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发育中大脑的神经发生与癫痫

Neurogenesis and epilepsy in the developing brain.

作者信息

Porter Brenda E

机构信息

The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

出版信息

Epilepsia. 2008 Jun;49 Suppl 5(Suppl 5):50-4. doi: 10.1111/j.1528-1167.2008.01637.x.

DOI:10.1111/j.1528-1167.2008.01637.x
PMID:18522600
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2700768/
Abstract

Multiple studies have highlighted how seizures induce different molecular, cellular, and physiologic consequences in an immature brain as compared to a mature brain. In keeping with these studies, seizures early in life alter dentate granule cell birth in different, and even opposing, fashion to adult seizure models (see Table 1). During the first week of rodent postnatal life, seizures decrease cell birth in the postictal period, but do not alter the maturation of newborn cells. Seizures during the second week of life have varied effects on dentate granule cell birth, either causing no change or increasing birth, and may promote a mild increase in neuronal survival. During the third and fourth weeks of life, seizures begin to increase cell birth similar to that seen in adult seizure models. Interestingly, animals that experienced seizure during the first month of life have an increase in cell birth during adulthood, opposite to the reported decrease in chronic animals experiencing a prolonged seizure as an adult. Children have more ongoing cell birth in the dentate gyrus than adults, and markers of cell division are further increased in children with refractory temporal lobe epilepsy. There are clear age-dependent differences in how seizures alter cell birth in the dentate gyrus both acutely and chronically. Future studies need to focus on how these changes in neurogenesis influence dentate gyrus function and what they imply for epileptogenesis and learning and memory impairments, so commonly found in children with temporal lobe epilepsy.

摘要

多项研究强调,与成熟大脑相比,癫痫发作在未成熟大脑中会引发不同的分子、细胞和生理后果。与这些研究一致的是,生命早期的癫痫发作以不同于甚至相反于成年癫痫模型的方式改变齿状颗粒细胞的生成(见表1)。在啮齿动物出生后的第一周,癫痫发作会在发作后期减少细胞生成,但不会改变新生细胞的成熟。出生后第二周的癫痫发作对齿状颗粒细胞生成有不同影响,要么没有变化,要么增加生成,并且可能会使神经元存活率略有增加。在出生后的第三和第四周,癫痫发作开始像在成年癫痫模型中那样增加细胞生成。有趣的是,在生命的第一个月经历过癫痫发作的动物在成年期细胞生成会增加,这与报道的成年后经历长时间癫痫发作的慢性动物细胞生成减少相反。儿童齿状回中正在进行的细胞生成比成年人更多,并且难治性颞叶癫痫儿童的细胞分裂标记物会进一步增加。癫痫发作在急性和慢性情况下如何改变齿状回中的细胞生成存在明显的年龄依赖性差异。未来的研究需要关注神经发生的这些变化如何影响齿状回功能,以及它们对癫痫发生、学习和记忆障碍意味着什么,而这些在颞叶癫痫儿童中很常见。

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