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.
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.
Bellomo
Maria
M
Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Messina, Italy.
Adamo
Elena Bianca
EB
Deodato
Barbara
B
Catania
Maria Antonietta
MA
Mannucci
Carmen
C
Marini
Herbert
H
Marciano
Maria Concetta
MC
Marini
Rolando
R
Sapienza
Salvatore
S
Giacca
Mauro
M
Caputi
Achille P
AP
Squadrito
Francesco
F
Calapai
Gioacchino
G
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
D042461:Vascular Endothelial Growth Factor A