Talampanel improves the functional deficit after transient focal cerebral ischemia in rats. A 30-day follow up study.
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.
Erdo
Franciska
F
Department of Pharmacology, IVAX Drug Research Institute Ltd, P.O.B. 82, Budapest H-1325, Hungary. erdof2002@yahoo.de
Berzsenyi
Pál
P
Német
László
L
Andrási
Ferenc
F
D000818:Animals; D001569:Benzodiazepines / Q000627:therapeutic use*; D004195:Disease Models, Animal; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D008297:Male; D008991:Monitoring, Physiologic / Q000379:methods; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D012399:Rotation; D013997:Time Factors; D016138:Walking
D018696:Neuroprotective Agents; D018091:Receptors, AMPA; D001569:Benzodiazepines; C085266:talampanel