期刊
JOURNAL OF NEUROSCIENCE RESEARCH
卷 95, 期 9, 页码 1838-1849出版社
WILEY
DOI: 10.1002/jnr.24016
关键词
intracerebral hemorrhage; cerebral cortex; motor dysfunction; neuroprotection; neuroinflammation; RRID:IMSR_JAX:000664; RRID:SCR_003070; RRID:SCR_ 013618; RRID:AB_2298772; RRID:AB_2630384; RRID: AB_2631098; RRID:AB_2336171; RRID:AB_2313606; RRID:SCR_002526; RRID:SCR_002798
资金
- Smoking Research Foundation [H28-75]
- JSPS KAKENHI [26670036, 16H04673, 16K15204]
- MEXT, Japan [H24-I02]
- Grants-in-Aid for Scientific Research [26670036, 16K15204, 16H04673, 16K08276, 17K15458] Funding Source: KAKEN
Intracerebral hemorrhage (ICH) is associated with diverse sets of neurological symptoms and prognosis, depending on the site of bleeding. Relative rate of hemorrhage occurring in the cerebral cortex (lobar hemorrhage) has been increasing, but there is no report on effective pharmacotherapeutic approaches for cortical hemorrhage either in preclinical or clinical studies. The present study aimed to establish an experimental model of cortical hemorrhage in mice for evaluation of effects of therapeutic drug candidates. Type VII collagenase at 0.015 U, injected into the parietal cortex, induced hemorrhage expanding into the whole layer of the posterior parts of the sensorimotor cortex in male C57BL/6 mice. Mice with ICH under these conditions exhibited significant motor deficits as revealed by beam-walking test. Daily administration of nicotine (1 and 2mg/kg), with the first injection given at 3 hr after induction of ICH, improved motor performance of mice in a dose-dependent manner, although nicotine did not alter the volume of hematoma. Immunohistochemical examinations revealed that the number of neurons was drastically decreased within the hematoma region. Nicotine at 2mg/kg partially but significantly increased the number of remaining neurons within the hematoma at 3 days after induction of ICH. ICH also resulted in inflammatory activation of microglia/macrophages in the perihematoma region, and nicotine (1 and 2mg/kg) significantly attenuated the increase of microglia. These results suggest that nicotine can provide a therapeutic effect on cortical hemorrhage, possibly via its neuroprotective and anti-inflammatory actions. (C) 2017 Wiley Periodicals, Inc.
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