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

There has been an increasing interest in recent years in the evaluation of the neuronal and glial responses to ischemic insult. Some cytokines, includ ing transforming growth factor-beta (TGF-beta), that are overexpressed afte r experimental stroke in rodents are thought to be implicated in the neuron al processes that lead to necrosis. Thus, such cytokines could predict tiss ue fate after stroke in humans, although data are currently sparse for gyre ncephalic species. The current study addressed the expression pattern of TG F-beta1 in a nonhuman primate model of middle cerebral artery occlusion. Fo cal permanent ischemia was induced for 1 or 7 days in 6 baboons and the fol lowing investigations were undertaken: cerebral oxygen metabolism (CMRO2) p ositron 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-beta1 to the unde rlying metabolic and histologic state of the threatened cerebral parenchyma . The authors evidenced increased TGF-beta1 mRNA levels (up to 25-fold) in those regions displaying a moderate (20% to 49%) reduction in CMRO2. The cu rrent findings suggest that the greatly enhanced expression of TGF-beta1 in the penumbral zones that surround tissue destined to infarction may repres ent a robust index of potentially salvageable brain. The current investigat ion, in the nonhuman primate, strengthens the authors' hypothesis, derived from rodent models, that TGF-beta1 may be involved in the physiopathology o f human stroke.