Chronic nicotine exposure exacerbates transient focal cerebral ischemiainduced brain injury

Chun Li, Hong Sun, Denise M. Arrick, William G. Mayhan

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Tobacco smoking is a risk factor contributing to the development and progression of ischemic stroke. Among many chemicals in tobacco, nicotine may be a key contributor. We hypothesized that nicotine alters the balance between oxidant and antioxidant networks leading to an increase in brain injury following transient focal cerebral ischemia. Male Sprague-Dawley were treated with nicotine (2 or 4 mg•kg1•day1) for 4 wk via an implanted subcutaneous osmotic minipump and subjected to a 2-h middle cerebral artery occlusion (MCAO). Infarct size and neurological deficits were evaluated at 24 h of reperfusion. Superoxide levels were determined by lucigenin-enhanced chemiluminescence. Expression of oxidant and antioxidant proteins was measured using Western blot analysis. We found that chronic nicotine exposure significantly increased infarct size and worsened neurological deficits. In addition, nicotine significantly elevated superoxide levels of cerebral cortex under basal conditions. Transient focal cerebral ischemia produced an increase in superoxide levels of cerebral cortex in control group, but no further increase was found in the nicotine group. Furthermore, chronic nicotine exposure did not alter protein expression of NADPH oxidase but significantly decreased MnSOD and uncoupling protein-2 (UCP-2) in the cerebral cortex and cerebral arteries. Our findings suggest that nicotine-induced exacerbation in brain damage following transient focal cerebral ischemia may be related to a preexisting oxidative stress via decreasing of MnSOD and UCP-2.

Original languageEnglish (US)
Pages (from-to)328-333
Number of pages6
JournalJournal of Applied Physiology
Issue number3
StatePublished - Feb 1 2016
Externally publishedYes


  • Ischemia
  • MnSOD
  • Nicotine
  • Oxidative stress
  • Reperfusion
  • UCP-2

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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