Intravenous fibroblast growth factor penetrates the blood-brain barrier and protects hippocampal neurons against ischemia-reperfusion injury

BACKGROUND Fibroblast growth factors (FGFs) play a role in neuronal survival after brain ischemia when administered intracerebrally. However, the clinical problems that chronic intracerebral infusion of FGFs involves may restrict its use. The purpose of this study was to analyze if FGFs administered intravenously might afford neuroprotection against transient brain ischemia in the light of new published data that suggest that these polypeptides cross the blood brain-barrier (BBB). METHODS The efficacy of acidic fibroblast growth factor (aFGF) treatment was analyzed in a gerbil model of 5 min forebrain ischemia followed by 7 days of reperfusion. Native and nonmitogenic aFGF was injected in gerbils as a bolus through a jugular vein at the onset of reperfusion. Control animals received in the same manner vehicle solution alone. Seven days later, neuroprotection was evaluated histologically. Penetration of the FGF across the BBB was assessed by autoradiographic studies in rats. For that purpose, we injected through the jugular vein 0.1 mu g of uniformly labeled native C-14-basic fibroblast growth factor (bFGF), 0.1 mu g of heat-denatured C-14-bFGF, or a coinjection of C-14-bFGF with a 900-fold excess of unlabeled bFGF. Two hours later, animals were killed for morphological studies. RESULTS We report that a venous injection of either native or nonmitogenic form of aFGF after 5 min forebrain ischemia in the gerbil significantly reduced the occurrence of delayed neuronal death (DND) in the CA1 sector of the hippocampus. We also confirmed that blood-borne C-14-bFGF accumulates in CA1 pyramidal neurons. (C) 1998 by Elsevier Science Inc.