PROTECTION OF BRAIN MITOCHONDRIA AGAINST MICRO STROKE-INDUCED INJURY: A STUDY OF ETHYLMETHYLHYDROXYPYRIDINE SUCCINATE IN EXPERIMENTAL MODEL USING TWO PHOTON LASER FLUORESCENT MICROSCOPY

Abstract

Objective. Mitochondrial injury plays a central role in neuronal death following ischemic stroke. In the present study, we investigated effects of ethylmethylhydroxypyridine succinate on a microstroke-induced mitochondria swelling, a hallmark of mitochondrial injury.Materials and Methods. Ischemic microstroke was induced in Thy1-CFP-MitoS mice expressing cyano fluorescent protein (CFP) in brain mitochondria by impulse infrared laser. Ethylmethylhydroxypyridine succinate 25 mg/kg or saline (control) were administered i.p. at 30 min after the stroke onset. A period of observation was 48 h. Brain images were obtained by two photon laser fluorescent microscopy and analyzed using a software developed in Neurotar Ltd (Finland). Nonparametric Mann-Whitney-Wilcoxon test was used for te statistical analysis of results.Results. Microstroke resulted in mitochondria swelling, i.e. injury, in the zone surrounding the thrombus. The most profound changes of mitochondrial morphology were observed at 2 h from the stroke onset. Ethylmethylhydroxypyridine succinate significantly reduces the stroke-induced swelling at 1 h (p<0.05) and 2 h (p<0.05), as compared to the control.Conclusion. These results suggest that ethylmethylhydroxypyridine succinate significantly protects brain mitochondria against microstroke-induced injury.

Keywords

• mitochondria
• ischemic stroke
• ethylmethylhydroxypyridine succinate
• fluorescent microscopy