most common neurological disorders, and status epilepticus (SE) can lead to permanent neuronal brain damage in the central nervous system, but the mechanism is not clear. Solving this problem will help to find more SE therapeutic targets, benefiting tens of millions of epilepsy patients. The pathway of SE leading to neuronal damage in the brain has made new progress in neuroinflammation, autophagy, apoptosis and pyroptosis, glial cell hyperplasia and category transformation, and changes in neurotransmitters in the brain, which will be beneficial to the discovery of new targets for the treatment of SE, thus laying a foundation for the development of new anti-epileptic drugs.

Citation： JIANG Yingnan, GUO Jia, KONG Qingxia, HUANG Shuran. Research progress on the mechanism and therapeutic targets of brain injury caused by status epilepticus. Journal of Epilepsy, 2024, 10(1): 83-87. doi: 10.7507/2096-0247.202310012 Copy

1.	Betjemann JP, Lowenstein DH. Status epilepticus in adults. Lancet Neurol, 2015, 14(6): 615-24.
2.	Pinto LF, Oliveira JPS, Midon AM. Status epilepticus: review on diagnosis, monitoring and treatment. Arq Neuropsiquiatr, 2022, 80(5 Suppl 1): 193-203.
3.	Terrone G, Frigerio F, Balosso S, et al. Inflammation and reactive oxygen species in status epilepticus: Biomarkers and implications for therapy. Epilepsy Behav , 2019, 101(Pt B): 106275.
4.	Li TR, Jia YJ, Wang Q, et al. Correlation between tumor necrosis factor alpha mRNA and microRNA-155 expression in rat models and patients with temporal lobe epilepsy. Brain Res, 2018, 1700: 56-65.
5.	Cai Z, Li S, Li S, et al. Antagonist targeting microRNA-155 protects against lithium-pilocarpine-induced status epilepticus in C57BL/6 mice by activating brain-derived neurotrophic factor. Front Pharmacol, 2016, 7: 129.
6.	Costagliola G, Depietri G, Michev A, et al. Targeting inflammatory mediators in epilepsy: a systematic review of its molecular basis and clinical applications. Front Neurol, 2022, 13: 741244.
7.	Yang QW, Wang JZ, Li JC, et al. High-mobility group protein box-1 and its relevance to cerebral ischemia. J Cereb Blood Flow Metab, 2010, 30(2): 243-254.
8.	Li YJ, Wang L, Zhang B, et al. Glycyrrhizin, an HMGB1 inhibitor, exhibits neuroprotective effects in rats after lithium-pilocarpine-induced status epilepticus. J Pharm Pharmacol, 2019, 71(3): 390-399.
9.	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.
10.	歐詒丹, 陳靜, 高元杰. 注射用神經節苷脂鈉對癲癇持續狀態大鼠認知功能障礙及神經炎癥的改善作用及機制. 廣西醫學, 2021, 43(23): 2838-2844.
11.	馮文之, 陳揚, 俞立. 細胞自噬分子機制的進展. 生命科學, 2015, 27(7): 859-866.
12.	崔瑩. HMGB1在癲癇小鼠海馬損傷中的作用及機制研究. 山東大學, 博士學位論文, 2020.
13.	高曉宇. 天麻素對小鼠癲癇持續狀態后海馬組織自噬的作用及機制. 延安大學, 碩士學位論文, 2020.
14.	楊濱. 黃芩苷通過PI3K/Akt/mTOR通路上調癲癇大鼠海馬自噬活性及其神經保護作用的研究. 福建醫科大學, 碩士學位論文, 2019.
15.	鄭雪姣. PDCD4/自噬信號通路及凋亡在大鼠癲癇持續狀態中的變化. 延安大學, 碩士學位論文, 2020.
16.	郝佳朵. PDCD4經自噬信號通路在小鼠癲癇持續狀態中的作用及其機制研究. 延安大學, 碩士學位論文, 2022.
17.	Yue J, He J, Wei Y, et al. Decreased expression of Rev-Erbα in the epileptic foci of temporal lobe epilepsy and activation of Rev-Erbα have anti-inflammatory and neuroprotective effects in the pilocarpine model. J Neuroinflammation, 2020, 17(1): 43.
18.	Sheng M, Chen X, Yu Y, et al. Rev-erbα agonist SR9009 protects against cerebral ischemic injury through mechanisms involving Nrf2 pathway. Front Pharmacol, 2023, 14: 1102567.
19.	于江華, 史志勤, 蘇旭東, 等. 重組人促紅細胞生成素對大鼠癲癇持續狀態X-連鎖凋亡抑制蛋白的影響及作用機制的實驗研究. 腦與神經疾病雜志, 2018, 26(6): 357-362.
20.	Xia L, Liu L, Wang Q, et al. Relationship between the pyroptosis pathway and epilepsy: a bioinformatic analysis. Front Neurol, 2021, 12: 782739.
21.	Deshpande T, Li T, Henning L, et al. Constitutive deletion of astrocytic connexins aggravates kainate-induced epilepsy, Glia 2020, 68(10): 2136-2147.
22.	于濤. miRNA-106b-5p對癲癇持續狀態小鼠海馬小膠質細胞激活極化的影響及機制研究. 中國醫科大學, 博士學位論文, 2022.
23.	袁振宇. 長效GLP-1受體激動劑索馬魯肽對大鼠癲癇持續狀態后海馬小膠質細胞表型轉化和神經炎癥的影響及機制研究. 山西醫科大學, 碩士學位論文, 2020.
24.	Wen Y, Wu K, Xie Y, et al. Inhibitory effects of glucagon-like peptide-1 receptor on epilepsy. Biochem Biophys Res Commun, 2019, 511(1): 79-86.
25.	Gan J, Huang L, Qu Y, et al. Expression and functional analysis of lncRNAs in the hippocampus of immature rats with status epilepticus. J Cell Mol Med, 2020, 24(1): 149-159.
26.	Hu F, Shao L, Zhang J, et al. Knockdown of ZFAS1 inhibits hippocampal neurons apoptosis and autophagy by activating the PI3K/AKT pathway via up-regulating miR-421 in epilepsy. Neurochem Res, 2020, 45(10): 2433-2441.
27.	Diespirov GP, Postnikova TY, Griflyuk AV, et al. Alterations in the properties of the rat hippocampus glutamatergic system in the lithium-pilocarpine model of temporal lobe epilepsy. Biochemistry (Mosc), 2023, 88(3): 353-363.
28.	Gorlewicz A, Pijet B, Orlova K, et al. Epileptiform GluN2B-driven excitation in hippocampus as a therapeutic target against temporal lobe epilepsy. Exp Neurol, 2022, 354: 114087.
29.	Deng N, Hu J, Hong Y, et al. Indoleamine-2, 3-Dioxygenase 1 deficiency suppresses seizures in epilepsy. Front Cell Neurosci, 2021, 15: 638854.
30.	吳紀添, 張永全, 胡芷穎, 等. 天麻對癲癇的影響及潛在機制. 中國醫學創新, 2023, 20(2): 184-188.

1. Betjemann JP, Lowenstein DH. Status epilepticus in adults. Lancet Neurol, 2015, 14(6): 615-24.
2. Pinto LF, Oliveira JPS, Midon AM. Status epilepticus: review on diagnosis, monitoring and treatment. Arq Neuropsiquiatr, 2022, 80(5 Suppl 1): 193-203.
3. Terrone G, Frigerio F, Balosso S, et al. Inflammation and reactive oxygen species in status epilepticus: Biomarkers and implications for therapy. Epilepsy Behav , 2019, 101(Pt B): 106275.
4. Li TR, Jia YJ, Wang Q, et al. Correlation between tumor necrosis factor alpha mRNA and microRNA-155 expression in rat models and patients with temporal lobe epilepsy. Brain Res, 2018, 1700: 56-65.
5. Cai Z, Li S, Li S, et al. Antagonist targeting microRNA-155 protects against lithium-pilocarpine-induced status epilepticus in C57BL/6 mice by activating brain-derived neurotrophic factor. Front Pharmacol, 2016, 7: 129.
6. Costagliola G, Depietri G, Michev A, et al. Targeting inflammatory mediators in epilepsy: a systematic review of its molecular basis and clinical applications. Front Neurol, 2022, 13: 741244.
7. Yang QW, Wang JZ, Li JC, et al. High-mobility group protein box-1 and its relevance to cerebral ischemia. J Cereb Blood Flow Metab, 2010, 30(2): 243-254.
8. Li YJ, Wang L, Zhang B, et al. Glycyrrhizin, an HMGB1 inhibitor, exhibits neuroprotective effects in rats after lithium-pilocarpine-induced status epilepticus. J Pharm Pharmacol, 2019, 71(3): 390-399.
9. 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.
10. 歐詒丹, 陳靜, 高元杰. 注射用神經節苷脂鈉對癲癇持續狀態大鼠認知功能障礙及神經炎癥的改善作用及機制. 廣西醫學, 2021, 43(23): 2838-2844.
11. 馮文之, 陳揚, 俞立. 細胞自噬分子機制的進展. 生命科學, 2015, 27(7): 859-866.
12. 崔瑩. HMGB1在癲癇小鼠海馬損傷中的作用及機制研究. 山東大學, 博士學位論文, 2020.
13. 高曉宇. 天麻素對小鼠癲癇持續狀態后海馬組織自噬的作用及機制. 延安大學, 碩士學位論文, 2020.
14. 楊濱. 黃芩苷通過PI3K/Akt/mTOR通路上調癲癇大鼠海馬自噬活性及其神經保護作用的研究. 福建醫科大學, 碩士學位論文, 2019.
15. 鄭雪姣. PDCD4/自噬信號通路及凋亡在大鼠癲癇持續狀態中的變化. 延安大學, 碩士學位論文, 2020.
16. 郝佳朵. PDCD4經自噬信號通路在小鼠癲癇持續狀態中的作用及其機制研究. 延安大學, 碩士學位論文, 2022.
17. Yue J, He J, Wei Y, et al. Decreased expression of Rev-Erbα in the epileptic foci of temporal lobe epilepsy and activation of Rev-Erbα have anti-inflammatory and neuroprotective effects in the pilocarpine model. J Neuroinflammation, 2020, 17(1): 43.
18. Sheng M, Chen X, Yu Y, et al. Rev-erbα agonist SR9009 protects against cerebral ischemic injury through mechanisms involving Nrf2 pathway. Front Pharmacol, 2023, 14: 1102567.
19. 于江華, 史志勤, 蘇旭東, 等. 重組人促紅細胞生成素對大鼠癲癇持續狀態X-連鎖凋亡抑制蛋白的影響及作用機制的實驗研究. 腦與神經疾病雜志, 2018, 26(6): 357-362.
20. Xia L, Liu L, Wang Q, et al. Relationship between the pyroptosis pathway and epilepsy: a bioinformatic analysis. Front Neurol, 2021, 12: 782739.
21. Deshpande T, Li T, Henning L, et al. Constitutive deletion of astrocytic connexins aggravates kainate-induced epilepsy, Glia 2020, 68(10): 2136-2147.
22. 于濤. miRNA-106b-5p對癲癇持續狀態小鼠海馬小膠質細胞激活極化的影響及機制研究. 中國醫科大學, 博士學位論文, 2022.
23. 袁振宇. 長效GLP-1受體激動劑索馬魯肽對大鼠癲癇持續狀態后海馬小膠質細胞表型轉化和神經炎癥的影響及機制研究. 山西醫科大學, 碩士學位論文, 2020.
24. Wen Y, Wu K, Xie Y, et al. Inhibitory effects of glucagon-like peptide-1 receptor on epilepsy. Biochem Biophys Res Commun, 2019, 511(1): 79-86.
25. Gan J, Huang L, Qu Y, et al. Expression and functional analysis of lncRNAs in the hippocampus of immature rats with status epilepticus. J Cell Mol Med, 2020, 24(1): 149-159.
26. Hu F, Shao L, Zhang J, et al. Knockdown of ZFAS1 inhibits hippocampal neurons apoptosis and autophagy by activating the PI3K/AKT pathway via up-regulating miR-421 in epilepsy. Neurochem Res, 2020, 45(10): 2433-2441.
27. Diespirov GP, Postnikova TY, Griflyuk AV, et al. Alterations in the properties of the rat hippocampus glutamatergic system in the lithium-pilocarpine model of temporal lobe epilepsy. Biochemistry (Mosc), 2023, 88(3): 353-363.
28. Gorlewicz A, Pijet B, Orlova K, et al. Epileptiform GluN2B-driven excitation in hippocampus as a therapeutic target against temporal lobe epilepsy. Exp Neurol, 2022, 354: 114087.
29. Deng N, Hu J, Hong Y, et al. Indoleamine-2, 3-Dioxygenase 1 deficiency suppresses seizures in epilepsy. Front Cell Neurosci, 2021, 15: 638854.
30. 吳紀添, 張永全, 胡芷穎, 等. 天麻對癲癇的影響及潛在機制. 中國醫學創新, 2023, 20(2): 184-188.

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Journal of Epilepsy

Research progress on the mechanism and therapeutic targets of brain injury caused by status epilepticus

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