Neuroprotective Effects of Hydrogen Sulfide Against Early Brain Injury and Secondary Cognitive Deficits Following Subarachnoid Hemorrhage

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• 作者：Tong Li ; Hansen Liu ; Hao Xue ; Jinsen Zhang ; Xiao Han ; Shaofeng Yan ; Shishi Bo ; Song Liu ; Lin Yuan ; Lin Deng ; Gang Li and Zhen Wang
• 刊名：Brain Pathology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：27
• 期：1
• 页码：51-63
• 全文大小：883K
• ISSN：1750-3639

文摘

Although the neuroprotective effects of hydrogen sulfide (H₂S) have been demonstrated in several studies, whether H₂S protects against early brain injury (EBI) and secondary cognitive dysfunction in subarachnoid hemorrhage (SAH) model remains unknown. This study was undertaken to evaluate the influence of H₂S on both acute brain injury and neurobehavioral changes as well as the underlying mechanisms after SAH. The H₂S donor, NaHS, was administered via an intraperitoneal injection at a dose of 5.6 mg/kg at 2 h, 6 h, 24 h, and 46 h after SAH in rat model. The results showed that NaHS treatment significantly improved brain edema and neurobehavioral function, and attenuated neuronal cell death in the prefrontal cortex, associated with a decrease in Bax/Bcl-2 ratio and suppression of caspase-3 activation at 48 h after SAH. NaHS also promoted phospho-Akt and phospho-ERK levels. Furthermore, NaHS treatment significantly enhanced the levels of brain-derived neurotrophic factor (BDNF) and phospho-CREB. Importantly, NaHS administration improved learning and memory performance in the Morris water maze test at 7 days post-SAH in rats. These results demonstrated that NaHS, as an exogenous H₂S donor, could significantly alleviate the development of EBI and cognitive dysfunction induced by SAH via Akt/ERK-related antiapoptosis pathway, and upregulating BDNF-CREB expression.