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 fibroblast growth factor (rhbFGF) were evaluated in a feline model of acute 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 artery (MCA) occlusion/reperfusion model. Ten h following a 2 h period of MCA occlusion in control (vehicle-treated) animals, cerebral perfusion in the ischemic hemisphere was 58 +/- 17% of the contralateral normal hemisphere. Corresponding ischemic/normal perfusion ratios in rhbFGF-treated groups were not significantly different: 54 +/- 16% (14 micrograms/kg/h dose), 40 +/- 19% (42 micrograms/kg/h dose) and 75 +/- 8% (125 micrograms/kg/h dose). Triphenyltetrazolium chloride histopathological assessment demonstrated brain damage in vehicle-treated animals comprising 31 +/- 15% of the hemisphere; in rhbFGF-treated groups injury was not significantly different: 19 +/- 4% (14 micrograms/kg/h rhbFGF), 24 +/- 6% (42 micrograms/kg/h rhbFGF) and 16 +/- 10% (125 micrograms/kg/h rhbFGF). Immunohistochemical analysis of brain sections using glial fibrillary acidic protein (GFAP) revealed that in animals that showed marked perfusion deficits throughout 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 higher doses of rhbFGF, it must be concluded that in the chosen stroke model and time interval, the doses used did not significantly improve reperfusion or confer significant cerebroprotective benefit. Non-invasive high-speed MRI was found to be useful for evaluation of putative cerebroprotective agents.
Roberts
T P
TP
Department of Radiology, University of California at San Francisco 94143, USA.
Vexler
Z S
ZS
Derugin
N
N
Kozniewska
E
E
Kucharczyk
J
J
Emmett
C J
CJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy*; D002415:Cats; D002540:Cerebral Cortex / Q000187:drug effects*; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data; D011995:Recombination, Genetic; D013997:Time Factors
D016222:Fibroblast Growth Factor 2