Pretreatment with intraventricular basic fibroblast growth factor decreases infarct size following focal cerebral ischemia in rats

Abstract

Basic fibroblast growth factor is a polypeptide with potent multipotential trophic effects on central nervous system cells, including neurons, glia, and endothelial cells. In particular, it promotes the survival of a wide variety of brain neurons in vitro, and protects these neurons against the effects of several neurotoxins, including excitatory amino acids, hypoglycemia, and calcium ionophore. Since lack of substrate delivery, excitatory amino acid toxicity, and calcium entry into cells appear to be important processes in neuronal death after ischemia, we tested the hypothesis that pretreatment with basic fibroblast growth factor limits infarct size in a model of focal cerebral ischemia in vivo. Mature male Long-Evans rats received either continuous intraventricular infusion of basic fibroblast growth factor (1.2 micrograms/day; with or without heparin, added to stabilize the growth factor) or vehicle alone for 3 days before focal ischemic infarcts were made in the right lateral cerebral cortex by permanent distal middle cerebral artery occlusion and temporary (45-minute) bilateral carotid occlusion. Intraoperative measurements of core temperature, arterial blood pressure and blood gases, blood glucose concentration, and hematocrit, and postoperative measurements of temperature revealed no differences among vehicle- versus basic fibroblast growth factor-treated animals. Twenty-four hours later, animals were killed, brains were removed and stained to visualize cortical infarcts, and infarct volume was determined by image analysis. Overall, we found a 25% reduction in infarct volume in basic fibroblast growth factor- (N = 25) versus vehicle-treated (N = 23) animals (p < 0.01). This reduction was not enhanced by the addition of heparin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoviral gene transfer of basic fibroblast growth factor promotes angiogenesis in rat brain

“…18,36 Some investigators also reported that intraventricular administration of a relatively large amount of bFGF protein showed some neurotrophic effects in a rat ischemic model. 46,47 Neuronal rescue experiments using these viral vectors are currently in progress with an ischemic rat model.…”

Delayed Treatment with Intravenous Basic Fibroblast Growth Factor Reduces Infarct Size following Permanent Focal Cerebral Ischemia in Rats

“…Brains were then sectioned into 2-mm coronal slices, which were incubated in 2% 2,3,5-triphenyltetrazolium hydrochlo ride (TTC) for 30 min, and fixed in 10% buffered forma lin. This procedure stains viable tissue red; infarcted tis sue remains unstained (Koketsu et a!., 1994). After 48 h, sections were photographed (Zeiss microscope, 0.8x magnification), and infarct size in each of five slices was determined using a computer-interfaced digitizer (Signa Scan V 3.10; Jandel Scientific, Costa Madera, CA, U.S.A.; and Numonics 2200, Numonics, Montgomer yville, PA, U.S.A.; slices 1-5-bregma coordinates +2.4, +0.4, -1.6, -3.6, and -5.4, respectively).…”

Intracisternal Basic Fibroblast Growth Factor (bFGF) Enhances Behavioral Recovery following Focal Cerebral Infarction in the Rat

“…Endogenous bFGF expression is upregulated in tissue surround ing focal brain wounds or infarcts, and exogenous application of bFGF reduces the degree of cell death and stimulates neuronal sprouting in several models of brain injury or ischemia (Berlove and Finklestein, 1993;Finklestein, 1995). In particular, in previous studies, we showed that bFGF, admin istered intraventricularly or intravenously before or just after ischemia, reduced infarct volume and neu rological deficits in models of focal cerebral isch emia in mature rats (Koketsu et al, 1994;Fisher et al , 1995). The mechanisms of infarct reduction may include direct protective effects on cells at the bor ders ("penumbra") of focal infarcts and/or effects on cerebrovascular tone and cerebral blood flow.…”