Upregulation of VEGF-A using Engineered Zinc Finger Protein Gene Therapy Increases Cell Survival After Lateral Fluid Percussion Injury in Rats

Vascular endothelial growth factor (VEGF) may play a role in neuroprotection after traumatic brain injury (TBI) in addition to being a regulator of angiogenesis. Gene therapy using an adenovirus carrying an engineered zinc-finger protein (Adv-ZFP) and transcription factor construct targeted to the VEGF gene, has been shown to upregulate genomic expression of VEGF-A isoforms in skeletal muscle. Our objective was to use this gene therapy to explore cell survival in TBI. Rats were subjected to a unilateral fluid percussion injury (FPI) in the cortex. Groups consisted of control, injured and injured-treated animals. Adv-ZFP-VEGF was injected into the cortex and hippocampus. Engineered ZFP-VEGF increases VEGF-A protein levels and correlates with increased CA2 hippocampal cell survival and reduction in apoptotic cell death following TBI. NF200 expression in TBI+VEGF animals was comparable to levels in naive animals. This study suggests a therapeutic strategy to treat delayed cell death in a model of TBI.MAS