EVALUATION OF RECOMBINANT HUMAN BASIC FIBROBLAST GROWTH-FACTOR (RHBFGF) AS A CEREBROPROTECTIVE AGENT USING HIGH-SPEED MR-IMAGING

The potential cerebroprotective effects of recombinant human basic fib roblast growth factor (rhbFGF) were evaluated in a feline model of acu te cerebral ischemia using high-speed magnetic resonance imaging (MRI) in conjunction with immunohistology. The neuroprotective efficacy of three doses of rhbFGF was evaluated in a unilateral middle cerebral ar tery (MCA) occlusion/reperfusion model. Ten h following a 2 h period o f MCA occlusion in control (vehicle-treated) animals, cerebral perfusi on in the ischemic hemisphere was 58 +/- 17% of the contralateral norm al hemisphere. Corresponding ischemic/normal perfusion ratios in rhbFG F-treated groups were not significantly different: 54 +/- 16% (14 mu g /kg/h dose), 40 +/- 19% (42 mu g/kg/h dose) and 75 +/- 8% (125 mu g/kg /h dose). Triphenyltetrazolium chloride histopathological assessment d emonstrated brain damage in vehicle-treated animals comprising 31 +/- 15% of the hemisphere; in rhbFGF-treated groups injury was not signifi cantly different: 19 +/- 4% (14 mu g/kg/h rhbFGF), 24 +/- 6% (42 mu g/ kg/h rhbFGF) and 16 +/- 10% (125 mu g/kg/h rhbFGF). Immunohistochemica l analysis of brain sections using glial fibrillary acidic protein (GF AP) revealed that in animals that showed marked perfusion deficits thr oughout the entire experiment (regardless of treatment), GFAP staining was elevated contralateral to the occlusion and absent ipsilaterally. While some tendency towards protection is found, particularly at high er doses of rhbFGF, it must be concluded that in the chosen stroke mod el and time interval, the doses used did not significantly improve rep erfusion or confer significant cerebroprotective benefit. Non-invasive high-speed MRI was found to be useful for evaluation of putative cere broprotective agents.