title: Permeability of injured blood brain barrier for exogenous bFGF and protection mechanism of bFGF in rat brain ischemia.
abstract: The study aims to explore the protection mechanism of exogenous basic fibroblast growth factor (exo-bFGF) in brain ischemia. The first part of experiment was to determine the optimal time window for the permeation of exo-bFGF through damaged blood-brain barrier in rats with permanently occluded middle cerebral arteries. 125I labeled bFGF was administered to the rats through the caudal vein. The level of gamma-rays of 125I-bFGF in the ischemic brain were found to increase at 2 h and a high level was maintained for 14 days. The morphology of the basement membrane of capillaries was observed using anti-blood-brain barrier basement membrane glycoprotein immunohistochemistry. The normal continuous linear or ribbon-like immunostain of the basement membrane became granular at 0.5 h, gradually faint and finally negative. The newly formed capillaries at the edge of the infarct still showed a negative stain after 14 days. The result suggested the optimal time window of exo-bFGF began 2 h after insult. The second part of experiment was to observe the dynamic expression of early growth response protein (Egr-1), endogenous basic fibroblast growth factor (endo-bFGF) and bFGF receptor (bFGFR) using immunohistochemistry after exo-bFGF is administered to brain. Egr-1 was more significantly enhanced in the exo-bFGF-used group than in the control group. Endo-bFGF increased gradually, reaching its peak at 7 days in the control group, while in experiment group, the endo-bFGF expression showed its first peak at 6 h, indicating that exo-bFGF could induce earlier and stronger expression of endo-bFGF. The bFGFR-group presented an early expression, reaching its maximal level at 3 h, and declining at 6 h. There were no difference in expression of bFGFR between the two groups. The infarct areas reduced from 17% to 24% in the different time intervals. The results suggested that in exo-bFGF enhanced Egr-1 protein. Egr-1 in turn might play an important role in up-regulating the expression of endo-bFGF which overlapped with the expression of bFGFR to ensure the combination of ligand and receptor to protect against brain ischemia.
authors.affiliation: Department of Pathology, Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China. jiwmliuying@hotmail.com
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Jin-Biao
authors.initials: JB
authors.lastname: Lu
authors.forename: Zhu-Rong
authors.initials: ZR
authors.lastname: Ye
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D002199:Capillary Permeability / Q000187:drug effects*; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology; D007457:Iodine Radioisotopes; D051381:Rats; D017208:Rats, Wistar
chemical_list: D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D007457:Iodine Radioisotopes; D016222:Fibroblast Growth Factor 2