Original ArticlesIntravenous Fibroblast Growth Factor Penetrates the Blood-Brain Barrier and Protects Hippocampal Neurons Against Ischemia-Reperfusion Injury
Section snippets
Material and Methods
Animal care procedures were conducted in accordance with the guidelines set by the European Community council directives 86/6091 EEC.
Analysis of Rat Hippocampal Autoradiograms
Our specific experimental approach to the study of the efficiency of the intravenous administration of FGFs to protect brain tissues from the effects of transient ischemia was undertaken on the assumption that these proteins are able to cross the BBB after systemic administration. Therefore, we studied previously if FGFs effectively accumulate in the hippocampus, a region where the effects of transient ischemia are depicted most strikingly. Histological autoradiograms effectively showed
Discussion
This article presents data showing that systemic administration of FGFs protects hippocampal neurons against ischemia/reperfusion injury. Our results also show that an engineered aFGF lacking mitogenic activity affords efficient protection, too. Recognition of FGFs by their cell membrane receptors evokes a cascade of early and late intracellular events 1, 30, 31. It seems that early events are not enough to trigger mitogenesis [30]. Nevertheless, they seem sufficient for sustaining some other
Acknowledgements
This work was supported by CICYT and Fundación Gregorio Marañon- and Fundación Futuro-Boehringer Ingelheim España S.A. agreements. Human recombinant 14C-bFGF used in these studies was provided by Dr. Y. Courtois (Unité de Recherches Gérontologiques, INSERM, Paris), to whom we express our gratitude. We are also grateful to Dr.. I. Saenz de Tejada for criticisms and C. Bourdier for editorial assistance.
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