Talampanel a non-competitive AMPA-antagonist attenuates caspase-3 dependent apoptosis in mouse brain after transient focal cerebral ischemia

Brain Res Bull. 2006 Jul 31;70(3):260-2. doi: 10.1016/j.brainresbull.2006.02.024. Epub 2006 Mar 31.

Abstract

Talampanel (IVAX) is a non-competitive AMPA-antagonist has a remarkable neuroprotection in different rodent stroke models. The focal cerebral ischemia in mice was induced by transient (60 min.) MCA occlusion and 48 h reperfusion and treated with talampanel (6 x 2 mg/kg, i.p.). The apoptotic and necrotic cells were analyzed by double immune histochemical staining on confocal laser microscope. The infarct size is decreased significantly by talampanel treatment (from 57.1+/-7.2mm(2) to 18.9+/-2.6 mm(2), p< 0.001). The number of TUNEL-positive cells localized mostly in the border zone of ischemic lesions is significantly decreased after talampanel treatment (from 962+/-13.0 to 604+/-6.9, p < 0.01). A strong, significant reduction of caspase-3 active cells was visualized. Talampanel as a neuroprotective drug candidate has a significant effect in mice transient MCA occlusion model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Benzodiazepines / therapeutic use*
  • Brain / drug effects*
  • Brain / pathology
  • Caspase 3
  • Caspases / drug effects*
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Infarction, Middle Cerebral Artery / drug therapy*
  • Infarction, Middle Cerebral Artery / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Neuroprotective Agents / therapeutic use*
  • Receptors, AMPA / antagonists & inhibitors

Substances

  • Neuroprotective Agents
  • Receptors, AMPA
  • Benzodiazepines
  • talampanel
  • Casp3 protein, mouse
  • Caspase 3
  • Caspases