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癫痫海马齿状回中光透射率模式的改变以及对AMPA诱导肿胀的抗性

Altered pattern of light transmittance and resistance to AMPA-induced swelling in the dentate gyrus of the epileptic hippocampus.

作者信息

Isokawa M

机构信息

Brain Research Institute and Department of Neurology, University of California, Los Angeles, USA.

出版信息

Hippocampus. 2000;10(6):663-72. doi: 10.1002/1098-1063(2000)10:6<663::AID-HIPO1004>3.0.CO;2-S.

Abstract

Glutamate receptor-mediated changes in light transmittance were imaged in the dentate gyri of the epileptic hippocampi, taken from patients with temporal lobe epilepsy and the rat pilocarpine model, to investigate epilepsy-associated alterations in activity-induced cell swelling. A static pattern of light transmittance corresponded to the layered structure of dentate gyrus and reflected epilepsy-associated alterations. Hypoosmotic stress produced more than 35% of dynamic changes in the increase of light transmittance as a reflection of osmotic swelling in the epileptic dentate gyri. This degree of increase was not different from the increase observed in control dentate gyri, suggesting that the capability of osmotically regulating cell volume was preserved in the epileptic dentate gyri. In contrast, alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) induced activity-dependent swelling and an increase in light transmittance by 60.5% in the control dentate gyri, whereas the degree of increase in the epileptic dentate gyri remained 17.9% in response to AMPA. Selective attenuation of light transmittance in response to AMPA in the epileptic but not control dentate gyri suggested a possible alteration in the swelling properties of the epileptic dentate gyri that are linked to the AMPA receptor activation. Surviving cells in the epileptic hippocampus may have a mechanism of downregulating neuronal activity-dependent swelling to maintain optimal cell volume during repeated network hyperexcitation in epilepsy.

摘要

在取自颞叶癫痫患者和大鼠匹罗卡品模型的癫痫海马齿状回中,对谷氨酸受体介导的光透射率变化进行成像,以研究癫痫相关的活动诱导细胞肿胀改变。光透射率的静态模式与齿状回的分层结构相对应,并反映了癫痫相关的改变。低渗应激导致癫痫齿状回中光透射率增加的动态变化超过35%,这反映了渗透性肿胀。这种增加程度与对照齿状回中观察到的增加无差异,表明癫痫齿状回中渗透压调节细胞体积的能力得以保留。相比之下,α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)在对照齿状回中诱导了活动依赖性肿胀以及光透射率增加60.5%,而癫痫齿状回中对AMPA的增加程度仅为17.9%。癫痫齿状回而非对照齿状回中对AMPA响应的光透射率选择性衰减,提示癫痫齿状回肿胀特性可能发生改变,这与AMPA受体激活有关。癫痫海马中的存活细胞可能具有下调神经元活动依赖性肿胀的机制,以在癫痫反复网络过度兴奋期间维持最佳细胞体积。

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