Transforming growth factor-β

A neuroprotective factor in cerebral ischemia

Research output: Contribution to journalReview article

95 Citations (Scopus)

Abstract

Transforming growth factor-β (TGF-β) 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-β1 levels are enhanced in the brain following cerebral ischemia. As evidence that such an upregulation is beneficial, agonist studies have demonstrated that TGF-β1 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-β1 has a neuroprotective role in cerebral ischemia. Recent work with adenoviral-mediated overexpression of TGF-β1 in vivo in mice has further implicated a neuroprotective role for TGF-β1 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-β1 in neurons from a variety of species, including rats, mice, chicks, and humans. Of significant interest, TGF-β1 was shown to be protective against a wide variety of death-inducing agents/insults, including hypoxia/ischemia, glutamate excitotoxicity, β-amyloid, oxidative damage, and human immunodeficiency virus. The mechanism of TGF-β1-mediated neuroprotection remains to be resolved, but early evidence suggests that TGF-β1 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-β1 is an important neuroprotective factor that can reduce damage from a wide-array of death-inducing agents/insults in vitro, as well as exert protection of the brain during cerebral ischemia.

Original languageEnglish (US)
Pages (from-to)13-22
Number of pages10
JournalCell Biochemistry and Biophysics
Volume39
Issue number1
DOIs
StatePublished - Aug 1 2003

Fingerprint

Transforming Growth Factors
Brain Ischemia
Cell Death
Cell death
Middle Cerebral Artery Infarction
Brain
bcl-Associated Death Protein
Neurology
Viruses
Amyloid
Neurons
Rats
Glutamic Acid
Cell Survival
Up-Regulation
Ischemia
Central Nervous System
Cells
HIV

Keywords

  • Brain
  • Central nervous system
  • Cerebral cortex
  • Excitotoxicity
  • Hippocampus
  • Ischemia
  • Neuroprotection
  • Stroke
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Biophysics

Cite this

Transforming growth factor-β : A neuroprotective factor in cerebral ischemia. / Dhandapani, Krishnan Michael; Brann, Darrell W.

In: Cell Biochemistry and Biophysics, Vol. 39, No. 1, 01.08.2003, p. 13-22.

Research output: Contribution to journalReview article

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