RIVASTIGMINE, A BRAIN-SELECTIVE ACETYLCHOLINESTERASE INHIBITOR, AMELIORATES COGNITIVE AND MOTOR DEFICITS INDUCED BY CLOSED-HEAD INJURY IN THE MOUSE

The effects of Rivastigmine, a novel centrally-acting anticholinestera se agent, were evaluated on cerebral edema, neurological and motor def icits, and impairment of spatial memory induced in mice by closed-head injury (CHI), Severe injury was induced in the left hemisphere of mic e under ether anesthesia. Rivastigmine (1 or 2 mg/kg) or saline (10 ml /kg) was injected SC 5 min later, Rivastigmine (2 mg/kg) reduced cereb ral edema by at least 50% (p < 0.01), 24 h after CHI and accelerated t he recovery of motor function 7 and 14 days after CHI. Control mice (n = 24), previously trained to find the goal platform in a Morris water maze failed to recall or relearn its position for at least 11 days po st-injury, Those given a single injection of Rivastigmine (2 mg/kg) re gained their pre-test latencies by the third day after CHI, The neurop rotective effects of Rivastigmine on brain edema, neurological and mot or function, and performace in the Morris water maze were completely a ntagonized by simultaneous SC injection of either scopolamine (0.5 mg/ kg) or mecamylamine (2.5 mg/kg). The antagonists alone had no signific ant effect on any of these parameters, These data show that the reduct ion by Rivastigmine of the immediate and long-term sequelae of brain i njury are mediated by increased cholinergic activity at both muscarini c and nicotinic receptors.