Allopurinol protects against ischemic insults in a mouse model of cortical microinfarction

Brain Res. 2015 Oct 5:1622:361-7. doi: 10.1016/j.brainres.2015.07.010. Epub 2015 Jul 14.

Abstract

Microinfarcts are common in patients with cognitive decline and dementia. Allopurinol (ALLO), a xanthine oxidase (XO) enzyme inhibitor, has been found to reduce proinflammatory molecules and oxidative stress in the vasculature. We here examined the effect of pre-treatment with allopurinol on the cortical microinfarction. C57BL/6J mice were subjected to a permanent single penetrating arteriole occlusion induced by two-photon laser irradiation. Infarction volume, the activation of glial cells and nitrosative stress in the ischemic brain was assessed using immunohistochemistry. Pre-treatment with ALLO achieved 42% reduction of infarct volume and significantly reduced microglia infiltration, astrocyte proliferation and nitrosative stress in the ischemic brain. These data indicate that ALLO protects against microinfarcts possibly through inhibition of nitrosative stress and attenuation of microglia infiltration as well as astrocytes reactivation.

Keywords: Allopurinol; Inflammation; Microinfarcts; Oxidative Stress; Two-photon laser-scanning microscope.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allopurinol / pharmacology*
  • Animals
  • Arterioles
  • Astrocytes / drug effects
  • Astrocytes / pathology
  • Astrocytes / physiology
  • Brain / drug effects*
  • Brain / pathology
  • Brain / physiopathology
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology
  • Cerebral Infarction / drug therapy*
  • Cerebral Infarction / pathology
  • Cerebral Infarction / physiopathology
  • Disease Models, Animal
  • Enzyme Inhibitors / pharmacology
  • Fluorescent Antibody Technique
  • Lasers
  • Male
  • Mice, Inbred C57BL
  • Microglia / drug effects
  • Microglia / pathology
  • Microglia / physiology
  • Neurons / drug effects
  • Neurons / pathology
  • Neurons / physiology
  • Neuroprotective Agents / pharmacology*
  • Xanthine Oxidase / antagonists & inhibitors
  • Xanthine Oxidase / metabolism

Substances

  • Enzyme Inhibitors
  • Neuroprotective Agents
  • Allopurinol
  • Xanthine Oxidase