Therapeutic time window for the neuroprotective effects of NGF when administered after focal cerebral ischemia
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In the present study, we evaluated the neuroprotection time window for nerve growth factor (NGF) after ischemia/reperfusion brain injury in rabbits as related to this anti-apoptosis mechanism. Male New Zealand rabbits were subjected to 2 h of middle cerebral artery occlusion (MCAO), followed by 70 h of reperfusion. NGF was administered after injury to evaluate the time window. Neurological deficits, infarct volume, neural cell apoptosis and expressions of caspase-3 and Bcl-2 were measured. Compared to saline-treated control, NGF treatment at 2, 3 and 5 h after MCAO significantly reduced infarct volume, neural cell apoptosis and expression of caspase-3 (P < 0.01), up-regulated the expression of Bcl-2 and improved functional recovery (P < 0.01). However, treatment at latter time points did not produce significant neuroprotection. Neuroprotection treatment with NGF provides an extended time window of up to 5 h after ischemia/reperfusion brain injury, in part by attenuating the apoptosis.
KeywordsFocal cerebral ischemia Nerve growth factor Neuroprotection Time window Bcl-2 Apoptosis
This study was supported by the China Ministry of Health Science Foundation (#200310, Dr. Liu), Hebei Natural Science Foundation (#C2010000557, Dr. Yang), Hebei Key Program of Medical Research (#20090101, Dr. Yang) and China Postdoctor Science Foundation (#20070411051, Dr. Yang).
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