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新生大鼠缺氧性癫痫后海马 GABA 的下调。

Downregulation of hippocampal GABA after hypoxia-induced seizures in neonatal rats.

机构信息

Institute of Neurosciences, the Second Affiliated Hospital of Guangzhou Medical College, 250 Changgang Dong RD, Guangzhou 510260, People's Republic of China.

出版信息

Neurochem Res. 2011 Dec;36(12):2409-16. doi: 10.1007/s11064-011-0565-4. Epub 2011 Aug 11.

Abstract

This study aims to determine the expression of Gamma-aminobutyric acid (GABA) following hypoxia in neonatal rats and explore how it may increase susceptibility to epilepsy later in life. A modified model of neonatal hypoxia-induced epileptic susceptibility was simulated by 17 min of hypoxia (5% O(2) and 95% N(2)) in postnatal day (P) 10 rats. Hippocampal glutamate decarboxylase (GAD) and parvalbumin (PV) during the development with or without hypoxia were examined using immunohistochemistry. No detectable neuronal loss was observed in the hippocampus either immediately or 14 days after hypoxia. During the development GAD- and PV-immunoreactivity increased substantially during P 11-13 and reached mature expression in the control rats, and decreased significantly at different time points except for a transient increase during P 11-13 in the hypoxic groups. Our study indicates that downregulation of hippocampal GABA after hypoxia-induced seizures in neonatal rats may contribute to higher epileptic susceptibility in later life.

摘要

本研究旨在探讨γ-氨基丁酸(GABA)在新生大鼠缺氧后的表达情况,以及其如何增加生命后期癫痫易感性。通过在出生后第 10 天的大鼠中模拟 17 分钟的缺氧(5% O(2)和 95% N(2)),建立了一种改良的新生大鼠缺氧诱导癫痫易感性模型。采用免疫组织化学方法检测了缺氧或不缺氧时发育过程中的海马谷氨酸脱羧酶(GAD)和钙结合蛋白 Parvalbumin(PV)。无论是在缺氧后立即还是 14 天后,海马中均未观察到明显的神经元丢失。在发育过程中,GAD 和 PV 的免疫反应性在 P11-13 期间显著增加,并在对照组大鼠中达到成熟表达,而在缺氧组中,除了 P11-13 期间短暂增加外,在不同时间点均显著下降。我们的研究表明,新生大鼠缺氧后癫痫发作导致的海马 GABA 下调可能导致生命后期癫痫易感性增加。

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