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脑源性神经营养因子对N-甲基-D-天冬氨酸诱导神经元死亡的眼睛的神经保护作用。

Neuroprotective effects of brain-derived neurotrophic factor in eyes with NMDA-induced neuronal death.

作者信息

Kido N, Tanihara H, Honjo M, Inatani M, Tatsuno T, Nakayama C, Honda Y

机构信息

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.

出版信息

Brain Res. 2000 Nov 24;884(1--2):59-67. doi: 10.1016/s0006-8993(00)02887-0.

Abstract

PURPOSE

To determine if brain-derived neurotrophic factor (BDNF) has a neuroprotective effect against N-methyl-D-aspartate (NMDA)-induced cell death in retina.

METHODS

NMDA was injected into the vitreous of rat eyes. NMDA-induced neuronal death was measured by morphometric analyses on cell counts of ganglion cell layer cells and thickness of retinal layers. Also, we conducted additional experiment using retrograde labeling with a fluorescent tracer (Fluoro-Gold) for exact counting of retinal ganglion cells (RGCs). In addition, intravitreal glutamate levels were measured with the use of a high-performance liquid chromatography (HPLC) system.

RESULTS

Morphometric analysis of retinal damage in NMDA-injected eyes showed that BDNF could protect inner retinal cells from glutamate receptor-mediated neuronal death. Also, counts of RGCs labeled with a fluorescent tracer showed that BDNF could protect RGCs from glutamate receptor-mediated neuronal death. Furthermore, measurements of intravitreal glutamate levels indicated an increase in this excitatory amino acid in the vitreous after NMDA injection.

CONCLUSIONS

Exogenous BDNF can protect inner retinal cells (possible RGCs and amacrine cells) from NMDA-induced neuronal death. However, increased intravitreal glutamate levels in response to NMDA-mediated neurotoxicity may augment retinal degeneration.

摘要

目的

确定脑源性神经营养因子(BDNF)对N-甲基-D-天冬氨酸(NMDA)诱导的视网膜细胞死亡是否具有神经保护作用。

方法

将NMDA注入大鼠眼玻璃体内。通过对神经节细胞层细胞计数和视网膜层厚度进行形态计量分析来测定NMDA诱导的神经元死亡。此外,我们使用荧光示踪剂(氟金)进行逆行标记以精确计数视网膜神经节细胞(RGC),进行了额外的实验。另外,使用高效液相色谱(HPLC)系统测量玻璃体内谷氨酸水平。

结果

对注射NMDA的眼睛视网膜损伤的形态计量分析表明,BDNF可以保护视网膜内层细胞免受谷氨酸受体介导的神经元死亡。同样,用荧光示踪剂标记的RGC计数表明,BDNF可以保护RGC免受谷氨酸受体介导的神经元死亡。此外,玻璃体内谷氨酸水平的测量表明,注射NMDA后玻璃体内这种兴奋性氨基酸增加。

结论

外源性BDNF可以保护视网膜内层细胞(可能是RGC和无长突细胞)免受NMDA诱导的神经元死亡。然而,响应NMDA介导的神经毒性而增加的玻璃体内谷氨酸水平可能会加剧视网膜变性。

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