暴露于谷氨酸后，地卓西平、犬尿烯酸和NBQX对呼吸脑片水肿的调节作用。

Modulation of edema by dizocilpine, kynurenate, and NBQX in respiring brain slices after exposure to glutamate.

作者信息

Espanol M T, Xu Y, Litt L, Chang L H, James T L, Weinstein P R, Chan P H

机构信息

Anesthesia Department, University of California, San Francisco.

出版信息

Acta Neurochir Suppl (Wien). 1994;60:58-61. doi: 10.1007/978-3-7091-9334-1_15.

DOI:10.1007/978-3-7091-9334-1_15

PMID:7976656

Abstract

Brain edema caused by glutamate excitotoxicity was studied in well oxygenated neonatal cerebrocortical brain slices (350 mu thick). Slices exposed to 60 minutes of 2 mM glutamate, with or without glutamate antagonists (dizocilpine, kynurenate, or NBQX), were allowed to recover for 60 minutes. The protocol was identical to that in noninvasive multinuclear NMR spectroscopy studies (31P/1H/19F) of live slices. Percent water and swelling were determined invasively in isolated slices by wet and dry weight measurements before and after glutamate exposure. Edema was detectable within minutes in all experiments with glutamate exposures, but not in untreated control slices. Dizocilpine, kynurenate, and NBQX differently affected swelling, which correlated with PCr and ATP loss in separate NMR studies. Synaptic glutamate receptor activation appears to initiate events causing both edema and energy failure. Multiple glutamate receptor types seem to be involved. No glutamate antagonist provided greater protection against both edema and energy loss than dizocilpine. Dizocilpine might also block voltage-dependent Na+ channels, and provide protection via mechanisms other than NMDA-receptor dependent channel antagonism.

摘要

在充分氧合的新生大脑皮质脑片（350微米厚）中研究了由谷氨酸兴奋性毒性引起的脑水肿。将暴露于2 mM谷氨酸60分钟的脑片，无论有无谷氨酸拮抗剂（地佐环平、犬尿烯酸或NBQX），恢复60分钟。该方案与活脑片的无创多核磁共振波谱研究（31P/1H/19F）相同。通过在谷氨酸暴露前后对分离脑片进行湿重和干重测量，以侵入性方式确定水含量百分比和肿胀情况。在所有谷氨酸暴露实验中，数分钟内即可检测到水肿，但未处理的对照脑片中未检测到。地佐环平、犬尿烯酸和NBQX对肿胀的影响不同，这与单独核磁共振研究中磷酸肌酸（PCr）和三磷酸腺苷（ATP）的损失相关。突触谷氨酸受体激活似乎引发了导致水肿和能量衰竭的事件。似乎涉及多种谷氨酸受体类型。没有一种谷氨酸拮抗剂比地佐环平对水肿和能量损失提供更好的保护。地佐环平还可能阻断电压依赖性钠通道，并通过除NMDA受体依赖性通道拮抗作用以外的机制提供保护。