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

Neurol Res. 2014 Mar;36(3):198-206. doi: 10.1179/1743132813Y.0000000286.

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,; Coumestrol,; Hippocampus; K+-ATPase,; Na+,; Neuroprotection,.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / enzymology
  • Brain Ischemia / pathology
  • CA1 Region, Hippocampal / drug effects*
  • CA1 Region, Hippocampal / pathology
  • Cell Death
  • Coumestrol / therapeutic use*
  • Male
  • Neuroprotective Agents / therapeutic use*
  • Pyramidal Cells / drug effects*
  • Rats
  • Rats, Wistar
  • Sodium-Potassium-Exchanging ATPase / metabolism*

Substances

  • Neuroprotective Agents
  • Sodium-Potassium-Exchanging ATPase
  • Coumestrol