Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebroprotection after administration of glutamate receptor antagonists has been well documented. The present study is intended to determine whether the non-competitive alpha-amino-3-hydroxy-methyl-4-isoxazolyl-propionic acid (AMPA) receptor antagonist talampanel, known as antiepileptic drug, has neuroprotective effects in stroke models in rodents. The infarct size was measured in three models of stroke by 2,3,5-triphenyltetrazolium chloride staining. Therapeutic time window was also examined in rats subjected to 1h middle cerebral artery occlusion. The degree of neuroprotection was tested in mice, using 1.5, 2 h or permanent middle cerebral artery occlusions. Effect on photochemically induced thrombosis was investigated in rats applying 30 min time window after brain irradiation. Talampanel reduced the infarct size by 47.3% (p<0.01) after a 30 min delay and 48.5% (p<0.01) after 2 h delay following middle cerebral artery occlusion in rats. In mice, talampanel reduced the extension of the infarcted tissue at the levels of striatum and hippocampus by 44.5% (p<0.05) and 39.3% (p<0.01) after 1.5 h transient ischemia and still caused 37.0% (p<0.05) and 37.0% (p<0.05) inhibitions when 2 h occlusion was applied. In photothrombosis talampanel showed a 40.1% (p<0.05) inhibition. Protective actions of talampanel in various stroke models, in rats and mice, suggest a possible therapeutic role of the compound in stroke patients.
 ...
PMID:The AMPA-antagonist talampanel is neuroprotective in rodent models of focal cerebral ischemia. 1592 43

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.
 ...
PMID:Talampanel improves the functional deficit after transient focal cerebral ischemia in rats. A 30-day follow up study. 1637 32