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Progesterone attenuates neurological deficits and exerts a protective effect on damaged axons via the PI3K/AKT/mTOR-dependent pathway in a mouse model of intracerebral hemorrhage

Intracerebral hemorrhage (ICH) is a devastating event with high disability and fatality rates. However, there is a lack of effective treatments for this condition. We aimed to investigate the neuroprotective and axonal regenerative effects of progesterone after ICH. For this purpose, an ICH model wa...

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Autores principales: Liu, Chang, Gao, Weina, Zhao, Long, Cao, Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9004566/
https://www.ncbi.nlm.nih.gov/pubmed/35305084
http://dx.doi.org/10.18632/aging.203954
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author Liu, Chang
Gao, Weina
Zhao, Long
Cao, Yi
author_facet Liu, Chang
Gao, Weina
Zhao, Long
Cao, Yi
author_sort Liu, Chang
collection PubMed
description Intracerebral hemorrhage (ICH) is a devastating event with high disability and fatality rates. However, there is a lack of effective treatments for this condition. We aimed to investigate the neuroprotective and axonal regenerative effects of progesterone after ICH. For this purpose, an ICH model was established in adult mice by injecting type VII collagenase into the striatum; the mice were then treated with progesterone (8 mg/kg). Hematoma absorption, neurological scores, and brain water content were evaluated on days one, three, and seven after the ICH. The effect of progesterone on inflammation and axonal regeneration was examined on day three after the ICH using western blotting, immunohistochemistry, immunofluorescence, as well as hematoxylin-eosin, Nissl, and Luxol fast blue staining. In addition, we combined progesterone with the phosphoinositide 3-kinase/serine/threonine-specific protein kinase (PI3K/AKT) inhibitor, LY294002, to explore its potential neuroprotective mechanisms. Administration of progesterone attenuated the neurological deficits and expression of inflammatory cytokines and promoted axonal regeneration after ICH, this effect was blocked by LY294002. Collectively, these results suggest that progesterone could reduce axonal damage and produced partial neuroprotective effects after ICH through the PI3K/AKT/mTOR pathway, providing a new therapeutic target and basis for the treatment of ICH.
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spelling pubmed-90045662022-04-13 Progesterone attenuates neurological deficits and exerts a protective effect on damaged axons via the PI3K/AKT/mTOR-dependent pathway in a mouse model of intracerebral hemorrhage Liu, Chang Gao, Weina Zhao, Long Cao, Yi Aging (Albany NY) Research Paper Intracerebral hemorrhage (ICH) is a devastating event with high disability and fatality rates. However, there is a lack of effective treatments for this condition. We aimed to investigate the neuroprotective and axonal regenerative effects of progesterone after ICH. For this purpose, an ICH model was established in adult mice by injecting type VII collagenase into the striatum; the mice were then treated with progesterone (8 mg/kg). Hematoma absorption, neurological scores, and brain water content were evaluated on days one, three, and seven after the ICH. The effect of progesterone on inflammation and axonal regeneration was examined on day three after the ICH using western blotting, immunohistochemistry, immunofluorescence, as well as hematoxylin-eosin, Nissl, and Luxol fast blue staining. In addition, we combined progesterone with the phosphoinositide 3-kinase/serine/threonine-specific protein kinase (PI3K/AKT) inhibitor, LY294002, to explore its potential neuroprotective mechanisms. Administration of progesterone attenuated the neurological deficits and expression of inflammatory cytokines and promoted axonal regeneration after ICH, this effect was blocked by LY294002. Collectively, these results suggest that progesterone could reduce axonal damage and produced partial neuroprotective effects after ICH through the PI3K/AKT/mTOR pathway, providing a new therapeutic target and basis for the treatment of ICH. Impact Journals 2022-03-19 /pmc/articles/PMC9004566/ /pubmed/35305084 http://dx.doi.org/10.18632/aging.203954 Text en Copyright: © 2022 Liu et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Liu, Chang
Gao, Weina
Zhao, Long
Cao, Yi
Progesterone attenuates neurological deficits and exerts a protective effect on damaged axons via the PI3K/AKT/mTOR-dependent pathway in a mouse model of intracerebral hemorrhage
title Progesterone attenuates neurological deficits and exerts a protective effect on damaged axons via the PI3K/AKT/mTOR-dependent pathway in a mouse model of intracerebral hemorrhage
title_full Progesterone attenuates neurological deficits and exerts a protective effect on damaged axons via the PI3K/AKT/mTOR-dependent pathway in a mouse model of intracerebral hemorrhage
title_fullStr Progesterone attenuates neurological deficits and exerts a protective effect on damaged axons via the PI3K/AKT/mTOR-dependent pathway in a mouse model of intracerebral hemorrhage
title_full_unstemmed Progesterone attenuates neurological deficits and exerts a protective effect on damaged axons via the PI3K/AKT/mTOR-dependent pathway in a mouse model of intracerebral hemorrhage
title_short Progesterone attenuates neurological deficits and exerts a protective effect on damaged axons via the PI3K/AKT/mTOR-dependent pathway in a mouse model of intracerebral hemorrhage
title_sort progesterone attenuates neurological deficits and exerts a protective effect on damaged axons via the pi3k/akt/mtor-dependent pathway in a mouse model of intracerebral hemorrhage
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9004566/
https://www.ncbi.nlm.nih.gov/pubmed/35305084
http://dx.doi.org/10.18632/aging.203954
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