COMBINATION CHEMOTHERAPY EXTENDS THE THERAPEUTIC WINDOW TO 60 MINUTESAFTER STROKE

We sought to extend the therapeutic window for acute stroke therapy us ing the combination of a glutamate antagonist and a GABA agonist, whic h 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 sali ne of 3.0, 2.3, 1.8, respectively), If muscimol was combined with MK-8 01 at lower doses of each drug, the combination was neuroprotective (p otency ratio of 4.2), Agonists of GABA-A, but not GABA-B, receptors bl ocked the toxic vacuolization seen in the cingulate and retrosplenial cortex after MK-801 treatment, Combination chemotherapy appears to ext end the time window for acute stroke therapy in rats to 1 h and to res ult in fewer side effects.