Protective Effects Of Nerve Growth Factor On Newborn Rats With Hypoxia-ischemic Brain Damage

Objective1 To study the effects of nerve growth factor (NGF) on the expressions of Nestin and vascular endothelial growth factor (VEGF) in hypoxic-ischemic rat brain; 2 To explore the mechanism of NGF on the expression of Nestin and VEGF in hypoxic-ischemic rat brain; 3 To probe into the mechanism of how does NGF work in hypoxic-ischemic brain damage(HIBD).MethodsEighty four 7-day postnatal SD rats were randomly divided into 3 groups: shamsurgery (n=28), hypoxic-ischemic brain damage (n=28) and NGF-treated groups (n=28).Immediately after hypoxic-ischemic insult, 6000U/Kg per rat NGF or same injection dose of normal saline solution was injected intraperitoneally once a day for 7 days. The shamsurgery group was not administrated. The pups were perfused at immediantely, 3h, 12h, 24h, 3d, 7d, 14d of recovery from hypoxic-ischemia. Immunohistochemical technical was applied to investigate the changes of expression of Nestin and VEGF in cerebral tissues.ResultsThe expression of Nestin from cortex, hippocarapal, and extraventricular zone in HIBD groups were up-regulated and peaked at 7d after HIBD, demonstrating significant differences at 12h, 24h, 3d and 7d compared with that observed in the shamsurgery group(p<0.05). Nestin expression in the NGF-treated group increased markedly in these sites at 12h and peaked at 3d after HIBD compared with that in the HIBD groups, which reached a maximum at 7d(p<0.05). VEGF immunoreactive positive cells were nearly not found in the brain tissue of shamsurgery group.The expression of VEGF occurred at immediately after HIBD in cortex and hippocampal, peaked at 12h, remained to 12h, then decreased after 24h in HIBD group. The level of VEGF peaking at 3h in the NGF-treated group was significantly higher than that in the HIBD group(p<0.05) and different in recovery intervals. The level of VEGF demonstrated significant difference at immediately after HIBD, 3h, 12h, 24h, 3d(p<0.05) Compared with that in HIBD group.ConclusionThe protective effects of NGF which promote the nerve function recovery on hypoxic-ischemic brain damage are established. NGF can participat in regeneration and remolding of the nerve, it can induce the proliferation of endothelial cell resulting in Hypervascularization as well. The protective effects of NGF on the newborn rats with hypoxic-ischemic brain damage may be related to the rising expression of Nestin and VEGF.