title: Enhancement of expression of vascular endothelial growth factor after adeno-associated virus gene transfer is associated with improvement of brain ischemia injury in the gerbil.
abstract: Angiogenesis induced by growth factors may represent a rational therapy for patients with stroke. Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis and VEGF expression is enhanced in the post-ischemic brain. VEGF induced by brain hypoxia can lead to the growth of new vessels and may represent a natural protective mechanism improving survival after stroke. In the light of these findings we investigated changes of VEGF expression in different brain regions after intracerebroventricular injection of adeno-associated virus transferring gene for VEGF (rAAV-VEGF) in the gerbil, and after transient brain ischemic injury, we studied the effects of rAAV-VEGF injection on survival, brain edema, delayed neuronal death in the CA1 area and learning ability. Treatment with rAAV-VEGF 6 days or 12 days before ischemia significantly improves survival, brain edema and CA1 delayed neuronal death and post-ischemic learning evaluated by passive avoidance test. Animals treated with rAAV-VEGF showed in the thalamus and the cortex, a significant positive immunostaining for VEGF similar to those subjected to brain ischemia and not treated with rAAV-VEGF. These data represent a further contribution to a possible employment of gene therapy by using rAAV-VEGF in brain ischemia and indicate that thalamus and cortex may be targets for neuroprotective effects of VEGF.
authors.affiliation: Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Messina, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Bellomo
authors.forename: Elena Bianca
authors.initials: EB
authors.lastname: Adamo
authors.forename: Barbara
authors.initials: B
authors.lastname: Deodato
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Catania
authors.forename: Carmen
authors.initials: C
authors.lastname: Mannucci
authors.forename: Herbert
authors.initials: H
authors.lastname: Marini
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Marciano
authors.forename: Rolando
authors.initials: R
authors.lastname: Marini
authors.forename: Salvatore
authors.initials: S
authors.lastname: Sapienza
authors.forename: Mauro
authors.initials: M
authors.lastname: Giacca
authors.forename: Achille P
authors.initials: AP
authors.lastname: Caputi
authors.forename: Francesco
authors.initials: F
authors.lastname: Squadrito
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Calapai
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D000229:Dependovirus / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D005849:Gerbillinae; D002546:Ischemic Attack, Transient / Q000150:complications / Q000473:pathology / Q000628:therapy*; D008297:Male; D013788:Thalamus / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D042461:Vascular Endothelial Growth Factor A