神经炎症在婴儿痉挛发病机制中的研究进展_Journal of Epilepsy

Authors：

奚晓隽 ^1,2 ,  汤继宏 ¹

1. ;
2. ;

Corresponding author：

汤继宏, Email: tjhzsh@126.com

Keywords：

婴儿痉挛; 神经炎症; 发病机制

DOI：

10.7507/2096-0247.20200024

Video：

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婴儿痉挛（Infantile spasms，IS）是一种独特的，并有年龄依赖性的婴儿早期癫痫性脑病。具有发病年龄早、发作形式特殊、进行性认知损害、脑电图呈高峰失律等特征。其病因复杂、多样，发病机制尚未明确，治疗方面仍存在困难，大多遗留智能缺陷等后遗症。癫痫的发生与神经组织微环境中增加的强烈而持续的炎症状态相关，受损神经元组织中炎症细胞和分子的激活、分解调节障碍是癫痫发展的关键因素，炎症可能起源于中枢神经系统，或通过血脑屏障的破坏从全身循环获得。同时癫痫也可能激活促炎通路，导致神经炎症的发生。本文对近年神经炎症通路在 IS 发病机制中的作用研究进行综述，通过总结遗传学进展揭示了许多参与 IS 发病机制的基因，包括直接或间接参与炎症的基因，同时得到临床和 IS 动物模型的研究支持。了解 IS 发生发展过程中炎症的神经生物学将有助于开发新的生物标志物，以便更好地筛选高危患者，为探索 IS 治疗新靶点提供方向。

Citation： 奚晓隽, 汤继宏. 神经炎症在婴儿痉挛发病机制中的研究进展. Journal of Epilepsy, 2020, 6(2): 137-140. doi: 10.7507/2096-0247.20200024 Copy

1.	Wilmshurst JM, Ibekwe RC, O'Callaghan FJK. Epileptic spasms - 175 years on: Trying to teach an old dog new tricks. Seizure, 2017, 44: 81-86.
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3.	Ahmed R, Rubinger L, Go C, et al. Utility of additional dedicated high-resolution 3T MRI in children with medically refractory focal epilepsy. Epilepsy Res, 2018, 143: 113-119.
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5.	Mohamed BP, Scott RC, Desai N, et al. Seizure outcome in infantile spasms--a retrospective study. Epilepsia, 2011, 52(4): 746-752.
6.	Graeber MB, Li W, Rodriguez ML. Role of microglia in CNS inflammation. FEBS Lett, 2011, 585(23): 3798-3805.
7.	Vezzani A, Aronica E, Mazarati A, et al. Epilepsy and brain inflammation. Exp Neurol, 2013, 244(11-21).
8.	Auvin S, Cilio MR, Vezzani A. Current understanding and neurobiology of epileptic encephalopathies. Neurobiol Dis, 2016, 92(Pt A): 72-89.
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11.	Galic MA, Riazi K, Heida JG, et al. Postnatal inflammation increases seizure susceptibility in adult rats. J Neurosci, 2008, 28(27): 6904-6913.
12.	Vezzani A, Maroso M, Balosso S, et al. IL-1 receptor/Toll-like receptor signaling in infection, inflammation, stress and neurodegeneration couples hyperexcitability and seizures. Brain Behav Immun, 2011, 25(7): 1281-1289.
13.	Devinsky O, Vezzani A, Najjar S, et al. Glia and epilepsy: excitability and inflammation. Trends Neurosci, 2013, 36(3): 174-184.
14.	Galanopoulou A S, Moshe S L. Neonatal and Infantile Epilepsy: Acquired and Genetic Models. Cold Spring Harb Perspect Med, 2015, 6(1): a022707.
15.	Pardo C A, Nabbout R, Galanopoulou A S. Mechanisms of epileptogenesis in pediatric epileptic syndromes: Rasmussen encephalitis, infantile spasms, and febrile infection-related epilepsy syndrome (FIRES). Neurotherapeutics, 2014, 11(2): 297-310.
16.	Pintaudi M, Eisermann MM, Ville D, et al. Can fever treat epileptic encephalopathies? Epilepsy Res, 2007, 77(1): 44-61.
17.	Jiang J, Dingledine R. Prostaglandin receptor EP2 in the crosshairs of anti-inflammation, anti-cancer, and neuroprotection. Trends Pharmacol Sci, 2013, 34(7): 413-423.
18.	Youn Y, Sung IK, Lee IG. The role of cytokines in seizures: interleukin (IL)-1beta, IL-1Ra, IL-8, and IL-10. Korean J Pediatr, 2013, 56(7): 271-274.
19.	Shiihara T, Miyashita M, Yoshizumi M, et al. Peripheral lymphocyte subset and serum cytokine profiles of patients with West syndrome. Brain Dev, 2010, 32(9): 695-702.
20.	Raffo E, Coppola A, Ono T, et al. A pulse rapamycin therapy for infantile spasms and associated cognitive decline. Neurobiol Dis, 2011, 43(2): 322-329.
21.	Barker-Haliski ML, Loscher W, White HS, et al. Neuroinflammation in epileptogenesis: Insights and translational perspectives from new models of epilepsy. Epilepsia, 2017, 58(Suppl 3): 39-47.
22.	Galanopoulou AS, Mowrey WB. Not all that glitters is gold: A guide to critical appraisal of animal drug trials in epilepsy. Epilepsia Open, 2016, 1(3-4): 86-101.
23.	Yamamoto H, Fukuda M, Miyamoto Y, et al. A new trial liposteroid (dexamethasone palmitate) therapy for intractable epileptic seizures in infancy. Brain Dev, 2007, 29(7): 421-424.
24.	Vezzani A, French J, Bartfai T, et al. The role of inflammation in epilepsy. Nat Rev Neurol, 2011, 7(1): 31-40.
25.	Dube CM, Ravizza T, Hamamura M, et al. Epileptogenesis provoked by prolonged experimental febrile seizures: mechanisms and biomarkers. J Neurosci, 2010, 30(22): 7484-7494.

1. Wilmshurst JM, Ibekwe RC, O'Callaghan FJK. Epileptic spasms - 175 years on: Trying to teach an old dog new tricks. Seizure, 2017, 44: 81-86.
2. Lee J, Lee JH, Yu H J, et al. Prognostic factors of infantile spasms: role of treatment options including a ketogenic diet. Brain Dev, 2013, 35(8): 821-826.
3. Ahmed R, Rubinger L, Go C, et al. Utility of additional dedicated high-resolution 3T MRI in children with medically refractory focal epilepsy. Epilepsy Res, 2018, 143: 113-119.
4. O'Callaghan FJ, Lux AL, Darke K, et al. The effect of lead time to treatment and of age of onset on developmental outcome at 4 years in infantile spasms: evidence from the United Kingdom Infantile Spasms Study. Epilepsia, 2011, 52(7): 1359-1364.
5. Mohamed BP, Scott RC, Desai N, et al. Seizure outcome in infantile spasms--a retrospective study. Epilepsia, 2011, 52(4): 746-752.
6. Graeber MB, Li W, Rodriguez ML. Role of microglia in CNS inflammation. FEBS Lett, 2011, 585(23): 3798-3805.
7. Vezzani A, Aronica E, Mazarati A, et al. Epilepsy and brain inflammation. Exp Neurol, 2013, 244(11-21).
8. Auvin S, Cilio MR, Vezzani A. Current understanding and neurobiology of epileptic encephalopathies. Neurobiol Dis, 2016, 92(Pt A): 72-89.
9. Bilbo SD, Schwarz JM. Early-life programming of later-life brain and behavior: a critical role for the immune system. Front Behav Neurosci, 2009, 3: 14.
10. Bilbo SD, Schwarz JM. The immune system and developmental programming of brain and behavior]. Front Neuroendocrinol, 2012, 33(3): 267-286.
11. Galic MA, Riazi K, Heida JG, et al. Postnatal inflammation increases seizure susceptibility in adult rats. J Neurosci, 2008, 28(27): 6904-6913.
12. Vezzani A, Maroso M, Balosso S, et al. IL-1 receptor/Toll-like receptor signaling in infection, inflammation, stress and neurodegeneration couples hyperexcitability and seizures. Brain Behav Immun, 2011, 25(7): 1281-1289.
13. Devinsky O, Vezzani A, Najjar S, et al. Glia and epilepsy: excitability and inflammation. Trends Neurosci, 2013, 36(3): 174-184.
14. Galanopoulou A S, Moshe S L. Neonatal and Infantile Epilepsy: Acquired and Genetic Models. Cold Spring Harb Perspect Med, 2015, 6(1): a022707.
15. Pardo C A, Nabbout R, Galanopoulou A S. Mechanisms of epileptogenesis in pediatric epileptic syndromes: Rasmussen encephalitis, infantile spasms, and febrile infection-related epilepsy syndrome (FIRES). Neurotherapeutics, 2014, 11(2): 297-310.
16. Pintaudi M, Eisermann MM, Ville D, et al. Can fever treat epileptic encephalopathies? Epilepsy Res, 2007, 77(1): 44-61.
17. Jiang J, Dingledine R. Prostaglandin receptor EP2 in the crosshairs of anti-inflammation, anti-cancer, and neuroprotection. Trends Pharmacol Sci, 2013, 34(7): 413-423.
18. Youn Y, Sung IK, Lee IG. The role of cytokines in seizures: interleukin (IL)-1beta, IL-1Ra, IL-8, and IL-10. Korean J Pediatr, 2013, 56(7): 271-274.
19. Shiihara T, Miyashita M, Yoshizumi M, et al. Peripheral lymphocyte subset and serum cytokine profiles of patients with West syndrome. Brain Dev, 2010, 32(9): 695-702.
20. Raffo E, Coppola A, Ono T, et al. A pulse rapamycin therapy for infantile spasms and associated cognitive decline. Neurobiol Dis, 2011, 43(2): 322-329.
21. Barker-Haliski ML, Loscher W, White HS, et al. Neuroinflammation in epileptogenesis: Insights and translational perspectives from new models of epilepsy. Epilepsia, 2017, 58(Suppl 3): 39-47.
22. Galanopoulou AS, Mowrey WB. Not all that glitters is gold: A guide to critical appraisal of animal drug trials in epilepsy. Epilepsia Open, 2016, 1(3-4): 86-101.
23. Yamamoto H, Fukuda M, Miyamoto Y, et al. A new trial liposteroid (dexamethasone palmitate) therapy for intractable epileptic seizures in infancy. Brain Dev, 2007, 29(7): 421-424.
24. Vezzani A, French J, Bartfai T, et al. The role of inflammation in epilepsy. Nat Rev Neurol, 2011, 7(1): 31-40.
25. Dube CM, Ravizza T, Hamamura M, et al. Epileptogenesis provoked by prolonged experimental febrile seizures: mechanisms and biomarkers. J Neurosci, 2010, 30(22): 7484-7494.

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神经炎症在婴儿痉挛发病机制中的研究进展

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