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条件性下调脑源性神经营养因子和酪氨酸激酶受体 B 可阻断人类颞叶癫痫海马的癫痫发生。

Conditional downregulation of brain- derived neurotrophic factor and tyrosine kinase receptor B blocks epileptogenesis in the human temporal lobe epilepsy hippocampus.

机构信息

Department of Neurology, The First Affiliated Hospital of Harbin Medical University, China.

出版信息

Neurol India. 2010 Jan-Feb;58(1):29-34. doi: 10.4103/0028-3886.60392.

Abstract

BACKGROUND

Brain-derived neurotrophic factor (BDNF) has been implicated as a potential therapeutic target in temporal lobe epilepsy (TLE). However, whether BDNF exerts an epileptogenic or antiepileptogenic function remains controversial.

MATERIALS AND METHODS

BDNF/tyrosine kinase receptor B (trkB) expression levels were comparatively assessed in the hippocampal tissue of TLE patients with (HS group) and without hippocampal sclerosis (non-HS group) as well as from non-epileptic controls.

RESULTS

Immunohistochemistry and immunoblot analysis revealed a marked increase in BDNF/trkB expression in the dentate gyrus and CA3 regions of HS and non-HS groups. The lack of any differences in expression levels was observed between HS and non-HS patients. Meanwhile, treatment with VPA (Valproic acid, anti-epileptic drug) resulted in a significant down-regulation of BDNF/trkB protein expression in sclerotic and non-sclerotic hippocampus (P < 0.001). In contrast, no marked change was noticed in VPA-untreated and OA-treated groups (sodium octanoate).

CONCLUSION

These results suggest that the up-regulation of BDNF/trkB pathway might be at least in part responsible for the epileptogenesis.

摘要

背景

脑源性神经营养因子(BDNF)已被认为是颞叶癫痫(TLE)的潜在治疗靶点。然而,BDNF 是否具有致痫或抗癫痫作用仍存在争议。

材料与方法

比较了 TLE 伴海马硬化(HS 组)和不伴海马硬化(非 HS 组)患者以及非癫痫对照者海马组织中的 BDNF/酪氨酸激酶受体 B(trkB)表达水平。

结果

免疫组织化学和免疫印迹分析显示,BDNF/trkB 在 HS 和非 HS 组的齿状回和 CA3 区表达明显增加。HS 和非 HS 患者之间未观察到表达水平的差异。同时,VPA(丙戊酸,抗癫痫药)治疗导致硬化和非硬化海马体中 BDNF/trkB 蛋白表达显著下调(P < 0.001)。相比之下,未治疗的 VPA 和 OA 治疗组(辛酸钠)没有明显变化。

结论

这些结果表明,BDNF/trkB 通路的上调至少部分是致痫的原因。

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