title: Impaired adult hippocampal neurogenesis and cognitive ability in a mouse model of intrastriatal hemorrhage.
abstract: Thrombin released by hematoma is an important mediator of the secondary injury of intracerebral hemorrhage (ICH), however, the effect of thrombin on adult neurogenesis and cognitive ability remains elusive. In this study, intrastriatal injection of 0.05 U thrombin didn't affect the neurogenesis at the subgranular zone (SGZ), which was distal to the injection site. 0.1 U thrombin increased the 5-bromo-2-deoxyuridine(+) (BrdU(+), S-phase proliferating cells)/doublecortin(+) (DCX(+), immature neurons) double labelled neurons, but decreased BrdU(+)/NeuN(+) double labelled mature neurons. Higher doses of thrombin (1 U, 2 U, and 5 U) significantly decreased the BrdU(+)/DCX(+) and BrdU(+)/NeuN(+) double labelled cells. After 1 U thrombin injection, cell apoptosis was found at the dentate gyrus of hippocampus at 3-24 h, but not 5 d post-injury. Thrombin infusion (1 U) induced spatial memory deficits in Morris water maze test; whereas, hirudin, the thrombin antagonist, significantly reversed both neurogenesis loss and spatial learning and memory impairment. In conclusion, at least at short term (5 days) after striatum ICH, the effect of high dose of thrombin on neurogenesis of SGZ, and the spatial learning and memory ability, is detrimental.
authors.affiliation: Department of Neurological, Chinese PLA General Hospital, No. 28, Fuxing Road, Haidian District, Beijing 100036, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Telemedicine Center, Chinese PLA General Hospital, No. 28, Fuxing Road, Haidian District, Beijing 100036, China. Electronic address: zmk301@hotmail.com.
authors.forename: Meikui
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Telemedicine Center, Chinese PLA General Hospital, No. 28, Fuxing Road, Haidian District, Beijing 100036, China.
authors.forename: Xiaoni
authors.initials: X
authors.lastname: Kang
authors.affiliation: Department of Telemedicine Center, Chinese PLA General Hospital, No. 28, Fuxing Road, Haidian District, Beijing 100036, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department Students Brigade, The Second Military Medical University, No. 800, Xiangyin Road, Shanghai 200433, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Telemedicine Center, Chinese PLA General Hospital, No. 28, Fuxing Road, Haidian District, Beijing 100036, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Telemedicine Center, Chinese PLA General Hospital, No. 28, Fuxing Road, Haidian District, Beijing 100036, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002543:Cerebral Hemorrhage / Q000150:complications / Q000473:pathology* / Q000523:psychology; D003072:Cognition Disorders / Q000209:etiology / Q000523:psychology*; D003342:Corpus Striatum / Q000473:pathology*; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000473:pathology*; D008297:Male; D018782:Maze Learning; D008568:Memory; D008810:Mice, Inbred C57BL; D009048:Motor Skills; D055495:Neurogenesis; D009474:Neurons / Q000473:pathology; D013917:Thrombin / Q000378:metabolism / Q000494:pharmacology
chemical_list: C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D013917:Thrombin
keywords: Doublecortin; Hirudin; Intrastriatal hemorrhage; Neurogenesis