The
neuroprotective effect of
talampanel, a negative allosteric modulator of alpha-amino-3-hydroxy-methyl-4-isoxazolyl-propionic
acid (
AMPA) receptors has been described previously. However, in these studies the histological changes and not the functional consequences of the brain damage were evaluated. The aim of present investigation was to analyze the sensorimotor function after
stroke and to test the influence of
talampanel (GYKI-53773, LY-300164) by 30-day monitoring in rats. After 1h
middle cerebral artery occlusion (MCAO) general 'well-being', neurological status, spontaneous motor activity, rotation, motor coordination, balancing, muscle strength and reaction time were followed for 1 month.
Talampanel (6 x 10 mg/kg i.p. given on the day of
stroke) improved the motor coordination in rotarod (p < 0.01) and beam walking (p < 0.01) tests, reduced the number of
stroke-induced rotations (p < 0.05), shortened the reflex time on the forelimb contralateral to
brain ischemia and improved the survival rate comparing with vehicle treated control. After
stroke, serious sensorimotor deficits appeared in rats but they showed partial spontaneous recovery after 30 days.
Talampanel treatment enhanced the rate of functional improvement without changing the morphology at the end of the experiment. Our results indicate that modulation of
AMPA receptors by
talampanel can be a promising therapeutic approach to the treatment of
stroke.