Mito-Tempo prevents nicotine-induced exacerbation of ischemic brain damage

Chun Li, Hong Sun, Guodong Xu, Kimberly D. McCarter, Jiyu Li, William G. Mayhan

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Nicotine may contribute to the pathogenesis of cerebrovascular disease via the generation of reactive oxygen species (ROS). Overproduction of ROS leads to brain damage by intensifying postischemic inflammation. Our goal was to determine the effect of Mito-Tempo, a mitochondria-targeted antioxidant, on ischemic brain damage and postischemic inflammation during chronic exposure to nicotine. Male Sprague-Dawley rats were divided into four groups: control, nicotine, Mito-Tempo-treated control, and Mito-Tempo-treated nicotine. Nicotine (2 mg·kg1·day1) was administered via an osmotic minipump for 4 wk. Mito-Tempo (0.7 mg·kg1·day1 ip) was given for 7 days before cerebral ischemia. Transient focal cerebral ischemia was induced by occlusion of the middle cerebral artery for 2 h. Brain damage and inflammation were evaluated after 24 h of reperfusion by measuring infarct volume, expression of adhesion molecules, activity of matrix metalloprotei-nase, brain edema, microglial activation, and neutrophil infiltration. Nicotine exacerbated infarct volume and worsened neurological deficits. Nicotine did not alter baseline ICAM-1 expression, matrix metallopeptidase-2 activity, microglia activation, or neutrophil infiltration but increased these parameters after cerebral ischemia. Mito-Tempo did not have an effect in control rats but prevented the chronic nicotine-induced augmentation of ischemic brain damage and postischemic inflammation. We suggest that nicotine increases brain damage following cerebral ischemia via an increase in mitochondrial oxidative stress, which, in turn, contributes to postischemic inflammation. NEW & NOTEWORTHY Our findings have important implications for the understanding of mechanisms contributing to increased susceptibility of the brain to damage in smokers and users of nicotine-containing tobacco products.

Original languageEnglish (US)
Pages (from-to)49-57
Number of pages9
JournalJournal of Applied Physiology
Issue number1
StatePublished - Jul 2018
Externally publishedYes


  • Inflammation
  • Ischemia-reperfusion
  • Microglia
  • Neutrophils
  • Nicotine

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


Dive into the research topics of 'Mito-Tempo prevents nicotine-induced exacerbation of ischemic brain damage'. Together they form a unique fingerprint.

Cite this