神经生长因子经鼻脑靶向联合骨髓干细胞自体动员治疗重型颅脑损伤

Interventions for severe craniocerebral injury by nasal administration of nerve growth factor combined with bone marrow stem cell mobilization

背景:经鼻脑靶向给药是一种新型给药方法,可以绕开血脑屏障,直接作用于中枢神经系统,不仅具有良好的脑靶向性,还具有无创、快捷的优点。研究表明神经生长因子联合骨髓干细胞动员治疗脑损伤有协同作用。目的:观察神经生长因子经鼻脑靶向联合自体骨髓干细胞动员及综合康复治疗重型颅脑损伤的疗效。方法:(1)选择河南省人民医院神经外科收治的资料完整的创伤性脑损伤患者78例,根据治疗方案不同分为2组:对照组39例采用神经生长因子肌肉注射,1次/d,持续28 d,联合自体骨髓干细胞动员治疗;观察组39例采用神经生长因子经鼻脑靶向滴入,1次/d,连续给药28 d,联合自体骨髓干细胞动员治疗;(2)自体骨髓干细胞动员治疗方案:在脑损伤1周后皮下注射重组人粒细胞集落刺激因子或重组人巨噬细胞集落刺激因子,每3 d 1次,2种交替,同时配合辛伐他汀片10 mg/d口服,连续28 d;(3)出院后2组患者继续行神经生长因子治疗3个月。结果与结论:(1)患者治疗28 d时,观察组神经功能缺损评分略低于对照组,差异无显著性意义(t=0.429,P>0.05);(2)治疗3个月后NIHSS评分,观察组显著优于对照组(t=7.176,P<0.05);(3)格拉斯哥评分(GOS)观察组明显高于对照组(P<0.05);(4)两组患者治疗与随访期间均未出现明显不良反应。(5)结果说明,神经生长因子经鼻脑靶向联合自体骨髓干细胞动员及康复治疗能有效促进重型颅脑损伤的修复,显著改善患者神经功能。

BACKGROUND： Nasal administration is a new route of administration in which drugs can bypass the blood-brain barrier and act directly on the central nervous system. It not only has good brain targeting but also has the advantages of being non-invasive and convenient. Studies have shown that nerve growth factor （NGF） combined with bone marrow stem cell （BMSC） mobilization has a synergistic effect on brain injury. OBJECTIVE： To observe the therapeutic effect of NGF combined with autologous BMSC mobilization via nasal administration and comprehensive rehabilitation for severe craniocerebral injury.METHODS： Seventy-eight patients with traumatic brain injury from the Department of Neurosurgery of Henan Provincial People’s Hospital were selected and treated with NGF intramuscular injection （once a day, for continuous 28 days） combined with BMSC mobilization and comprehensive rehabilitation therapy as control group （n=39） or treated with NGF through the nasal administration （once a day, for continuous 28 days） combined with BMSC and comprehensive rehabilitation treatment as observation group （n=39）. Therapeutic schedule for autologous BMSC mobilization was as follows： subcutaneous injection of recombinant human granulocyte colony-stimulating factor or recombinant human macrophage colony-stimulating factor alternately at 1 week after brain injury, once every 3 days, and oral administration of simvastatin tablets, 10 mg per day, for continuous 28 days. Two groups of patients continued to be treated with NGF for 3 months after discharge. RESULTS AND CONCLUSION： At 28 days after treatment, the neurologic defect score in the observational group was slightly lower than that in the control group, but there was no significant difference between the two groups （t=0.429, P 〉 0.05）. At 3 months after treatment, the score on the National Institutes of Health Stroke Scale was significantly better in the observational group than the control group （t=7.176, P 〈 0.05）, and the score on the Glasgow Coma Scale Glasgow was also significantly higher in the observational group than the control group （P 〈 0.05）. No obvious adverse event occurred in the two groups during the treatment and follow-up. To conclude, nasal administration of NGF combined with autologous BMSC mobilization and rehabilitation therapy can effectively promote the repair of severe craniocerebral injury and significantly improve the neurological function of the patients.