Effects of Ginko Biloba and caspase inhibitors on brain ischemia in the Mongolian Gerbil

J Neurosurg Sci. 2003 Sep;47(3):149-55.

Abstract

Aim: Data reported in previous studies and our own previous experience have led us to explore the mechanism of and the degree of protection afforded by Ginko Biloba in a model of cerebral ischemia in the Mongolian Gerbil evaluating histological and neurological effects in this rodent.

Methods: Mongolian Gerbils were divided into experimental groups: Group A consisted of animals subjected only to experimental ischemia; 5 minutes occlusion of the carotid arteries. Group B consisted of animals subjected to experimental ischemia and to a dose of Ginko Biloba, given intraperitoneally immediately before the surgical procedure. Group C consisted of animals subjected to experimental ischemia and to a dose of Ginko Biloba, given intraperitoneally immediately after the surgical procedure. Group D consisted of animals subjected to experimental ischemia and to a dose of the caspase inhibitors z-VAD.FMK and z-DEVD.FMK injected intracerebroventricularly through the right hemisphere before the surgical procedure. Group E consisted of animals subjected to experimental ischemia and to a dose of caspase inhibitors injected after the surgical procedure. Group F consisted of Sham-operated animals. Histological controls were done by H and E and the TUNEL method in the frontal cortex and caudate-putamen.

Results: The percentage of normal cells was not statistically significant at analysis with H and E, whereas the TUNEL method showed good protection with Ginko Biloba and caspase inhibitors, when the latter is given in the reperfusion phase. These data were in agreement with data obtained at neurological examination.

Conclusion: We could say that cellular morphology is in itself an untrustworthy tool for judging the effects of ischemia and protective drugs; the TUNEL method may add important information about the different components of cellular death; the reperfusion phase may be critical for apoptotic phenomena; Ginko Biloba might protect neurons of the frontal cortex from both necrotic and apoptotic death in this model of ischemia.

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Animals
  • Caspase Inhibitors*
  • Cerebral Cortex / pathology
  • Cysteine Proteinase Inhibitors / pharmacology
  • Drug Therapy, Combination
  • Gerbillinae
  • Ginkgo biloba*
  • In Situ Nick-End Labeling
  • Ischemic Attack, Transient / drug therapy*
  • Ischemic Attack, Transient / pathology
  • Male
  • Neuroprotective Agents / pharmacology
  • Phytotherapy*
  • Plant Preparations / pharmacology*

Substances

  • Amino Acid Chloromethyl Ketones
  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • Neuroprotective Agents
  • Plant Preparations
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone