Experimental studies on the different route of gene transfer of rAAV-VEGF_(165)into ischemic rat brain to affect the angiogenesis in the ischemic penumbra in rats

Objective To investigate the effect of recombinant adeno-associated virus mediated vascular en-dothelial growth factor 165 gene (rAAV-VEGF165) on angiogenesis in the ischemic penumbra in rats by cere-brospinal fluid (CSF) or intravenous route. Methods After establishing a rat model of permanent middle cerebral artery occlusion (MACO) by nylon suture embolization and cerclage,the rAAV-VEGF165gene was injected through CSF or intravenous in 24 hours. On the 7th and 14th day,the rats were killed,microvessel density was assessed with CD34 immunohistochemistry. Results The density of CD31-IR-positive cell (under high power field, ×200) in the cerebral ischemic penumbra of each group at the 7th day was 92. 73±5. 18 in CSF group, 77. 40±5. 43 in intravenous group,46. 50±5. 33 in MCAO group and 13. 90±1. 49 in sham-operation group respectively(P0. 05)s and at the 14th day was 104. 05±4. 30 in CSF group,89. 88 ± 5. 77 in intravenous group,65. 33 ± 2. 31 in MCAO group and 13. 08±1. 90 in sham-operation group respectively(P0. 05). Conclusion The rAAV-VEGF165 can be transfected into the cerebral ischemic tissue through both CSF route and intravenous route to express VEGF,which can promote the formation of new vessels and protect neurocytes in cerebral ischemic disease.