TGF-BETA-1 POSTTREATMENT IN A RABBIT MODEL OF CEREBRAL-ISCHEMIA

Transforming growth factor-beta 1 (TGF-beta 1), suggested in some stud ies to suppress astrocyte and neutrophil function, has also reduced is chaemic brain injury when administered immediately prior to clot embol ization in models of thromboembolic stroke. The effect of TGF-beta 1 a s a post-treatment paradigm was investigated in a rabbit model of thro mboembolic stroke. Following clot embolization, regional cerebral bloo d flow fell to < 10 cc 100g(-1) min(-1) in all animals. TGF-beta 1 (10 mu g) or vehicle (n = 5 each group) was infused via the contralateral carotid artery. TGF-beta 1 administration resulted in a rapid and sel ective reduction in the peripheral neutrophil count as compared to a s ignificant (p < 0.05) increase in control values (2336 +/- 817 vs 4320 +/- 928 neutrophils mm(3), mean +/- SEM). Neutrophil aggregation was increased within 30 min of TGF-beta 1 infusion when compared to contro l (2.07 +/- 0.70 vs 1.09 +/- 0.17 ohms, p < 0.05); neutrophil chemilum inescence, an index of the oxygen respiratory burst was not significan tly affected by TGF-beta 1 administration. No difference in platelet c ounts or aggregation was noted. There nas no significant difference be tween the two groups regarding brain infarct size (47.5 +/- 10.9 vs 56 .5 +/- 10.4, n = 4, TGF-beta vs control, mean +/- SEM), intracranial p ressure, or brain excitatory amino acid levels (aspartate and glutamat e) within ischaemic regions. It is concluded from the present study th at 1. infusion of TGF-beta 1 as a post-treatment paradigm affords only a modest reduction in ischaemic brain injury in this rabbit model of thromboembolic stroke; 2. TGF-beta 1 functions as a pure chemo-attract ant as determined by both the reduction of peripheral neutrophil count and an associated increased aggregation response without evidence of concomitant activation, the latter examined by luminol-dependent chemi luminescence. Although a small increase in neutrophil accumulation was noted in ischaemic regions of the group receiving TGF-beta 1 (1.87 vs 1.61 x 10(7) neutrophils g(-1) tissue), further studies are necessary to define the site(s) and significance of neutrophil sequestration in ischaemic tissues following TGF-beta 1 administration.