Abstract

Introduction: A major problem exists in stroke management because of the sex differences in frequency and severity of disease and in treatment outcomes. Our recent studies demonstrated the potential of human umbilical cord blood-derived mesenchymal stem cells (HUCB-MSCs) in attenuating the post-stroke brain damage. Methods: Sprague-Dawley rats of both sexes were obtained and randomly assigned to various groups. Rats were subjected to a two-hour middle cerebral artery occlusion (MCAO) procedure by inserting a silicone rubber-coated monofilament suture followed by fourteen days of reperfusion. The body weight of rats on the day of the MCAO procedure and the size of the monofilament for male and female rats were standardized to obtain the same depth of post-stroke infarction. Previously standardized effective dose (0.25 million cells/animal) of HUCB-MSCs were intravenously injected via tail vein 24 hours post-MCAO to the designated groups of rats. Rats were subjected to neurological evaluation at various reperfusion time points by modified neurological severity scores ( mNSS), modified adhesive removal ( sticky-tape) beam walking and accelerating Rotarod performance tests. Results: The fourteen-day post-stroke survival period in males and females is approximately 20% and 70%, respectively. Females are more resistant to stroke-induced mortality. Although the difference in post-stroke percent survival is prominent in both sexes, there was no change in the body weight gain of both sexes. It was evident from the mNSS and sticky-tape tests that the magnitude of natural neurological recovery is the same in both sexes. However, the improvement in coordination and integration of motor function in females is better than males as evidenced by other tests. Stem cell treatment prevented mortality in males without any change in the treatment-induced body weight gain. Further, stem cell treatment improved neurological recovery in males, and the coordination and integration of motor function in females. Conclusions: Sex differences exist in post-stroke mortality and neurological function. Stem cell treatment improved neurological recovery and there was no sex difference in the magnitude of stem cell treatment improved neurological function

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