神经生长因子经鼻脑靶向治疗创伤性脑外伤后大鼠认知功能障碍

目的创伤性脑损伤(traumatic brain injury,TBI)后常伴有认知功能障碍。文中探讨经鼻给予神经生长因子(nerve growth factor,NGF)对实验性TBI大鼠认知功能障碍的治疗作用。方法将大鼠随机分为假手术组、对照组和治疗组(NGF)。参照Feeney’s自由落体法制作TBI大鼠模型,治疗组给予经鼻给NGF治疗。采用Morris水迷宫方法评估3组TBI大鼠的认知功能情况。尼氏染色检测海马存活神经元,用ELISA法测定海马Aβ42含量,行免疫组化染色检测各组TBI大鼠海马Aβ42表达的情况。结果治疗组TBI大鼠与对照组相比,认知功能障碍明显减轻(P<0.05),尼氏染色观察发现海马存活的神经元细胞数目在对照组和治疗组均明显低于假手术组(P<0.05),治疗组明显高于对照组(P<0.05);ELISA和免疫组化观察发现海马Aβ42表达在对照组和治疗组均明显高于假手术组(P<0.05),治疗组明显高于对照组(P<0.05)。结论经鼻给NGF可增加TBI大鼠海马神经元的存活,减轻Aβ42沉积,促进损伤后认知功能的恢复。

Intranasal delivery of nerve growth factor for cognitive dysfunction after traumatic brain injury in rats

Objective Cognitive dysfunction frequently occurs after traumatic brain injury(TBI).This article aims to study the effect of intranasally delivered nerve growth factor(NGF) on cognitive dysfunction in rats with TBI.Methods TBI models were established in healthy adult SD rats using the modified method of Feeney′s weight-drop and then randomly divided into a sham,a control and a treatment group.The rats in the control group were given phosphate-buffered saline,and those in the treatment group intranasally administered NGF.The cognitive function of the three groups of rats was assessed by the Morris water maze test,the surviving neurons in the hippocampus identified by Nissl staining,the concentration of Aβ42 in the injured ipsilateral hippocampus measured by ELISA,and the expression of Aβ42 in the hippocampus detected by immunohistochemistry.Results Cognitive dysfunction was significantly milder in the treated than in the control rats(P<0.05).There were significantly fewer surviving neurons in the hippocampus in treatment and control groups than in the sham group(P<0.05),and more in the treatment than in the control group(P<0.05).The expression of Aβ42 was significantly higher in the control and treated rats than in the sham group(P<0.05),even higher in the treatment than in the control group(P<0.05).ConclusionIntranasal delivery of NGF can increase the survival rate of hippocampal neurons,regulate the overproduction of Aβ42,and thus improve the cognitive function after brain injury in rats.