Permeability of injured blood brain barrier for exogenous bFGF and protection mechanism of bFGF in rat brain ischemia.
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.
Liu
Ying
Y
Department of Pathology, Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China. jiwmliuying@hotmail.com
Lu
Jin-Biao
JB
Ye
Zhu-Rong
ZR
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
D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D007457:Iodine Radioisotopes; D016222:Fibroblast Growth Factor 2