The incidence of spinal cord injury is increasing year by year, and more and more attentions have been paid. Growth factors can promote the regeneration of nerve fibers and synapses, and they also play an important role in the treatment of spinal cord injury and the recovery of neurological function. The growth factor itself has a short half-life, so it is necessary to use growth factor gene vectors to transfect stem cells and nanoparticles to deliver growth factors or biocompatible scaffolds to support growth factors to treat spinal cord injuries. With the development of the research on growth factors, the application of single growth factor is difficult to meet the need of treatment to spinal cord injury. To explore the synergistic effect of various growth factors in order to achieve a better therapeutic effect is a promising research direction in the future. The purpose of this review is to summarize the therapeutic effects of growth factors on spinal cord injury including brain-derived neurotrophic factor, neurotrophic factor 3, nerve growth factor, basic fibroblast growth factor and synergy therapy of growth factors.

Objective To observe the therapeutic effect of combined acupuncture combined with omeprazole on patients with craniocerebral trauma complicated with stress gastric mucosal injury. Methods Patients with stress gastric mucosal injury after cerebral trauma admitted to neurology of Brain Hospital, Affiliated Hospital of Logistics University from June 2016 to July 2017 were enrolled, with the inclusion criteria within 24 hours after injury at admission, and Glasgow coma scale (GCS) less than 12. Patients were divided into omeprazole group, acupuncture group and acupuncture plus omeprazole combined treatment group according to random number table method. All patients in the three groups were given symptomatic treatment in time after admission. After diagnosis, omeprazole group was injected intravenously omeprazole, 40 mg each time, one dose in 12 hours for 7 days; acupuncture group was acupunctured at bilateral Zusanli point and Zhongwan point, 20 minutes for needle retention, once a day for 7 days;combined treatment group was given acupuncture and omeprazole at the same time. The GCS score and the occult stool test were performed at admission and treatment of 7 days; the pH of gastric juice, the levels of serum neurotensin (NT) and endothelin-1 (ET-1) were measured at admission and treatment 1, 3, 5, 7 days. At the same time, 10 healthy persons were selected as the control. Results Finally, 90 patients were selected, 30 in each group. GCS score at 7 days after treatment in omeprazole group, acupuncture group and combined treatment group were significantly higher than those at admission, but there was no statistical difference among the groups (9.46±2.81, 10.26±2.24, 10.52±2.50, F = 2.010, P = 0.141). For treatment of 7 days, the incidence of occult stool in the combined treatment group was significantly lower than that in the omeprazole group and acupuncture group (13.3% vs. 36.7%, 40.0%, both P < 0.05). The pH value of gastric excretion was increased gradually after treatment in the three groups. The pH value of gastric excretion in the combined treatment group was significantly higher than that in the omeprazole group and acupuncture group at 5 days of treatment (4.58±0.53 vs. 4.20±0.52, 4.28±0.43, both P < 0.05). The levels of serum NT in the three groups were both bi-directional: the level of NT at admission was significantly higher than that in the healthy control group, then decreased significantly, and the treatment of 3 days was significantly lower than that in the healthy control group and then rise gradually. The level of NT at treatment 5 days in the combined treatment group was significantly higher than that of the omeprazole group and the acupuncture group (ng/L: 45.88±8.03 vs. 36.15±11.54, 37.32±7.79, both P < 0.05), and had returned to normal level on the 7th day after treatment (ng/L: 56.88 ±12.54). The level of serum ET-1 in the three groups showed a bimodal change: the level of ET-1 at admission was significantly higher than that of the healthy control group. The treatment of 1 day to the normal range was gradually increased, and the peak of 5 days appeared again and then decreased slowly. The level of ET-1 at treatment of 7 days in the combined treatment group was significantly lower than that of the omeprazole group and acupuncture group (ng/L: 53.25±7.60 vs. 63.74±9.05, 65.50±12.73, both P <0.05), and had been restored to normal. Conclusion Combined acupuncture at points of Zusanli and Zhongwan for the treatment of stress gastric mucosal injury after traumatic brain injury, can reduce gastric acid secretion, promote the level of NT in serum, reduce the secretion of ET-1 level, help to repair the gastric mucosa, and the effect of combined with omeprazole is more significant.

Objective To explore the correlation between the changes of mitochondrial DNA (mtDNA) copy number of peripheral blood leukocytes and the degree of neurological impairment after traumatic brain injury (TBI).Methods A total of 40 Sprague Dawley rats were randomly divided into 4 groups:control group (n=10),mild TBI group (n=10),moderate TBI group (n=10) and severe TBI group (n=10).The cortical impact injury method to construct TBI rat model of different damage degree.The neurological score (mNSS,screen test,open field test) after TBI 24 h,48 h,72 h was performed and the orbital venous plexus blood genomic DNA was extracted.The real-time PCR method to measure the relative mitochondrial DNA copy number.After the experiment,the rats were euthanized,and the brain tissue was stained with hematoxylin-eosin staining(HE).Results There were significant differences in the HE staining findings of brain tissue pathology (P＜ 0.05).Each group of rats with brain injury after peripheral blood mtDNA copy number in 24 h (9.63±3.62,P＜0.05) and 48 h (9.80±3.58,P＜0.05) increased,began to decline at 72 h (4.97±2.68,P＜0.05).The rats mNSS scores were related with the mtDNA copy number after TBI 24 h (r=0.578,P＜0.05) and 48 h (r=0.559,P＜0.05),and not related to TBI 72 h (r=0.487,P＞0.05).The rats screen test scores were related with the mtDNA copy number after TBI 24 h (r=0.573,P＜0.05) and 48 h (r =0.501,P＜0.05),and not related to TBI 72 h (r=0.273,P＞0.05).The rats level scores of open field test were negatively correlated with the mtDNA copy number after TBI24 h (r=-0.662,P＜0.05) and 48 h (r=-0.507,P＜0.05),and not negatively correlated to TBI 72 h (r=-0.410,P＞0.05).The rats vertical scores of open field test were negatively correlated with the mtDNA copy number after TBI 24 h (r=-0.662,P＜0.05)and 48 h (r =-0.607,P＜ 0.05),and not negatively correlated to TBI 72 h (r =-0.141,P＞ 0.05).Conclusion TBI is related with the copy of early peripheral white blood cell number and mtDNA of rat nerve function damage,and mtDNA copy number of peripheral white blood cell may become a clinical evaluation of TBI neural function damage degree of a potential biomarker.

Objective To simulate the chemical microenvironment after traumatic brain injury (TBI) and to investigate the effect of this microenvironment on the survival and differentiation of neural stem cells (NSCs).Methods The brain tissue homogenate of TBI rat model was harvested to simulate the chemical microenvironment after TBI.The primary NSCs of rat model were isolated and extraction,and then identified the phenotype characteristics with immunofluorescence staining.The experiments were divided into control group,normal brain tissue extract group (BTE group) and traumatic brain injury tissue extract group (TBITE group).The cell growth and morphological changes of each group were observed dynamically.The expression of apoptosis related protein,which includes Bax,Bcl-2,caspase-3 and cleaved caspase-3,were detected by Western Blot 24 h after experiments.The proliferation of NSCs was detected by MTT assay and Western Blot after 3 days.The differentiation level of NSCs to neurons was detected by immunofluorescence staining after 7 days.Results The results of Western Blot showed that compared with the control group,there was no significant change of apoptosis in the BTE group,while the apoptosis in the BTE group was significantly increased,showed a increase of expression levels of Bax (F=18.06,P＜0.01) and Cleaved caspase-3 (F=23.86,P＜0.01),and a decrease of that of Bcl-2 (F=22.95,P＜0.01).The results of MTT assay showed that compared with the BTE group,the proliferation of NSCs in the TBITE group was decreased (F=41.99,P＜0.01).The immunofluorescence staining showed that compared with the control group,the neuronal differentiation rate was increased in the BTE group.Further,compared with the BTE group,the neuronal differentiation rate in the TBITE group was decreased (F=66.93,P＜0.01).Conclusion The injury microenvironment after TBI can significantly inhibit the survival and differentiation of NSCs,which provides a theoretical basis for clarifying the mechanism of endogenous nerve regeneration after TBI.

Objective To explore the effect and mechanism of necroptosis related proteins in middle cerebral artery occlusion (MCAO) induced brain ischemia/reperfusion injury in mice.Methods C57BL/6 mice were used to establish the brain ischemia/reperfusion injury model induced by MCAO.MCAO mice were treated with z-VAD.fmk (zVAD,1.1 g/kg),GSK'872 (0.7 g/kg) and combined intervention of zVAD and GSK'872,and neurological defect was evaluated by mNSS while brain infarct volume was measured by TTC staining.Western blot and immunofluorescence assay were used to detect protein expression and location of RIP1,RIP3 and MLKL,respectively.Results Neurological defect and brain infarction were caused by MCAO.Compared with MCAO group,zVAD,GSK'872 and the combined intervention alleviated neurological defect and reduced brain infarct volume significantly (P＜0.05 or P＜0.01).The protein levels of RIP3 and RIP1 MLKL were increased in mice of MCAO group,while GSK'872 and the combined intervention obviously downregulated the aforementioned protein expression [RIP1 (GSK'872:0.64± 0.02 vs MCAO:1.28±0.02,P＜0.01);RIP3 (GSK'872:1.08±0.02 vs MCAO:1.45±0.02,P＜0.01);MLKL (GSK'872:0.54±0.01 vs MCAO:1.00±0.01,P＜0.01)].However,zVAD only slightly reduced protein expression of MLKL (P＜0.05) but didn't change the protein expression of RIP1 and RIP3 (P＞0.05).Conclusion RIP1,RIP3 and MLKL are involved in the execution of necroptosis and contribute to the pathological progress of brain ischemia/reperfusion injury.

Objective The incidence of traumatic brain injury (TBI) has been on the rise year by year around the globe.According to the latest Guidelines for the Management of Severe Traumatic Brain Injury (Fourth Edition) released by the Brain Trauma Foundation (BTF),there is no sufficient evidence that related medicine can promote the repairment of neural injury in the treatment of central nerve damage.The clinical treatment of TBI is facing multiple difficulties.In recent years,brain computer interface (BCI) technology has developed rapidly and shown enormous potential in TBI repairment,especially in visual and auditory restoration,neural function recovery,and cognitive restoration.BCI provides a new approach to improve the quality of life for patients.This paper reviews the application and prospect of BCI in sense,motion,and cognitive function repairment after TBI,so as to provide new insights for the treatment of TBI nerve function.

Objective To explore the effects of different doses of dexmedetomidine on acute brain edema in mice with traumatic brain injury (TBI).Methods A total of 132 male C57BL/6J mice were randomly divided into six groups:control group (group C),sham-operation group (group Sham),traumatic brain injury group (group TBI),Dex 20 μg/kg (group D20),40 μg/kg (group D40),and 60 μg/kg (group D60),n=22 in each group.The TBI animal model was established by electric controlled cortical impactor (eCCI),then intraperitoneal injected by the administration of different doses of dexmedetomidine at 0,2 and 4 h after TBI.Twenty-four hours post-TBI,brain water content was measured by the dry-wet method,histological observation was performed using HE staining,and aquaporin 4 (AQP4) and NF-κB expression were detected using Western blot assay,respectively.Then,the modified neurological scale scores (mNSS) on 1,2,3,and 7 d and Morris water maze (MWM) test on 4,5,6 and 7 d post-TBI were used to evaluate the neurologic deficit of TBI mice.Results After traumatic brain injury,the mNSS scores,the escape latency,the brain water content and the expression of AQP4 and NF-κB increased significantly in group TBI (P＜0.01).Different doses of dexmedetomidine significantly reduced the mNSS scores,the escape latency,the brain water content and the expression of AQP4 and NF-κB (P ＜ 0.05 or P ＜ 0.01).And meanwhile dexrnedetomidine can lessen neuronal degeneration,and inflammation response.Additionally,the effect was remarkably in group D60 compared with group D20 (P ＜ 0.05 or P ＜ 0.01).Conclusion Dexmedetomidine can lessen brain edema and cognition impairment induced with traumatic brain injury,which is a dose-effect relationship within 20-60 μg/kg,and this effect may be related to the downregulation of AQP4 and NF-κB expression.