Neuroprotective Effects of Hydrogen Sulfide Against Early Brain Injury and Secondary Cognitive Deficits Following Subarachnoid Hemorrhage
Tong Li
Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, 107#, Wenhua Xi Road, Jinan, Shandong Province, 250012 P.R. China
Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012 P.R. China
Search for more papers by this authorHansen Liu
Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012 P.R. China
Search for more papers by this authorHao Xue
Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, 107#, Wenhua Xi Road, Jinan, Shandong Province, 250012 P.R. China
Search for more papers by this authorJinsen Zhang
Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, 107#, Wenhua Xi Road, Jinan, Shandong Province, 250012 P.R. China
Search for more papers by this authorXiao Han
Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, 107#, Wenhua Xi Road, Jinan, Shandong Province, 250012 P.R. China
Search for more papers by this authorShaofeng Yan
Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, 107#, Wenhua Xi Road, Jinan, Shandong Province, 250012 P.R. China
Search for more papers by this authorShishi Bo
Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012 P.R. China
Search for more papers by this authorSong Liu
Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012 P.R. China
Search for more papers by this authorLin Yuan
Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012 P.R. China
Search for more papers by this authorLin Deng
Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, 107#, Wenhua Xi Road, Jinan, Shandong Province, 250012 P.R. China
Search for more papers by this authorCorresponding Author
Gang Li
Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, 107#, Wenhua Xi Road, Jinan, Shandong Province, 250012 P.R. China
Corresponding authors: Gang Li, Neurosurgery Department, Qilu Hospital, Shandong University, Wenhuaxilu Road, Jinan, Shandong Province 250012, P.R. China (E-mail: [email protected]) and Zhen Wang, Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, P.R. China (E-mail: [email protected])Search for more papers by this authorCorresponding Author
Zhen Wang
Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012 P.R. China
Corresponding authors: Gang Li, Neurosurgery Department, Qilu Hospital, Shandong University, Wenhuaxilu Road, Jinan, Shandong Province 250012, P.R. China (E-mail: [email protected]) and Zhen Wang, Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, P.R. China (E-mail: [email protected])Search for more papers by this authorTong Li
Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, 107#, Wenhua Xi Road, Jinan, Shandong Province, 250012 P.R. China
Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012 P.R. China
Search for more papers by this authorHansen Liu
Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012 P.R. China
Search for more papers by this authorHao Xue
Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, 107#, Wenhua Xi Road, Jinan, Shandong Province, 250012 P.R. China
Search for more papers by this authorJinsen Zhang
Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, 107#, Wenhua Xi Road, Jinan, Shandong Province, 250012 P.R. China
Search for more papers by this authorXiao Han
Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, 107#, Wenhua Xi Road, Jinan, Shandong Province, 250012 P.R. China
Search for more papers by this authorShaofeng Yan
Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, 107#, Wenhua Xi Road, Jinan, Shandong Province, 250012 P.R. China
Search for more papers by this authorShishi Bo
Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012 P.R. China
Search for more papers by this authorSong Liu
Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012 P.R. China
Search for more papers by this authorLin Yuan
Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012 P.R. China
Search for more papers by this authorLin Deng
Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, 107#, Wenhua Xi Road, Jinan, Shandong Province, 250012 P.R. China
Search for more papers by this authorCorresponding Author
Gang Li
Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, 107#, Wenhua Xi Road, Jinan, Shandong Province, 250012 P.R. China
Corresponding authors: Gang Li, Neurosurgery Department, Qilu Hospital, Shandong University, Wenhuaxilu Road, Jinan, Shandong Province 250012, P.R. China (E-mail: [email protected]) and Zhen Wang, Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, P.R. China (E-mail: [email protected])Search for more papers by this authorCorresponding Author
Zhen Wang
Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012 P.R. China
Corresponding authors: Gang Li, Neurosurgery Department, Qilu Hospital, Shandong University, Wenhuaxilu Road, Jinan, Shandong Province 250012, P.R. China (E-mail: [email protected]) and Zhen Wang, Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, P.R. China (E-mail: [email protected])Search for more papers by this authorAbstract
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.
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