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Richard Garcia
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Time window of fibroblast growth factor-18-mediated neuroprotection after occlusion of the middle cerebral artery in rats.
To assess the time window for fibroblast growth factor-18 (FGF18)-mediated neuroprotection, FGF18 was administered by intravenous infusion at various times after transient occlusion of the middle cerebral artery (MCAO) in rats. Vehicle or FGF18 (100 microg x kg(-1) x h(-1)) was infused at 0.25, 0.5, 1.0, 2.0, 4.0, or 8.0 hours after MCAO with infarct volumes and behavioral deficits measured at 24.0 hours after MCAO. A separate group of animals received the infusions 24 hours after MCAO with endpoints measured at 48 hours after MCAO. Infusion of FGF18 reduced infarct volumes and improved scores in tests of reference and working memory, motor ability, and exploratory behavior. FGF18 was most efficacious when infused within 2 hours after MCAO. Significant reductions in infarct volumes and reductions in deficits of reference memory and motor activity were also observed with FGF18 infused 24 hours after MCAO. Measurements taken at infusion times before 2 hours after MCAO showed that regional cerebral blood flow was increased by FGF18. Administration of vehicle or FGF18 had no significant effect on mean arterial blood pressure, heart rate, brain temperature, blood pH, Pco2, or Po2. These results demonstrate that FGF18 is an effective neuroprotective agent when administered early after transient MCAO in rats. Efficacy observed with infusions at later times suggests an expanded time window for FGF18-mediated neuroprotection.
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Fibroblast growth factor-18 reduced infarct volumes and behavioral deficits after transient occlusion of the middle cerebral artery in rats.
BACKGROUND AND PURPOSE: Fibroblast growth factor 18 (FGF18) is expressed in rodent brain and is a trophic factor for neuron-derived cells in culture. The purpose of the present study was to evaluate whether FGF18 was neuroprotective in a rat model of cerebral ischemia and to compare the results with those obtained with FGF2. METHODS: Cerebral ischemia was produced in rats by a transient 2-hour occlusion of the middle cerebral artery (MCAo) with an intraluminal filament followed by 22-hour reperfusion. Starting 15 minutes after MCAo, FGF18 or FGF2 was administered by a 3-hour intravenous infusion. Infarct volumes and behavioral deficits were measured 24 hours after MCAo. RESULTS: Infusion of FGF18 produced dose-dependent reductions in infarct volumes and improvements in tests of reference and working memory, motor ability, and exploratory behavior. FGF18 was more efficacious than FGF2 on virtually all measures examined. The reductions in infarct volume and behavioral deficit were associated with FGF-mediated increases in regional cerebral blood flow. CONCLUSIONS: These results demonstrate that FGF18 is an effective neuroprotective agent in a rat model of transient MCAo.
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