Open AccessNeuroprotective Effects of Hydrogen Sulfide Against Early Brain Injury and Secondary Cognitive Deficits Following Subarachnoid Hemorrhage
Author(s) -
Li Tong,
Liu Hansen,
Xue Hao,
Zhang Jinsen,
Han Xiao,
Yan Shaofeng,
Bo Shishi,
Liu Song,
Yuan Lin,
Deng Lin,
Li Gang,
Wang Zhen
Publication year - 2017
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12361
Subject(s) - neuroprotection , creb , morris water navigation task , subarachnoid hemorrhage , medicine , neurotrophic factors , mapk/erk pathway , brain derived neurotrophic factor , anesthesia , pharmacology , protein kinase b , neuroscience , hippocampus , psychology , apoptosis , chemistry , signal transduction , receptor , biochemistry , transcription factor , gene
Although the neuroprotective effects of hydrogen sulfide (H 2 S) have been demonstrated in several studies, whether H 2 S 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 H 2 S on both acute brain injury and neurobehavioral changes as well as the underlying mechanisms after SAH. The H 2 S 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 H 2 S 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.