title: Neuroprotective Effects of Hydrogen Sulfide Against Early Brain Injury and Secondary Cognitive Deficits Following Subarachnoid Hemorrhage.
abstract: 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.
authors.affiliation: 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.
authors.forename: Tong
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012, P.R. China.
authors.forename: Hansen
authors.initials: H
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Hao
authors.initials: H
authors.lastname: Xue
authors.affiliation: 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.
authors.forename: Jinsen
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.affiliation: 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.
authors.forename: Shaofeng
authors.initials: S
authors.lastname: Yan
authors.affiliation: Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012, P.R. China.
authors.forename: Shishi
authors.initials: S
authors.lastname: Bo
authors.affiliation: Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012, P.R. China.
authors.forename: Song
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yuan
authors.affiliation: 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.
authors.forename: Lin
authors.initials: L
authors.lastname: Deng
authors.affiliation: 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.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D001066:Appetite / Q000187:drug effects; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D001930:Brain Injuries / Q000209:etiology / Q000517:prevention & control*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis / Q000235:genetics; D006862:Hydrogen Sulfide / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D007859:Learning Disabilities / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000209:etiology / Q000517:prevention & control*; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017397:Prefrontal Cortex / Q000473:pathology; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016037:Single-Blind Method; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000473:pathology; D013440:Sulfides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D011355:Prodrugs; D013440:Sulfides; C025451:sodium bisulfide; D006862:Hydrogen Sulfide
keywords: brain-derived neurotrophic factor; cognitive deficits; early brain injury; hydrogen sulfide; subarachnoid hemorrhage
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