Adenoviral vector-mediated transduction of VEGF improves neural functional recovery after hypoxia-ischemic brain damage in neonatal rats.
Previous studies have showed that vascular endothelial growth factor (VEGF) displayed neurotrophic and neuroprotective activities. To examine whether target delivery of VEGF gene directly into brain may prevent ischemic brain damage, the VEGF expression adenoviral vectors, AVHP.VEGF-with 476bp of the human preproendothelin-1 (ppET-1) promoter and 35bp of the hypoxia-reponse element (HRE) driving VEGF expression and CMV.VEGF were transferred into hypoxic-induced ischemic (HI) rat brains. Seven-day-old rats that were underwent left carotid ligation followed by 2h of hypoxic stress (8% O(2) at 37 degrees C) were received VEGF adenoviral vectors or buffer (PBS) injection 3 days after HI. The body weight, VEGF expression, neuronal apoptosis, cerebral morphology and brain functional assays were performed between 7 and 28 days after HI. There were remarkable increases in the body weight and VEGF protein expression, and decrease in the number of TUNEL-positive cells in the VEGF vector groups as compared with PBS group. The VEGF vector groups also had better brain functional performs than PBS group. The better performs by the animals that received VEGF vectors may be directly linked to the inhibitory effect of VEGF on neuronal apoptosis because the animals had less neural loss in the cortex and hippocampal CA1 region as compared with PBS group. Overall, these results indicated that over-expression of VEGF in the brain exerted a neuroprotective effect and promoted neural functional recovery in neonatal rats after hypoxic-ischemic brain damage, suggesting that in vivo target VEGF gene transfer to brain may be a promising approch for the treatment of such implications.
Zheng
Xiang-Rong
XR
Department of Pediatrics, XiangYa Hospital, Central South University, Changsha 410008, Hunan, China. zhengxiangrong@sohu.com
Zhang
Shan-Shan
SS
Yang
Yu-Jia
YJ
Yin
Fei
F
Wang
Xia
X
Zhong
Le
L
Yu
Xiao-He
XH
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D019332:Endothelin-1 / Q000235:genetics; D005822:Genetic Vectors; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009474:Neurons / Q000502:physiology; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000235:genetics / Q000502:physiology; D013997:Time Factors; D014161:Transduction, Genetic / Q000379:methods*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism*
D019332:Endothelin-1; D042461:Vascular Endothelial Growth Factor A