Article
Preconditioning with intramuscular injection of vascular endothelial growth factor gene (VEGF164) attenuates ischemic brain injury after transient focal cerebral ischemia in rats
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Published: | May 20, 2009 |
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Objective: Vascular growth factor stimulating the angiogenesis was shown to be a potential novel therapeutic approach for the treatment of ischemic vascular disease. The goal of the present study was to examine whether gene delivery of vascular endothelial growth factor (VEGF164) can provide a useful approach to the treatment of brain ischemia after transient middle cerebral artery occlusion (tMCAO).
Methods: Three groups of male rats (n=32) received intramuscular injections with pLEN-VEGF164, pLEN or saline for two times at intervals of seven days. Seven days after the last gene transfer, the rats underwent 45 minutes of tMCAO. Body temperature was maintained at 37.0±0.5°C. Reperfusion was performed by removing the filament and retained for 24 h. Infarct volume was determined using cresyl violet staining; neuronal injury was examined using TUNEL staining.
Results: Five animals passed away due to subarachnoid hemorrhage; two as the result of stroke. 25 brains were analyzed (9 in the gene-transferred group, 10 in the control group and 6 in the saline group). Infarct volume was smaller in the pLEN-VEGF-transduced group compared with the pLEN and saline groups (43% reduction, p<0.05). TUNEL staining showed no significant differences in the three groups.
Conclusions: Intramuscular injection of VEGF164 seven days in advance of tMCAO significantly reduced the ischemic area and therefore provides effective neuroprotection in the animal model. Immunohistochemistry (TUNEL) did not display any significant difference in the three groups, which may be attributed to the short reperfusion time