REDUCTION OF EXCITOTOXICITY-INDUCED BRAIN-DAMAGE BY THE COMPETITIVE NMDA ANTAGONIST CGP-40116 - A LONGITUDINAL-STUDY USING DIFFUSION-WEIGHTED IMAGING

The cerebroprotective properties of the competitive N-methyl-D-asparta te (NMDA) antagonist CGP 40116 were evaluated in a rat model of excito toxicity-induced brain damage using direct intrastriatal injection of quinolinic acid and subsequent (5 or 45 min later) i.p. administration of the drug. Diffusion-weighted magnetic resonance imaging (DWI) was used to follow the temporal lesion growth during the acute phase (4 h) and T-2-weighted MRI (T2WI) to quantify vasogenic edema extent 2 days later. For control animals, we found a rapid increase in lesion volum e during the first hour followed by a moderate growth over the followi ng hours. The DWI-visible hyperintensity was partially reversible afte r treatment with CGP 40116. The onset of action of CGP 40116 was immed iate. The final outcome (63% reduction of lesion volume within 2-4 h p ost-surgery) was independent of the time of drug administration. DWI d ata after 4 h correlated well with those obtained by T2WI 2 days later . DWI is a valuable method for early prediction of the outcome of ther apeutic interventions of excitotoxic insults.