TRANSFORMING GROWTH-FACTOR-BETA-1 EXHIBITS DELAYED GENE-EXPRESSION FOLLOWING FOCAL CEREBRAL-ISCHEMIA

Transforming growth factor-beta 1 (TGF-beta 1) is a pleiotropic peptide growth factor. The expression of TGF-beta 1 mRNA in the focal ischemic cortex of rats was studied by means of Northern hybridization, A moderately low level of constitutively expressed TGF-beta 1 mRNA was detected following sham-surgery or in the contralateral (nonischemic) cortex. A significant increase of TGF-beta 1 mRNA level in the ischemic cortex was observed at 2 days (3.2-fold increase compared to sham-operated animals, p < 0.01, n = 4) following permanent occlusion of the middle cerebral artery (PMCAO), The elevated TGF-beta 1 mRNA expression was plateaued for up to 15 days (3.6-fold increase, p < 0.01) following PMCAO. This temporal profile for TGF-beta 1 mRNA expression in focal stroke was significantly delayed compared to that of TNF-alpha, IL-1 beta and IL-6 mRNA expressions as demonstrated previously which peaked at 12 h and decreased to almost basal levels by 5 days following PMCAO. Interestingly, the TGF-beta 1 mRNA expression profile was remarkably parallel with that of monocyte/macrophage accumulation in the ischemic cortex, as well as with the increased formation of extracellular matrix in the focal ischemic brain. These data suggest that TGF-beta 1 may play a role in anti-inflammatory process and in tissue remodeling following ischemic brain injury.