title: Transforming growth factor-beta: a neuroprotective factor in cerebral ischemia.
abstract: Transforming growth factor-beta (TGF-beta) has diverse and multiple roles throughout the body. This review focuses on the evidence supporting its functions in the central nervous system, with a particular emphasis on its purported role in cerebral ischemia. Numerous studies have documented that TGF-beta1 levels are enhanced in the brain following cerebral ischemia. As evidence that such an upregulation is beneficial, agonist studies have demonstrated that TGF-beta1 reduces neuronal cell death and infarct size following middle cerebral artery occlusion (MCAO), while conversely, antagonist studies have shown increased neuronal cell death and infarct size after MCAO. These studies suggest that TGF-beta1 has a neuroprotective role in cerebral ischemia. Recent work with adenoviral- mediated overexpression of TGF-beta1 in vivo in mice has further implicated a neuroprotective role for TGF-beta1 in cerebral ischemia, as evidenced by a reduction in neuronal cell death, infarct size, and neurological outcome. Additionally, numerous in vitro studies have documented the neuroprotective ability of TGF-beta1 in neurons from a variety of species, including rats, mice, chicks, and humans. Of significant interest, TGF-beta1 was shown to be protective against a wide variety of death-inducing agents/insults, including hypoxia/ischemia, glutamate excitotoxicity, beta-amyloid, oxidative damage, and human immunodeficiency virus. The mechanism of TGF-beta1-mediated neuroprotection remains to be resolved, but early evidence suggests that TGF-beta1 regulates the expression and ratio of apoptotic (Bad) and antiapoptotic proteins (Bcl-2, Bcl-x1), creating an environment favorable for cell survival of death-inducing insults. Taken as a whole, these results suggest that TGF-beta1 is an important neuroprotective factor that can reduce damage from a widearray of death-inducing agents/insults in vitro, as well as exert protection of the brain during cerebral ischemia.
authors.affiliation: Institute of Molecular Medicine and Genetics, Department of Neurology, Program in Neurobiology, School of Medicine, Medical College of Georgia, Augusta, GA 30912, USA.
authors.forename: Krishnan M
authors.initials: KM
authors.lastname: Dhandapani
authors.forename: Darrell W
authors.initials: DW
authors.lastname: Brann
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism*; D015398:Signal Transduction; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; D016212:Transforming Growth Factor beta; D020928:Mitogen-Activated Protein Kinases