Long term cerebroprotective effects of dexanabinol in a model of focal cerebral ischemia

In order to test the long-term cerebroprotective effects of dexanabinol, a synthetic non-competitive NMDA antagonist that also has anti-TNF alpha effe cts, spontaneously hypertensive rats underwent permanent middle cerebral ar tery occlusion (PMCAO). Rats were given vehicle or dexanabinol (3.5 mg/kg) 1. 3 or 6 h after PMCAO. The research consisted of 2 stages. In the short-t erm set of experiments animals (n=5/group). were tested with a motor disabi lity scale 24 h post PMCAO, then sacrificed and the infarct volume was meas ured using 2,3.5-Triphenylterrazolium chloride (TTC) staining. In the long- term set of experiments the rats (n=7/group) were examined daily with a mot or disability scale up to 30 days after PMCAO and then sacrificed and infar ct volumes were determined using TTC staining. Motor scores were significan tly improved in the dexanabinol treated rats (P<0.05 for all groups) at all the time points examined. Infarct volumes were significantly reduced 24 h after PMCAO in the groups treated 1 or 3 h, but not 6 h after PMCAO compare d with vehicle (Mean<plus/minus>S.D., 11.5 +/-2.02, 12 +/-3.2 and 14.4 +/-2 .4% vs. 20.8 +/-1.3% hemispheric volume respectively). The lesions remained significantly smaller in the dexanabinol groups 30 days after PMCAO (Mean +/-S.D., 24.39 +/-1.9% vs. 8.1 +/-0.6, 11.1 +/-2.3 and 13.8 +/-2.5% hemisph eric volume in animals treated with vehicle vs. dexanabinol 1, 3 or 6 h aft er PMCAO respectively: P<0.05 for all). In conclusion, the extended therape utic window and the multi-mechanistic durable neuroprotective effects of de xanabinol make it a promising candidate for Future stroke therapy. (C) 2001 Elsevier Science B.V. All rights reserved.