期刊
NEUROBIOLOGY OF DISEASE
卷 30, 期 2, 页码 201-211出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2008.01.006
关键词
thrombin; mitogenic signaling; cell cycle; neuronal apoptosis; intracerebral hemorrhage; striatum
资金
- NINDS NIH HHS [R01 NS054652, R01 NS028167, NS056302, NS28167, R01 NS054652-02, R01 NS056302, NS054652, R01 NS054652-01A1, NS42774, R01 NS042774] Funding Source: Medline
Since Src kinase inhibitors decrease brain injury produced by intracerebral hemorrhage (ICH) and thrombin is activated following ICH, this study determined whether Src kinase inhibitors decrease thrombin-induced brain injury. Thrombin injections into adult rat striatum produced focal infarction and motor deficits. The Src kinase inhibitor PP2 decreased thrombin-induced Src activation, infarction in striatum and motor deficits in vivo. Thrombin applied to cultured post-mitotic striatal neurons caused: injury to axons and dendrites; many TUNEL positive neuronal nuclei; and re-entry into the cell cycle as manifested by cyclin D1 expression, induction of several other cell cycle genes and cyclin-dependent kinase 4 activation. PP2 dose-dependently attenuated thrombin-induced injury to the cultured neurons; and attenuated thrombin-induced neuronal cell cycle re-entry. These results are consistent with the hypotheses that Src kinase inhibitors decrease injury produced by ICH by decreasing thrombin activation of Src kinases and, at least in part, by decreasing Src induced cell cycle re-entry. (c) Published by Elsevier Inc.
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