TRANSFORMING GROWTH-FACTOR-BETA-1 REDUCES INFARCT SIZE AFTER EXPERIMENTAL CEREBRAL-ISCHEMIA IN A RABBIT MODEL

Background and Purpose: The aim of this study was to examine the effect of transforming growth factor-beta1, a cytokine shown to amelioriate cardiac ischemia, in a rabbit model of thromboembolic stroke. Methods: An autologous clot embolus was introduced intracranially through the right internal carotid artery in 21 New Zealand White rabbits, with seven in each group receiving either vehicle control (albumin) or 10 or 50 mug transforming growth factor-beta1 administered as an intracarotid bolus immediately before autologous clot embolization. Multiple physiological parameters were monitored, including regional cerebral blood flow, arterial blood gases, hematocrit, glucose, core temperature, and mean arterial pressure. The brain was harvested 4 hours after embolization, and infarct size was determined planimetrically as a percentage of the entire hemisphere. Results: Brain infarct size was reduced in both the 10-mug (16.7+/-4.0% [mean +/- SEM], p < 0.05) and 50-mug (21.7+/-4.5%) transforming growth factor-beta1-treated groups when compared with the control group (31.9+/-6.6%). Regional cerebral blood flow did not show any significant intergroup or intragroup variation over time, although the 10-mug transforming growth factor-beta1 group experienced a greater return of cerebral blood flow in the first 2 hours after embolization. Conclusions: Transforming growth factor-beta1 reduced brain infarct size in a rabbit model of thromboembolic stroke. This effect was not related to a direct effect on blood flow. Studies are ongoing to determine the mechanism by which transforming growth factor-beta1 salvages ischemic brain.