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, including transforming growth factor-beta (TGF-beta), 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-beta1 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-beta1 to the underlying 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 current findings suggest that the greatly enhanced expression of TGF-beta1 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-beta1 may be involved in the physiopathology of human stroke.
Ali
C
C
Université de Caen, UMR CNRS 6551, Cyclotron Biomédical, Caen, France.
Docagne
F
F
Nicole
O
O
Lesné
S
S
Toutain
J
J
Young
A
A
Chazalviel
L
L
Divoux
D
D
Caly
M
M
Cabal
P
P
Derlon
J M
JM
MacKenzie
E T
ET
Buisson
A
A
Vivien
D
D
D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D008279:Magnetic Resonance Imaging; D008297:Male; D020768:Middle Cerebral Artery / Q000601:surgery; D009474:Neurons / Q000502:physiology*; D010101:Oxygen Consumption; D010215:Papio; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014055:Tomography, Emission-Computed; D016212:Transforming Growth Factor beta / Q000235:genetics*
D015415:Biomarkers; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta