血脑屏障
化学
内分泌学
海马体
内科学
高同型半胱氨酸血症
基质金属蛋白酶
神经保护
皮质扩散性抑郁症
药理学
同型半胱氨酸
埃文斯蓝
医学
生物化学
中枢神经系统
偏头痛
作者
Mohit Kumar,Rajat Sandhir
标识
DOI:10.1080/00207454.2020.1860967
摘要
Backgroud: Hyperhomocysteinemia (HHcy) is implicated in various neurovascular disorders including vascular dementia, subarachnoid hemorrhage and stroke. Elevated homocysteine (Hcy) levels are associated with increased oxidative stress and compromised blood-brain barrier (BBB) integrity. Hydrogen sulfide (H2S) has recently emerged as potent neuroprotective molecule in various neurological conditions including those associated with HHcy. The present study evaluates the protective effect of sodium hydrogen sulfide (NaHS; a source of H2S) on HHcy-induced BBB dysfunction and underpin molecular mechanisms.Materials and methods: Supplementation of NaHS restored the increased BBB permeability in the cortex and hippocampus of HHcy animals assessed in terms of diffused sodium fluorescein and Evans blue tracer dyes in the brain. Activity of matrix metalloproteinases (MMPs) assessed by gelatinase activity and in situ gelatinase assay was restored to the normal in the cortex and hippocampus of HHcy animals supplemented with NaHS.Results: Application of gelatin zymography revealed that specifically MMP-9 activity was increased in the cortex and hippocampus of HHcy animals, which was inhibited by NaHS supplementation. Real-time RT-PCR analysis showed that NaHS administration also decreased mRNA expression of MMP-9 in the hippocampus of HHcy animals. NaHS supplementation was further observed to reduce water retention in the brain regions of Hcy treated animals.Conclusion: Taken together, these findings suggest that NaHS supplementation ameliorates HHcy-induced BBB permeability and brain edema by inhibiting the mRNA expression and activity of MMP-9. Therefore, H2S and H2S releasing drugs may be used as a novel therapeutic approach to treat HHcy-associated neurovascular disorders.
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