cgp-37849 and Edema

The cerebroprotective properties of the competitive N-methyl-D-aspartate (NMDA) antagonist CGP 40116 were evaluated in a rat model of excitotoxicity-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 T2-weighted MRI (T2WI) to quantify vasogenic edema extent 2 days later. For control animals, we found a rapid increase in lesion volume during the first hour followed by a moderate growth over the following hours. The DWI-visible hyperintensity was partially reversible after treatment with CGP 40116. The onset of action of CGP 40116 was immediate. The final outcome (63% reduction of lesion volume within 2-4 h post-surgery) was independent of the time of drug administration. DWI data 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 therapeutic interventions of excitotoxic insults.

Topics: 2-Amino-5-phosphonovalerate; Animals; Brain Chemistry; Edema; Excitatory Amino Acid Antagonists; Longitudinal Studies; Magnetic Resonance Imaging; Male; Neurotoxins; Quinolinic Acid; Rats; Rats, Inbred Strains; Receptors, N-Methyl-D-Aspartate; Temporal Lobe; Time Factors