Treatment of acute cerebral infarction by intranasal administration of nerve growth factor into central nervous system / 医学研究生学报

ABSTRACT

Objective:To study the reliability and feasibility of intranasal(IN)pathway bypassing the blood-brain barrier (BBB) and observe the potential neuroprotective effects of intranasal NGF on acute cerebral ischemia. Methods:A blinded, vehicle-controlled study of IN NGF and IV NGF administration was performed by intraluminal middle cerebral artery occlusion (MCAO) model. Experiment 1 Rats were randomly divided into IN NGF, IV NGF and untreated group (n=4). The concentration of NGF in different brain regions was measured by ELISA. Experiment 2 Rats were randomly assigned into 4 groups IN vehicle, IN NGF, IV vehicle, IV NGF (n=8 each). Treatments was initiated 30 min after the onset of MCAO and then again 24 h later. Three neurologic behavioral tests were assessed at 24 h and 48h. Corrected infarct volumes were determined 48 h after the onset of MCAO. Results:Olfactory bulb in IN NGF group obtained the highest concentration among all tissues, arriving at 3 252 pg/g, followed by hippocampus. The NGF concentrations of olfactory bulb and hippocampus in IN NGF group were significantly higher than that in IV NGF and control group. The infarct volume in IN NGF group was reduced significantly by 38.8% as compared with IN vehicle. The vestibulomotor function of IN NGF improved significantly at 24 and 48 h (P=0.02 and P=0.04, respectively). Conclusion:Intranasal NGF could bypass BBB, reach the CNS, reduce infarct volume and improve neurological function in rats following MCAO. Intranasal delivery of NGF holds a promising treatment for stroke and other CNS disorders.