Attenuation of Cerebral Ischemic Injury in Smad1 Deficient Mice

Stroke results in brain tissue damage from ischemia and oxidative stress. Molecular regulators of the protective versus deleterious cellular responses after cerebral ischemia remain to be identified. Here, we show that deletion of Smad1, a conserved transcription factor that mediates canonical bone...

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Main Authors:	Wong, Jamie K., Chen, Lei, Huang, Yong, Sehba, Fatima A., Friedel, Roland H., Zou, Hongyan
Format:	Online
Language:	English
Published:	Public Library of Science 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552810/

id	pubmed-4552810
recordtype	oai_dc
spelling	pubmed-45528102015-09-10 Attenuation of Cerebral Ischemic Injury in Smad1 Deficient Mice Wong, Jamie K. Chen, Lei Huang, Yong Sehba, Fatima A. Friedel, Roland H. Zou, Hongyan Research Article Stroke results in brain tissue damage from ischemia and oxidative stress. Molecular regulators of the protective versus deleterious cellular responses after cerebral ischemia remain to be identified. Here, we show that deletion of Smad1, a conserved transcription factor that mediates canonical bone morphogenetic protein (BMP) signaling, results in neuroprotection in an ischemia-reperfusion (I/R) stroke model. Uninjured mice with conditional deletion of Smad1 in the CNS (Smad1 cKO) displayed upregulation of the reactive astrocyte marker GFAP and hypertrophic morphological changes in astrocytes compared to littermate controls. Additionally, cultured Smad1 -/- astrocytes exhibited an enhanced antioxidant capacity. When subjected to I/R injury by transient middle cerebral artery occlusion (tMCAO), Smad1 cKO mice showed enhanced neuronal survival and improved neurological recovery at 7 days post-stroke. This neuroprotective phenotype is associated with attenuated reactive astrocytosis and neuroinflammation, along with reductions in oxidative stress, p53 induction, and apoptosis. Our data suggest that Smad1-mediated signaling pathway is involved in stroke pathophysiology and may present a new potential target for stroke therapy. Public Library of Science 2015-08-28 /pmc/articles/PMC4552810/ /pubmed/26317208 http://dx.doi.org/10.1371/journal.pone.0136967 Text en © 2015 Wong et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Wong, Jamie K. Chen, Lei Huang, Yong Sehba, Fatima A. Friedel, Roland H. Zou, Hongyan
spellingShingle	Wong, Jamie K. Chen, Lei Huang, Yong Sehba, Fatima A. Friedel, Roland H. Zou, Hongyan Attenuation of Cerebral Ischemic Injury in Smad1 Deficient Mice
author_facet	Wong, Jamie K. Chen, Lei Huang, Yong Sehba, Fatima A. Friedel, Roland H. Zou, Hongyan
author_sort	Wong, Jamie K.
title	Attenuation of Cerebral Ischemic Injury in Smad1 Deficient Mice
title_short	Attenuation of Cerebral Ischemic Injury in Smad1 Deficient Mice
title_full	Attenuation of Cerebral Ischemic Injury in Smad1 Deficient Mice
title_fullStr	Attenuation of Cerebral Ischemic Injury in Smad1 Deficient Mice
title_full_unstemmed	Attenuation of Cerebral Ischemic Injury in Smad1 Deficient Mice
title_sort	attenuation of cerebral ischemic injury in smad1 deficient mice
description	Stroke results in brain tissue damage from ischemia and oxidative stress. Molecular regulators of the protective versus deleterious cellular responses after cerebral ischemia remain to be identified. Here, we show that deletion of Smad1, a conserved transcription factor that mediates canonical bone morphogenetic protein (BMP) signaling, results in neuroprotection in an ischemia-reperfusion (I/R) stroke model. Uninjured mice with conditional deletion of Smad1 in the CNS (Smad1 cKO) displayed upregulation of the reactive astrocyte marker GFAP and hypertrophic morphological changes in astrocytes compared to littermate controls. Additionally, cultured Smad1 -/- astrocytes exhibited an enhanced antioxidant capacity. When subjected to I/R injury by transient middle cerebral artery occlusion (tMCAO), Smad1 cKO mice showed enhanced neuronal survival and improved neurological recovery at 7 days post-stroke. This neuroprotective phenotype is associated with attenuated reactive astrocytosis and neuroinflammation, along with reductions in oxidative stress, p53 induction, and apoptosis. Our data suggest that Smad1-mediated signaling pathway is involved in stroke pathophysiology and may present a new potential target for stroke therapy.
publisher	Public Library of Science
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552810/
_version_	1613470197116567552

Attenuation of Cerebral Ischemic Injury in Smad1 Deficient Mice

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