COMBINATION CHEMOTHERAPY EXTENDS THE THERAPEUTIC WINDOW TO 60 MINUTES AFTER STROKE

We sought to extend the therapeutic window for acute stroke therapy using the combination of a glutamate antagonist and a GABA agonist, which in prior studies was effective if given 5 min after stroke, We used a quantal bioassay to measure neuroprotective potency after injection of several thousand microspheres into the cerebral circulation of rats, The GABA-A agonist muscimol, but not MK-801, was effective if given 30, 45, or 60 min after embolization (potency ratio compared with saline of 3.0, 2.3, 1.8, respectively), If muscimol was combined with MK-801 at lower doses of each drug, the combination was neuroprotective (potency ratio of 4.2), Agonists of GABA-A, but not GABA-B, receptors blocked the toxic vacuolization seen in the cingulate and retrosplenial cortex after MK-801 treatment, Combination chemotherapy appears to extend the time window for acute stroke therapy in rats to 1 h and to result in fewer side effects.