title: Angiogenesis therapy for brain infarction using a slow-releasing drug delivery system for fibroblast growth factor 2.
abstract: Although fibroblast growth factor 2 (FGF2) is a promising agent for treating brain infarction, current methods of FGF2 administration are associated with a short circulating half-life. An FGF2 apatite coating was developed as a slow-releasing drug delivery system (DDS) by forming an FGF2/calcium phosphate composite layer. Hydroxyapatite was coated with high or low doses of FGF2, denoted as FGF-high and FGF-low. This study investigated the efficacy of the coating as angiogenesis therapy for brain infarction. Rats were subjected to permanent occlusion of the middle cerebral artery, an FGF2 apatite-coated implant was inserted, and the rat brains were removed 2 weeks after implantation. Rats in groups treated with FGF-high had significantly smaller areas of brain infarction, particularly in the external capsule and the lateral side of the putamen, and better capillary density than rats in groups treated with non-FGF2 apatite-coated implants. Histologic analysis indicated that the new vessels were larger and had thicker walls in the FGF2 apatite-coated groups than in the non-FGF2 groups. Fluorescence immunohistochemistry of the peri-infarction region showed that FGF2 released from FGF2 apatite-coated implants might have biological activity. Moreover, fluorescence immunohistochemistry showed that released FGF2 influenced microglia cells. This new FGF2 DDS involving an FGF2 apatite coating can prevent infarction of the penumbra through the multipotential effects of FGF2.
authors: Department of Neurosurgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennnoudai 1-1-1, Tsukuba, Ibaraki 305-8575, Japan.
authors: Yoshiro
authors: Y
authors: Ito
authors: Hideo
authors: H
authors: Tsurushima
authors: Masayuki
authors: M
authors: Sato
authors: Atsuo
authors: A
authors: Ito
authors: Ayako
authors: A
authors: Oyane
authors: Yu
authors: Y
authors: Sogo
authors: Akira
authors: A
authors: Matsumura
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage*; D000818:Animals; D001031:Apatites / Q000737:chemistry; D001921:Brain / Q000098:blood supply* / Q000187:drug effects* / Q000473:pathology; D020520:Brain Infarction / Q000188:drug therapy* / Q000473:pathology; D002196:Capillaries / Q000473:pathology; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D043925:Angiogenesis Inducing Agents; D001031:Apatites; D003692:Delayed-Action Preparations; D016222:Fibroblast Growth Factor 2