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

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 o...

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Main Authors: Ladan Amirkhosravi, Mohammad Khaksari, Vahid Sheibani, Nader Shahrokhi, Mohammad navid Ebrahimi, Sedigheh Amiresmaili, Neda Salmani
Format: Article
Language:English
Published: Mashhad University of Medical Sciences 2021-03-01
Series:Iranian Journal of Basic Medical Sciences
Subjects:
Online Access:https://ijbms.mums.ac.ir/article_17461_aa211a998b5641288b9f79a275600712.pdf
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author Ladan Amirkhosravi
Mohammad Khaksari
Vahid Sheibani
Nader Shahrokhi
Mohammad navid Ebrahimi
Sedigheh Amiresmaili
Neda Salmani
author_facet Ladan Amirkhosravi
Mohammad Khaksari
Vahid Sheibani
Nader Shahrokhi
Mohammad navid Ebrahimi
Sedigheh Amiresmaili
Neda Salmani
author_sort Ladan Amirkhosravi
collection DOAJ
description 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.
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spelling doaj.art-4c96c027290e4deab732932d8bee39b82022-12-21T20:14:35ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742021-03-0124334935910.22038/ijbms.2021.50973.1159117461Improved spatial memory, neurobehavioral outcomes, and neuroprotective effect after progesterone administration in ovariectomized rats with traumatic brain injury: Role of RU486 progesterone receptor antagonistLadan Amirkhosravi0Mohammad Khaksari1Vahid Sheibani2Nader Shahrokhi3Mohammad navid Ebrahimi4Sedigheh Amiresmaili5Neda Salmani6Neuroscience Research and Physiology Research Centers, Kerman University of Medical Sciences, Kerman, IranEndocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, IranNeuroscience Research Center, Kerman University of Medical Sciences, Kerman, IranPhysiology Research Centers, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, IranNeuroscience Research and Physiology Research Centers, Kerman University of Medical Sciences, Kerman, IranDepartment of Physiology, Bam University of Medical Sciences, Bam, IranDepartment of Psychology, Genetic Institute, Islamic Azad University- Zarand Branch, Kerman, IranObjective(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.https://ijbms.mums.ac.ir/article_17461_aa211a998b5641288b9f79a275600712.pdfbehavioral disordersmifepristoneneuroprotectionprogesteronespatial memorytbi
spellingShingle Ladan Amirkhosravi
Mohammad Khaksari
Vahid Sheibani
Nader Shahrokhi
Mohammad navid Ebrahimi
Sedigheh Amiresmaili
Neda Salmani
Improved spatial memory, neurobehavioral outcomes, and neuroprotective effect after progesterone administration in ovariectomized rats with traumatic brain injury: Role of RU486 progesterone receptor antagonist
Iranian Journal of Basic Medical Sciences
behavioral disorders
mifepristone
neuroprotection
progesterone
spatial memory
tbi
title Improved spatial memory, neurobehavioral outcomes, and neuroprotective effect after progesterone administration in ovariectomized rats with traumatic brain injury: Role of RU486 progesterone receptor antagonist
title_full Improved spatial memory, neurobehavioral outcomes, and neuroprotective effect after progesterone administration in ovariectomized rats with traumatic brain injury: Role of RU486 progesterone receptor antagonist
title_fullStr Improved spatial memory, neurobehavioral outcomes, and neuroprotective effect after progesterone administration in ovariectomized rats with traumatic brain injury: Role of RU486 progesterone receptor antagonist
title_full_unstemmed Improved spatial memory, neurobehavioral outcomes, and neuroprotective effect after progesterone administration in ovariectomized rats with traumatic brain injury: Role of RU486 progesterone receptor antagonist
title_short Improved spatial memory, neurobehavioral outcomes, and neuroprotective effect after progesterone administration in ovariectomized rats with traumatic brain injury: Role of RU486 progesterone receptor antagonist
title_sort improved spatial memory neurobehavioral outcomes and neuroprotective effect after progesterone administration in ovariectomized rats with traumatic brain injury role of ru486 progesterone receptor antagonist
topic behavioral disorders
mifepristone
neuroprotection
progesterone
spatial memory
tbi
url https://ijbms.mums.ac.ir/article_17461_aa211a998b5641288b9f79a275600712.pdf
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