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 journalArticle

Abstract

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
Volume125
Issue number1
DOIs
StatePublished - Jul 2018

Fingerprint

Nicotine
Brain
Brain Ischemia
Inflammation
Neutrophil Infiltration
Reactive Oxygen Species
Cerebrovascular Disorders
Middle Cerebral Artery Infarction
Transient Ischemic Attack
Brain Edema
Microglia
Metalloproteases
Encephalitis
Intercellular Adhesion Molecule-1
Tobacco Products
Reperfusion
Sprague Dawley Rats
Mitochondria
Oxidative Stress
Antioxidants

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Mito-Tempo prevents nicotine-induced exacerbation of ischemic brain damage. / Li, Chun; Sun, Hong; Xu, Guodong; McCarter, Kimberly D.; Li, Jiyu; Mayhan, William G.

In: Journal of Applied Physiology, Vol. 125, No. 1, 07.2018, p. 49-57.

Research output: Contribution to journalArticle

Li, Chun ; Sun, Hong ; Xu, Guodong ; McCarter, Kimberly D. ; Li, Jiyu ; Mayhan, William G. / Mito-Tempo prevents nicotine-induced exacerbation of ischemic brain damage. In: Journal of Applied Physiology. 2018 ; Vol. 125, No. 1. pp. 49-57.
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