Neuroprotective properties of the non-peptidyl radical scavenger IAC in rats following transient focal cerebral ischemia

Brain Res. 2008 May 1:1207:174-81. doi: 10.1016/j.brainres.2008.02.027. Epub 2008 Feb 21.

Abstract

Experimental evidence suggests that reactive free radicals are generated during brain ischemia. We investigated the effect of a novel brain penetrant, low molecular weight, non-peptidyl carbon, oxygen- and nitrogen-centered radical scavenger, IAC, on infarct volume and sensory-motor performance in a rat transient middle cerebral artery occlusion model (tMCAO). Rats received 90 min tMCAO and treated with i.p. or i.v. injections of vehicle or IAC following tMCAO. Sensory-motor performance was evaluated by neuroscore tests (NS). Cerebral infarct volume was evaluated at 72 h after tMCAO. Rats treated with IAC i.p. (1 or 6 h after the onset of tMCAO) or i.v. (1 h after the onset of tMCAO) showed significant improvement in NS during the 3 or 21 day follow-up period when compared to vehicle treated rats. Cerebral infarct volumes were significantly decreased compared to vehicle in rats receiving IAC i.p. 1 h or 6 h after occlusion, approximately 30.5% decrease compared to vehicle, or i.v. 1 h after the onset of tMCAO, 48.6% decrease compared to vehicle. These results demonstrate that IAC has neuroprotective properties with a wide therapeutic window following tMCAO in rats. IAC could therefore be a candidate for the treatment of stroke.

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal
  • Cerebral Infarction / etiology
  • Cerebral Infarction / prevention & control
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Esters / therapeutic use*
  • Ischemic Attack, Transient / complications
  • Ischemic Attack, Transient / drug therapy*
  • Male
  • Neuroprotective Agents / therapeutic use*
  • Piperidines / therapeutic use*
  • Psychomotor Performance / drug effects
  • Psychomotor Performance / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Severity of Illness Index
  • Time Factors

Substances

  • Esters
  • Neuroprotective Agents
  • Piperidines
  • bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)decandioate