Adenovirus-mediated VEGF165 gene transfer has neuroprotective effects in neonatal rats following hypoxic-ischemic brain damage / 中国当代儿科杂志
Chinese Journal of Contemporary Pediatrics
; (12): 737-742, 2008.
Artigo
em Chinês
| WPRIM (Pacífico Ocidental)
| ID: wpr-317343
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the protective effects of adenovirus-mediated vascular endothelial growth factor (Ad-VEGF)165 gene transfer against hypoxic-ischemic brain damage (HIBD) in neonatal rats.</p><p><b>METHODS</b>Ad-VEGF recombinant adenovirus was constructed by bacterial homologous recombination technology. Seven-day-old Sprague-Dawley rats were randomly assigned to 4 groups sham-operated (n=20), HIBD (n=25), buffer-treated (n=20), and Ad-VEGF-treated (n=25). The HIBD model was prepared by permanent occlusion of left common carotid artery, followed by exposure to 8% oxygen for 2 hrs. In the Ad-VEGF-treated and the Buffer-treated groups, 2 microL recombinant adenovirus suspension or buffer was injected into the left sensorimotor cortex of the rat brain 3 days after HIBD. Seven days after transplantation, VEGF165 mRNA expression was detected using RT-PCR. Neuronal apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nickel end labeling (TUNEL). CD34 and VEGF protein were detected using immunohistochemistry. Microvascular density in the cerebral cortex was measured based on CD34 positive cells. A radial arm maze test was performed from 30 postnatal days to evaluate long-term learning and memory functions. At 35 postnatal days, the rats were sacrificed for cerebral histological examinations by hematoxylin and eosin.</p><p><b>RESULTS</b>The expression of VEGF165 mRNA increased in the Ad-VEGF-treated group more than in the untreated HIBD and the buffer-treated groups (p<0.05). The number of apoptotic neurons was less in the Ad-VEGF-treated group compared with that in the untreated HIBD and the buffer-treated groups (p<0.05). Microvascular density and VEGF positive cells increased in the Ad-VEGF-treated group compared with that in the untreated HIBD and the buffer-treated groups (p<0.05). In the radial arm maze test, the Ad-VEGF-treated group had more improved achievements than the HIBD and the buffer groups (p<0.05). Neuronal degeneration and necrosis were lessened in the Ad-VEGF-treated group compared with the HIBD and the buffer groups.</p><p><b>CONCLUSIONS</b>Ad-VEGF gene transfer can increase the expression of VEGF mRNA and VEGF protein, decrease neuronal apoptosis, and increase angiopoiesis in the brain. This attenuates brain damage and improves long-term learning and memory functions in neonatal rats after HIBD.</p>
Texto completo:
Disponível
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Terapêutica
/
RNA Mensageiro
/
Terapia Genética
/
Córtex Cerebral
/
Adenoviridae
/
Química
/
Ratos Sprague-Dawley
/
Fármacos Neuroprotetores
/
Marcação In Situ das Extremidades Cortadas
/
Hipóxia-Isquemia Encefálica
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
Idioma:
Chinês
Revista:
Chinese Journal of Contemporary Pediatrics
Ano de publicação:
2008
Tipo de documento:
Artigo