Neuroimaging, Biochemical and Cellular Evidence of Protection by Mycophenolate Mofetil on Middle Cerebral Artery Occlusion Induced Injury in Rats

Eur J Pharmacol. 2012 Jun 5;684(1-3):71-8. doi: 10.1016/j.ejphar.2012.03.037. Epub 2012 Apr 1.

Abstract

Stroke is a major cause of mortality and disability worldwide. Presently, recombinant tissue plasminogen activator is the only approved drug for the management of acute ischemic stroke. However, it has limitations like narrow therapeutic window and increased risk of intracranial hemorrhage. In previous studies, immunosuppressive agents such as cyclosporine A and tacrolimus have shown neuroprotection by improving neurological functions and infarct volume in models of ischemic stroke. Therefore, the present study was designed to evaluate the effect of mycophenolate mofetil (MMF) on the cerebral ischemic injury in the middle cerebral artery occlusion (MCAo) model in rats. MCAo was carried out in male Wistar rats by inserting an intraluminal thread. One hour after MCAo, the animals were treated with MMF (50, 100, 200mg/kg, i.p.). Reperfusion was done after 2h of occlusion. Thirty minutes after reperfusion, animals were subjected to diffusion-weighted magnetic resonance imaging for assessment of neuroprotective effect of MMF. Twenty four hours after MCAo, motor performance was assessed and the animals were euthanized for estimation of brain malondialdehyde, glutathione, myeloperoxidase and nitric oxide levels. The effect of MMF on apoptosis was also evaluated. MMF significantly attenuated the percent infarct area, apparent diffusion coefficient and signal intensity as compared to a vehicle treated group. Treatment with MMF prevented the motor impairment and significantly reversed the changes in levels of malondialdehyde, glutathione, myeloperoxidase and nitric oxide. MMF treatment significantly reduced the apoptosis. Data of the present study indicate neuroprotective effect of MMF in the experimental model of ischemic stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Glutathione / metabolism
  • Hand Strength
  • Infarction, Middle Cerebral Artery / complications*
  • Magnetic Resonance Imaging*
  • Male
  • Malondialdehyde / metabolism
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / pharmacology
  • Neuroimaging*
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects
  • Peroxidase / metabolism
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / etiology*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control*
  • Rotarod Performance Test

Substances

  • Neuroprotective Agents
  • Malondialdehyde
  • Peroxidase
  • Glutathione
  • Mycophenolic Acid