Suppressive effect of E-64c on ischemic degradation of cerebral proteins following occlusion of the middle cerebral artery in rats

Brain Res. 1990 Aug 27;526(1):177-9. doi: 10.1016/0006-8993(90)90269-h.


Microtubule-associated protein 2 (MAP2) levels in the left cerebral hemisphere decreased significantly 3 days after occlusion of the left middle cerebral artery in rats to 29 +/- 16.3% of control levels. Since MAP2 is one of the substrates of calpain, E-64c, a synthetic calpain inhibitor, was administered at a dose of 400 mg/kg twice a day for 3 days, with the first dose being given before the production of ischemia. This depletion was significantly inhibited in vivo by E-64c (P less than 0.05) to increase MAP2 levels to 55 +/- 25.7% of control levels. E-64c had no significant effect on the ischemia-induced depletion of myelin-associated glycoprotein. Sham-operated rats were used as controls. Our results suggest that calpain is partially involved in the degradation of MAP2, and that the use of calpain inhibitors can be a useful clinical approach to cerebral ischemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calpain / antagonists & inhibitors*
  • Cerebral Arteries
  • Immunoblotting
  • Ischemic Attack, Transient / drug therapy
  • Ischemic Attack, Transient / metabolism*
  • Leucine / analogs & derivatives*
  • Leucine / pharmacology
  • Male
  • Microtubule-Associated Proteins / metabolism*
  • Myelin Proteins / metabolism*
  • Myelin-Associated Glycoprotein
  • Rats
  • Rats, Inbred Strains


  • Microtubule-Associated Proteins
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • N-(N-(3-carboxyoxirane-2-carbonyl)leucyl)isoamylamine
  • Calpain
  • Leucine