Coumestrol treatment prevents Na⁺, K⁺-ATPase inhibition and affords histological neuroprotection to male rats receiving cerebral global ischemia

Abstract

Objective: In this study, we investigated the possible mechanisms underlying the neuroprotective effects of coumestrol, a potent isoflavonoid with antioxidant activities and binding affinities for both estrogen receptors (ER) ER-alpha and ER-beta that are comparable to those of 17beta-estradiol, in a model of global ischemia in male subjects.

Methods: Wistar rats underwent global ischemia (10 minutes) or sham surgery and received a single intracerebroventricular (icv) infusion of 20 μg of coumestrol or vehicle 1 hour before ischemia or 0, 3, 6, or 24 hours after reperfusion.

Results: The data analysis revealed an extensive neuronal death in the CA1 hippocampal subfield at 7 days, and a significant decrease in the Na⁺, K⁺-ATPase activity at 1 and 24 hours after ischemia, and both injuries were attenuated by coumestrol administration.

Conclusions: Coumestrol treatment was effective in preventing neuronal loss in all times of administration as well as able to rescue the Na⁺, K⁺-ATPase activity, suggesting its potential benefits for either prevention or therapeutics use against cerebral ischemia in males.

Keywords:

• Cerebral ischemia
• Na⁺
• K⁺-ATPase
• Coumestrol
• Neuroprotection
• Hippocampus

Acknowledgements

This work was supported by the Conselho Nacional de Pesquisa e Desenvolvimento (CNPq) and also by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazilian Foundations.