经鼻腔给予神经生长因子治疗急性脑梗死的实验研究

目的 :探讨经鼻腔 (IN)给予神经生长因子 (NGF)避开血 脑屏障 (BBB)进入中枢的可行性 ,证实进入各脑区的NGF对急性脑梗死是否具有神经保护效应。　方法 :SD大鼠采取线栓法制作大脑中动脉闭塞模型 (MCAO) ,在随机双盲状态下分组予以不同处理。利用酶联免疫吸附法 (ELISA)测定经鼻腔和静脉注射NGF后各脑区的NGF浓度 ,通过行为学评分和测定脑梗死体积来判定IN给予NGF对于急性缺血性脑损伤的疗效。　结果 :INNGF组嗅球部位的NGF浓度最高 ,达 32 5 2pg/g ,其次为海马。嗅球与海马部分的浓度与静脉注射 (IV)NGF组及对照组相比显著增高 (P <0 .0 1)。INNGF组的脑梗死体积明显减小 ,与对照组相比降低了 38.8% (P =0 .0 0 2 ) ,IVNGF组与对照组相比无显著差异。INNGF组的运动平衡功能在脑缺血后 2 4h和 4 8h时与对照组相比均得到显著改善 (P =0 .0 2 ,P =0 .0 4 )。IVNGF组各项神经功能评分与对照组相比均未见明显差异。　结论 :IN给予的NGF可以避开BBB的阻碍 ,进入各脑区和脊髓上颈节段 ,能够有效地降低脑梗死体积 ,并在一定程度上促进神经功能的恢复 ,对于脑梗死的治疗具有显著的神经保护效果。

Treatment of acute cerebral infarction by intranasal administration of nerve growth factor into central nervous system

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.