Abstract
Intracerebral hemorrhage (ICH) resulting from the leakage of blood into the brain parenchyma triggers severe tissue damage involving neurodegeneration and inflammation. Increasing lines of evidence indicate that the stimulation of central nicotinic acetylcholine receptors affords neuroprotection against various insults and also suppresses the proinflammatory activation of microglia. Therefore, the present study aimed to determine whether the administration of nicotine modifies the pathological consequences of ICH, using a mouse model of ICH induced by intrastriatal injection of collagenase. Daily intraperitoneal administration of nicotine (2 mg/kg), starting from 3 h after the induction of ICH, inhibited apoptosis and decreased the number of remaining striatal neurons at 3 days after the insult. We also found that nicotine administration increased the relative expression level of the antiapoptotic protein B cell lymphoma-2 versus that of the proapoptotic protein Bax in the brain. In addition, nicotine administration attenuated the activation of microglia/macrophages, infiltration of neutrophils, and increases in oxidative stress associated with ICH, without affecting hematoma expansion and brain edema. It is noteworthy that mice treated with nicotine exhibited improved sensorimotor performance and a marked increase in survival rate after ICH. These results indicate that nicotinic acetylcholine receptors may serve as a novel target for emergency therapy for ICH.
Footnotes
This work was supported by The Smoking Research Foundation [Grant H22-86, H23-90]; and The Ministry of Education, Culture, Sports, Science and Technology, Japan [Grants 20390026, 23117714].
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
doi:10.1124/jpet.111.182519.
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ABBREVIATIONS:
- ICH
- intracerebral hemorrhage
- Bcl-2
- B cell lymphoma-2
- MPO
- myeloperoxidase
- nAChR
- nicotinic acetylcholine receptor
- PBS
- phosphate-buffered saline
- TUNEL
- terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling.
- Received March 31, 2011.
- Accepted May 23, 2011.
- Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics
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