Neuroprotective effect of Azadirachta indica on cerebral post-ischemic reperfusion and hypoperfusion in rats

Life Sci. 2005 Feb 4;76(12):1325-38. doi: 10.1016/j.lfs.2004.06.029. Epub 2005 Jan 18.

Abstract

We assessed the effect of Azadirachta indica (A. indica), a plant that has been reported to possess antioxidant, anti-inflammatory and anxiolytic properties, on cerebral reperfusion injury and long term cerebral hypoperfusion. When blood flow to brain region that has undergone critical period of ischemia is re-established, additional injury is to be expected from the reperfusion. In the present study, bilateral common carotid artery (BCCA) occlusion for 30 min followed by 45 min reperfusion resulted in increase in lipid peroxidation, superoxide dismutase (SOD) activity and fall in total tissue sulfhydryl (T-SH) groups. A. indica pretreatment (500 mg/kg/day x 7 days) attenuated the reperfusion induced enhanced lipid peroxidation, SOD activity and prevented fall in T-SH groups. Moreover, A.indica per se increased brain ascorbic acid level, which was unchanged during reperfusion insult. Long-term cerebral hypoperfusion induced by permanent BCCA occlusion has been reported to cause behavioral and histopathological abnormalities. In the present study, as tested by open field paradigm and Morris' water maze, a propensity towards anxiety and disturbances of learning/memory were observed in animals subjected to hypoperfusion for 2 weeks. A. indica (500 mg/kg/day x 15 days) significantly reduced these hypoperfusion induced functional disturbances. Reactive changes in brain histology like gliosis, perivascular lymphocytic infiltration, recruitment of macrophages and cellular edema following long term hypoperfusion were also attenuated effectively by A. indica. We conclude that our study provides an experimental evidence for possible neuroprotective potentiality of A. indica.

MeSH terms

  • Animals
  • Azadirachta / chemistry*
  • Behavior, Animal / drug effects
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Disease Models, Animal
  • Exploratory Behavior / drug effects
  • Ischemic Attack, Transient / drug therapy*
  • Ischemic Attack, Transient / metabolism
  • Ischemic Attack, Transient / pathology
  • Male
  • Maze Learning / drug effects
  • Neuroprotective Agents / therapeutic use*
  • Oxidative Stress / drug effects
  • Phytotherapy
  • Plant Extracts / therapeutic use*
  • Rats
  • Rats, Inbred Strains
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology

Substances

  • Neuroprotective Agents
  • Plant Extracts