title: Attenuation of Cerebral Ischemic Injury in Smad1 Deficient Mice.
abstract: 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.
authors: Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, United States of America.
authors: Jamie K
authors: JK
authors: Wong
authors: Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, United States of America.
authors: Lei
authors: L
authors: Chen
authors: Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, United States of America.
authors: Yong
authors: Y
authors: Huang
authors: Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, United States of America.
authors: Fatima A
authors: FA
authors: Sehba
authors: Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, United States of America; Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, United States of America.
authors: Roland H
authors: RH
authors: Friedel
authors: Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, United States of America; Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, United States of America.
authors: Hongyan
authors: H
authors: Zou
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D051379:Mice; D018384:Oxidative Stress; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction; D051898:Smad1 Protein / Q000172:deficiency*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; D016159:Tumor Suppressor Protein p53; C528900:glial fibrillary astrocytic protein, mouse