Neuroprotective Effects of Hydrogen Sulfide Against Early Brain Injury and Secondary Cognitive Deficits Following Subarachnoid Hemorrhage
Neuroprotective Effects of Hydrogen Sulfide Against Early Brain Injury and Secondary Cognitive Deficits Following Subarachnoid Hemorrhage
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硫化氢对蛛网膜下腔出血后早期脑损伤和继发性认知缺陷的神经保护作用
DOI：
10.1111/bpa.12361
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发表时间：
2017-01-01
期刊：
影响因子：
6.4
通讯作者：
Wang, Zhen
中科院分区：
文献类型：
--
作者：
Li, Tong;Liu, Hansen;Wang, Zhen
虽然硫化氢(H_2S)的神经保护作用已被多项研究证实，但在蛛网膜下腔出血(SAH)模型中，H_2S是否对早期脑损伤(EBI)和继发性认知功能障碍有保护作用尚不清楚。本研究旨在探讨硫化氢对蛛网膜下腔出血后急性脑损伤和神经行为改变的影响及其机制。大鼠SAH后2 h、6 h、24 h、46 h分别以5.6 mg/kg剂量腹腔注射硫化氢供体NaHS。结果表明，NaHS治疗SAH后48h，可明显改善SAH大鼠的脑水肿和神经行为功能，减轻前额叶皮质神经细胞死亡，并降低Bax/Bcl2比值，抑制caspase-3的激活。NaHS还促进了磷酸化Akt和磷酸化ERK的水平。此外，NaHS处理显著提高了脑源性神经营养因子(BDNF)和磷酸化CREB的水平。重要的是，在SAH后7天，给予NaHS改善了大鼠在Morris水迷宫测试中的学习和记忆能力。这些结果表明，NaHS作为外源性H_2S供体，可通过Akt/ERK相关的抗细胞凋亡途径，上调BDNF-CREB的表达，显著减轻SAH所致的EBI和认知功能障碍。
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.