Delayed treatment with intravenous basic fibroblast growth factor reduces infarct size following permanent focal cerebral ischemia in rats
Department of Neurology
Animals; Autoradiography; Blood-Brain Barrier; Brain; Brain Ischemia; Cerebral Infarction; Fibroblast Growth Factor 2; Injections, Intravenous; Male; Precipitin Tests; Rats; Rats, Sprague-Dawley; Time Factors
Nervous System Diseases | Neurology
Basic fibroblast growth factor (bFGF) is a polypeptide that supports the survival of brain cells (including neurons, glia, and endothelia) and protects neurons against a number of toxins and insults in vitro. This factor is also a potent dilator of cerebral pial arterioles in vivo. In previous studies, we found that intraventricularly administered bFGF reduced infarct volume in a model of focal cerebral ischemia in rats. In the current study, bFGF (45 micrograms/kg/h) in vehicle, or vehicle alone, was infused intravenously for 3 h, beginning at 30 min after permanent middle cerebral artery occlusion by intraluminal suture in mature Sprague-Dawley rats. After 24 h, neurological deficit (as assessed by a 0- to 5-point scale, with 5 = most severe) was 2.6 +/- 1.0 in vehicle-treated and 1.5 +/- 1.3 in bFGF-treated rats (mean +/- SD; N = 12 vs. 11; p = 0.009). Infarct volume was 297 +/- 65 mm3 in vehicle- and 143 +/- 135 mm3 in bFGF-treated animals (p = 0.002). During infusion, there was a modest decrease in mean arterial blood pressure but no changes in arterial blood gases or core or brain temperature in bFGF-treated rats. Autoradiography following intravenous administration of 111In-labeled bFGF showed that labeled bFGF crossed the damaged blood-brain barrier to enter the ischemic (but not the nonischemic) hemisphere. Whether the infarct-reducing effects of bFGF depend on intraparenchymal or intravascular mechanisms requires further study.
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Citation: J Cereb Blood Flow Metab. 1995 Nov;15(6):953-9.
Fisher, Marc; Meadows, Mary-Ellen; Do, Tuyen; Weise, Jens; Trubetskoy, Vladimir; Charette, Marc; and Finklestein, Seth P., "Delayed treatment with intravenous basic fibroblast growth factor reduces infarct size following permanent focal cerebral ischemia in rats" (1995). Neurology Publications and Presentations. Paper 102.