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-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.
Laurent
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D
CIBA Ltd., Pharmaceuticals Division, CNS Pharmacology, Basel, Switzerland.
Eis
M
M
Sauer
D
D
Theilkaes
W
W
Allegrini
P R
PR
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000633:toxicity; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D004487:Edema / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009498:Neurotoxins / Q000633:toxicity*; D017378:Quinolinic Acid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013702:Temporal Lobe / Q000503:physiopathology; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; D015763:2-Amino-5-phosphonovalerate; D017378:Quinolinic Acid