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作者

Zhang C. Xie R. Sun B. Zhang Z.

作者单位

Key Laboratory of Cerebral Microcirculalion in Universities of Shandong Province, Department of Neurology, Affiliated Hospital of Taishan Medical University, Taian, China

刊名

Chinese Journal of Cerebrovascular Diseases

年份

2018

卷号

Vol.15 No.11

页码

578-583

ISSN

1672-5921

关键词

JNJ16259685 Metabotropic glutamate receptor 1 Neuron Subarachnoid hemorrhage

摘要

Objective: To investigate the protective effect and its mechanism of metabotropic glutamate receptor 1 negative allosteric modulator JNJ 16259685 on neuron after subarachnoid hemorrhage in rats. Methods: Ninety SPF-grade SD male rats were selected. They were randomly divided into 3 groups: sham operation group ,SAH + placebo group , and SA H + JNJ16259685 group . A SAH model was induced by intravascular puncture. SAH + placebo group received intraperitoneal injection of aseptic water contain...更多

Objective: To investigate the protective effect and its mechanism of metabotropic glutamate receptor 1 negative allosteric modulator JNJ 16259685 on neuron after subarachnoid hemorrhage in rats. Methods: Ninety SPF-grade SD male rats were selected. They were randomly divided into 3 groups: sham operation group ,SAH + placebo group , and SA H + JNJ16259685 group . A SAH model was induced by intravascular puncture. SAH + placebo group received intraperitoneal injection of aseptic water containing 5% dimethyl sulfoxide at 2 ,24 and 48 h after operation. The SAH +JNJ group was intraperitoneally injected with 1 mg/kg JNJ16259685 . Garcia scoring criteria were used to assess neurological deficits at 72 h after SAH. Dry and wet weight method was used to detect brain edema. Evans Blue method was used to assess blood-brain barrier permeability. A calcium assay kit was used to detect the mitochondrial calcium ion concentration. Immunofluorescence staining was used to observe neuronal apoptosis. GraphPad 7. 0 software was used to conduct one-way analysis of variance in all indicators among the 3 groups. Results: Compared with the sham operation group,the Garcia score decreased in the SAH + placebo group. The water content in left and right hemispheres was 80. 5 ±0. 1% and 80. 3 ±0. 2% respectively,the Evans blue dye extravasation , basal cortical mitochondrial calcium ion concentration ,and neuronal apoptosis in basal cortex and hippocampus CA1 region increased ;and the Garcia score was significantly higher in the SAH +JNJ group than in the SAH + placebo group. Water content in left and right hemispheres was 79. 8 ± 0. 2% and 79. 3 ± 0. 1 % respectively, Evans blue dye extravasation ,basal cortex mitochondrial calcium ion concentration ,basal cortex and the number of neuronal apoptosis in hippocampal CA1 region reduced compared with the SAH + placebo group . Conclusion After SAH,JNJ16259685 relieves cerebral edema and reduces blood-brain barrier permeability,inhibits the increase of cortical mitochondrial calcium ion concentration,and reduces neuronal apoptosis,thereby exerting neuroprotective effects.收起

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