Increased expression of transforming growth factor-β after cerebral ischemia in the baboon: An endogenous marker of neuronal stress?

Carine Ali, Fabian Docagne, Olivier Nicole, Sylvain Lesné, Jér̂me Toutain, Alan Young, Laurent Chazalviel, Didier Divoux, Martial Caly, Philippe Cabal, Jean Michel Derlon, Eric T. Mackenzie, Alain Buisson, Denis Vivien

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

There has been an increasing interest in recent years in the evaluation of the neuronal and glial responses to ischemic insult. Some cytokines, including transforming growth factor-β (TGF-β), that are overexpressed after experimental stroke in rodents are thought to be implicated in the neuronal processes that lead to necrosis. Thus, such cytokines could predict tissue fate after stroke in humans, although data are currently sparse for gyrencephalic species. The current study addressed the expression pattern of TGF-β1 in a nonhuman primate model of middle cerebral artery occlusion. Focal permanent ischemia was induced for 1 or 7 days in 6 baboons and the following investigations were undertaken: cerebral oxygen metabolism (CMRO2) positron emission tomography studies, magnetic resonance imaging, postmortem histology, and reverse transcription-polymerase chain reaction. The aim of the current study was to correlate the expression of TGF-β1 to the underlying metabolic and histologic state of the threatened cerebral parenchyma. The authors evidenced increased TGF-β1 mRNA levels (up to 25-fold) in those regions displaying a moderate (20% to 49%) reduction in CMRO2. The current findings suggest that the greatly enhanced expression of TGF-β1 in the penumbral zones that surround tissue destined to infarction may represent a robust index of potentially salvageable brain. The current investigation, in the nonhuman primate, strengthens the authors' hypothesis, derived from rodent models, that TGF-β1 may be involved in the physiopathology of human stroke.

Original languageEnglish (US)
Pages (from-to)820-827
Number of pages8
JournalJournal of Cerebral Blood Flow and Metabolism
Volume21
Issue number7
DOIs
StatePublished - 2001

Keywords

  • Baboon
  • Focal cerebral ischemia
  • PET
  • Transforming growth factor-β

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