Grafting of striatal precursor cells into hippocampus shortly after status epilepticus restrains chronic temporal lobe epilepsy
Grafting of striatal precursor cells into hippocampus shortly after status epilepticus restrains chronic temporal lobe epilepsy
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DOI：
10.1016/j.expneurol.2008.04.040
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发表时间：
2008-08-01
影响因子：
5.3
通讯作者：
Shetty, Ashok K.
中科院分区：
文献类型：
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作者：
Hattiangady, Bharathi;Rao, Muddanna S.;Shetty, Ashok K.
癫痫持续状态（SE）通常发展为颞叶癫痫（TLE）的典型特征是复杂的部分癫痫发作。由于相当一部分TLE患者表现出对抗癫痫药物具有耐药性的慢性癫痫发作，因此有效减少se诱导的慢性癫痫的替代疗法具有重要意义。我们假设，在SE发生后不久，将经过适当处理的纹状体前体细胞移植到海马中，可以通过长期存活和向gaba能神经元的分化，有效地减少SE诱导的慢性癫痫。我们通过分级腹腔注射kainic酸诱导成年大鼠SE，在SE后4天双侧将纹状体前体移植物（用成纤维细胞生长因子-2和caspase抑制剂预处理）植入海马，并观察移植物对自发性复发性运动癫痫（SRMS）的长期影响。移植后9-12个月的分析显示，与接受假移植手术和仅癫痫对照的se大鼠相比，SRMS的总频率减少了67-89%。移植细胞的存活率与33%的注射细胞相似，69%的存活细胞分化为gaba -能神经元，包括表达calbindin、parvalbumin、calretinin和神经肽y的亚类。移植相当程度上保留了海马calbindin，但对异常苔藓纤维的发芽没有影响。本研究结果提供了新的证据，证明在癫痫发作后不久将适当处理的纹状体前体细胞移植到双侧海马能够长期有效地降低慢性癫痫期SRMS的发生频率。移植物中大量gaba能神经元的存在进一步表明，加强宿主海马的抑制控制可能是移植物介导的有益作用的基础。(C) 2008爱思唯尔公司版权所有。
Status epilepticus (SE) typically progresses into temporal lobe epilepsy (TLE) typified by complex partial seizures. Because sizable fraction of patients with TLE exhibit chronic seizures that are resistant to antiepileptic drugs, alternative therapies that are efficient for diminishing SE-induced chronic epilepsy have great significance. We hypothesize that bilateral grafting of appropriately treated striatal precursor cells into hippocampi shortly after SE is efficacious for diminishing SE-induced chronic epilepsy through long-term survival and differentiation into GABA-ergic neurons. We induced SE in adult rats via graded intraperitoneal injections of kainic acid, bilaterally placed grafts of striatal precursors (pre-treated with fibroblast growth factor-2 and caspase inhibitor) into hippocampi at 4 days post-SE, and examined long-term effects of grafting on spontaneous recurrent motor seizures (SRMS). Analyses at 9-12 months Post-grafting revealed that, the overall frequency of SRMS was 67-89% less than that observed in SE-rats that underwent sham-grafting Surgery and epilepsy-only controls. Graft cell Survival was similar to 33% of injected cells and similar to 69% of surviving cells differentiated into GABA-ergic neurons, which comprised subclasses expressing calbindin, parvalbumin, calretinin and neuropeptide Y. Grafting considerably preserved hippocampal calbindin but had no effects on aberrant mossy fiber Sprouting. The results provide novel evidence that bilateral grafting of appropriately treated striatal precursor cells into hippocampi shortly after SE is proficient for greatly reducing the frequency of SRMS on a long-term basis in the chronic epilepsy period. Presence of a large number of GABA-ergic neurons in grafts further suggests that strengthening of the inhibitory control in host hippocampi likely underlies the beneficial effects mediated by grafts. (C) 2008 Elsevier Inc. All rights reserved.