Article
Preconditioning with intramuscular injection of VEGF in the rat double subarachnoid hemorrhage model: effects on cerebral vasospasm and neoangiogenesis
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Published: | April 28, 2011 |
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Objective: endothelial growth factor (VEGF) stimulating 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 VEGF164 can provide a useful approach in the treatment of vasospasm-induced ischemic lesions after experimental subarachnoid hemorrhage (SAH).
Methods: Four groups of male rats (n=80) received intramuscular injections with a plasmid containing VEGF164, VEGF-free plasmid or saline three times at 7-day intervals. Seven days after the last gene transfer, vasospasm was induced by double blood injection into the cisterna magna. Vasospasm was analyzed 5 days later by means of digital subtraction angiography investigating large vessels (macroperfusion) and small vessels (microperfusion). Morphological examinations of brain parenchyma were performed using hematoxylin and eosin (HE) staining and immunohistochemical staining of VEGF and CD31.
Results: A total of 44 brains were successfully analyzed (20 in the gene-transferred group, 14 in the control group, 8 in the saline group and 4 in the saline group without SAH). Significant vasospasm (macro- and microperfusion) was induced in all hemorrhage groups compared to the sham-operated group (p<0.05). No significant difference in macroperfusion was detected in the VEGF164-treated group compared to other SAH groups. Analyzing microperfusion and results of HE and CD31 staining a trend to an activated neoangiogenesis with reduced ischemic lesions was documented.
Conclusions: The present study demonstrates reduced vasospasm with acceleration of microperfusion and reduced ischemic lesions in animals treated with VEGF injection prior to induced SAH.