OBJECTIVE
To compare the effects of Mexidol, Cerebrolysin, and Cortexin on the levels of brain-derived neurotrophic factor (BDNF), tumor necrosis factor-alpha (TNFα), and apoptosis markers in the rat brain following middle cerebral artery (MCA) occlusion-reperfusion.
MATERIAL AND METHODS
The study was performed on male Wistar rats. Right MCA occlusion-reperfusion was modeled using the method of J. Koizumi (1986). The occlusion duration was 60 minutes (1 hour). At the onset of reperfusion, animals were administered a single intravenous injection of either saline (control), or Mexidol (ethylmethylhydroxypyridine succinate) intravenously at a dose of 50 mg/kg, or Cerebrolysin intraperitoneally at a dose of 215 mg/kg, or Cortexin intraperitoneally at a dose of 1 mg/kg. Twenty-four hours after the start of reperfusion, the brain lesion volume was analyzed after staining with a 1% solution of 2.3,5-triphenyltetrazolium chloride. Western blotting was used to assess the levels of BDNF, TNFα, and apoptosis markers (Fas, bax, caspase 3) in the ischemic hemisphere. Five animals were included in each group for biochemical studies.
RESULTS
In the MCA occlusion-reperfusion model, the necrosis volume in the affected hemisphere of control animals was 38.16±5.98%. Mexidol reduced the necrosis volume to 20.48±2.33% (p<0.001), Cerebrolysin — to 32.57±3.31% (p=0.176), Cortexin — to 32.75±4.91% (p=0.198). Modeling the pathology triggered the development of neuroinflammation — an increase in TNFα content, activation of apoptosis — increased levels of Fas, bax, and caspase 3, and did not affect the BDNF level. Administration of Mexidol increased the BDNF level in the ischemic hemisphere and reduced the content of Fas, bax, caspase 3, and TNFα. Cerebrolysin had a similar effect, although less pronounced. Cortexin did not affect the BDNF level but reduced the content of TNFα, Fas, and bax.
CONCLUSION
Thus, when administered at the onset of reperfusion following MCA occlusion, Mexidol exerts the most pronounced cerebroprotective effect, stimulating neurogenesis and suppressing the development of neuroinflammation and apoptosis.
