Improved spatial memory, neurobehavioral outcomes, and neuroprotective effect after progesterone administration in ovariectomized rats with traumatic brain injury: Role of RU486 progesterone receptor antagonist

Document Type : Original Article

Authors

1 Neuroscience Research and Physiology Research Centers, Kerman University of Medical Sciences, Kerman, Iran

2 Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran

3 Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, Iran

4 Physiology Research Centers, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran

5 Department of Physiology, Bam University of Medical Sciences, Bam, Iran

6 Department of Psychology, Genetic Institute, Islamic Azad University- Zarand Branch, Kerman, Iran

Abstract

Objective(s): The contribution of classic progesterone receptors (PR) in interceding the neuroprotective efficacy of progesterone (P4) on the prevention of brain edema and long-time behavioral disturbances was assessed in traumatic brain injury (TBI).
Materials and Methods: Female Wistar rats were ovariectomized and apportioned into 6 groups: sham, TBI, oil, P4, vehicle, and RU486. P4 or oil was injected following TBI. The antagonist of PR (RU486) or DMSO was administered before TBI. The brain edema and destruction of the blood-brain barrier (BBB) were determined. Intracranial pressure (ICP), cerebral perfusion pressure (CPP), and beam walk (BW) task were evaluated previously and at various times post-trauma. Long-time locomotor and cognitive consequences were measured one day before and on days 3, 7, 14, and 21 after the trauma.
Results: RU486 eliminated the inhibitory effects of P4 on brain edema and BBB leakage (p <0.05, p <0.001, respectively). RU486 inhibited the decremental effect of P4 on ICP as well as the increasing effect of P4 on CPP (p <0.001) after TBI. Also, RU486 inhibited the effect of P4 on the increase in traversal time and reduction in vestibulomotor score in the BW task (p <0.001). TBI induced motor, cognitive, and anxiety-like disorders, which lasted for 3 weeks after TBI; but, P4 prevented these cognitive and behavioral abnormalities (p <0.05), and RU486 opposed this P4 effect (p <0.001).
Conclusion: The classic progesterone receptors have neuroprotective effects and prevent long-time behavioral and memory deficiency after brain trauma.

Keywords

References

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Iranian Journal of Basic Medical Sciences
Volume 24, Issue 3
March 2021
Pages 349-359

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