亚低温对重型颅脑创伤患者血清抗脑抗体含量的影响

目的 研究重型颅脑创伤(sTBI)后患者血清抗脑抗体(ABAb)浓度变化及亚低温治疗对血清ABAb浓度的影响,探讨亚低温脑保护机制.方法 选择80例sTBI住院患者,随机分成常温治疗(NT)组和亚低温治疗(HT)组各40例,分别予以常温治疗和亚低温治疗,于伤后第1、3、5、7、14天采血.用酶联免疫吸附(ELISA)法测定血清ABAb浓度,观察各时间点血清ABAb浓度的变化,分析各时间点两组血清ABAb浓度与格拉斯哥预后评分(GOS)的相关性.另取20例健康体检者作为对照组.结果 (1)所有sTBI患者在伤后各时间点血清ABAb浓度高于正常对照组(P＜0.01).(2)HT组于伤后各时间点血清ABAb浓度低于NT组,且差异有统计学意义(P＜0.01).(3)NT组于伤后各时间点血清ABAb浓度与GOS评分呈负相关,出院时HT组预后也较NT组为佳.结论 HT能够降低sTBI患者血清ABAb含量,具有脑保护作用,其脑保护机制可能与HT能减轻血清ABAb介导的损伤性脑细胞炎性反应有关.

Abstract：

Objective To disclose the Probably protective mechanism of mild hypothermia protecting brain through investigating the contents charges of Antibrain-Antibody(ABAb)in serum in patients with severe traumatic brain injury(sTBI) and the influence of mild hypothermia on serum levels of ABAb.Methods A total of 80 cases with sTBI were treated with normothennia - treated (NT) (NT group, re =40)and mild hypothermia( HT) (HT group, n =40) respectively. ELISA was used to measure serum levels of ABAb. Groups at 1、3、5、7 and 14 days after injury to observe the contents changes of ABAb in serum and the influence of mild hypothermia. Simultaneous analysis two groups at each time point of serum ABAb concentration and Glasgow outcome scale (GOS) of relevance was performed Contrast analysis of clinical prognosis for patients in the two groups was carried out to reveal the protective mechanism of mild hypothermia protecting on patients with sTBL 20 serum specimens of normal persons were used as control group. Results (1) All sTBI patients at each time point after injury, serum ABAb levels were higher than the normal control group ( P ＜0.01). (2) Concentration of antibodies in the serum ABAb levels in HT group at each time point was lower than in NT group( P＜0.01). (3) Concentration of serum ABAb levels in NT group at each time point of injury was negatively correlated with the GOS score; prognosis at discharge in HT group was better than in NT group. Conclusions HT can reduce the serum ABAb levels in sTBI patients, improve the prognosis, have brain protective effect The brain protective mechanisms may be related to the mild hypothermia which reduce the serum ABAb - mediated inflammatory damage on brain cells.     

Changes of biochemical indices in brain, liver tissue and serum in mice with Alzheimer disease after Chinese medicine treatment

BACKGROUND: Alzheimer disease is a main type of dementia, and the important clinical characteristic is the rapid declines of memory and cognitive ability. OBJECTIVE: To study changes of biochemical indices in brain, liver tissue and serum, as well as memory of mice with Alzheimer disease after Chinese medicine treatment. DESIGN: A comparative animal experimental observation. SETTING: Haierfu Research Center of Youjiang Medical College for Nationalities. MATERIALS: Forty-eight healthy Kunming mice (24 males and 24 females), 3 months old, were provided by the animal room of Youjiang Medical College for Nationalities. The animals were divided into four groups according to sex and body mass: control group, model group, Wuyuan Buxue treated group, Haierfu treated group, and 12 mice in each group. Wuyuan Buxue oral liquid was extracted from Polygonum multiflorum Thunb (red, radix) and longan meat (country medicine quasi- word B20020828). Haierfu oral liquid was extracted from Yinhua, poriacocos, licorice, etc (Q/452600RYYLC01-92). METHODS: The experiment was completed in Haierfu Research Center and Institute of Heavy Metal and Fluorosis-Arsenism of Youjiang Medical College for Nationalities from May 2006 to December 2006. ① All animals except those in the control group were given feed which was mixed with AlCl3 (12 g/L), and they could freely drink 3 g/L Al(NO3)3. The mice in the control group were given normal feed. Wuyuan Buxue oral liquid and Haierfu oral liquid were distilled by distilled water for one time respectively. Five months after model establishment, mice in the Wuyuan Buxue treated group and Haierfu treated group were given intrapastric perfusion of Wuyuan Buxue oral liquid and Haierfu oral liquid respectively, and those in the model group and control group were given intrapastric perfusion of distilled water of the same volume. All the mice were treated for 45 days. ② The swimming time (s) and error times were determined with Y-shape water maze before and after experiment; Hemoglobin was determined by method of HICN. After treatment, serum was isolated from eyeballs to determine the activities of glutathione peroxidase (GSH-PX), urea and cholesterol. The animals were executed to remove brain and liver, then 10% homogenate was prepared to determine the activity of acetylcholinesterase (AChE), clearance of O2–?, content of malondialdehyde (MDA), activities of superoxide dismutase (SOD) and GSH-PX. MAIN OUTCOME MEASURES: ① Swimming time and error times in the water maze, and the content of hemoglobin; ② alanine aminotransferase (ALT) activity and contents of urea and cholesterol in serum after treatment; ③ Activities of GSH-PX, AChE and SOD, and MDA content in liver, and AChE activity in brain after treatment. RESULTS: Totally 48 mice were used, and some of them died due to unknown reasons, finally 32 mice (8 in each group) were involved in the analysis of results. ① Content of hemoglobin before and after treatment: There were obvious changes in the groups (P < 0.05). ② Comparison of ALT, cholesterol and urea in serum: The contents of urea in the Wuyuan Buxue treated group and Haierfu treated group were obviously higher than those in the control group and model group (P < 0.05, 0.01); ALT and cholesterol had no significant differences among the groups (P > 0.05). ③ Comparisons of the activities of AChE, GSH-PX and SOD in brain homogenate: The activity of AChE was significantly higher in the control group than the model group and Haierfu treated group, also higher in the Wuyuan Buxue treated group than in the model group (P < 0.05). The activity of GSH-PX in the model group was significantly higher than those in the treated groups (P < 0.01). The activity of SOD in the control group was significantly higher than those in the treated groups (P < 0.05, P < 0.01). ④ Comparison of activities of GSH-PX and SOD, and MDA content in liver homogenate: The activities of GSH-PX and SOD in the model group were obviously lower than those in the Wuyuan Buxue treated group (P < 0.05). MDA content had no obvious differences among the groups (P > 0.05). ⑤ Comparison of MDA content, and clearance of O2–? in brain and liver: The MDA content in brain in the model group was significantly higher than those in the treated groups; The clearances of O2–? in liver in the treated groups were significantly higher than those in the control group and model group (P < 0.01). ⑥ Swimming time and error rate in water maze: Before treatment, the swimming speed had no obvious difference among the groups, while the error rate was obviously different. After treatment, there was no obvious difference in the control group; The swimming time was prolonged as compared with that before treatment in the other three groups, and there were no obvious differences among the three group; The error rate was the highest in the model group (25%), and the lowest in the Wuyuan Buxue treated group (8.3%). CONCLUSION: Both the Chinese medicines of Wuyuan Buxue oral liquid and Haierfu oral liquid can improve the biochemical indices in serum, liver and brain, and the memory ability of mice with Alzheimer disease.     

双侧平衡去骨瓣减压术对特重型颅脑伤致双瞳散大患者的救治

目的 探讨双侧平衡去骨瓣减压术在治疗特重型颅脑外伤致双瞳散大患者中的作用.方法 对我科2005年1月至2010年12月收治的58例单侧损伤灶所致特重型颅脑外伤致双瞳散大手术患者进行回顾性分析,其中2005年1月至2007年9月仅行病灶侧去骨瓣减压术30例(A组),2007年10月至2010年12月采用双侧平衡去骨瓣减压术28例(B组),分析并比较两组患者颅内压、预后及并发症情况.结果 采用双侧平衡去骨瓣减压术者较仅对血肿侧去骨瓣减压者颅内压下降差异有统计学意义;死亡率下降了25.2%,预后良好率上升了26.9%.结论 双侧平衡去骨瓣减压术可有效降低特重型颅脑外伤致双瞳散大患者的颅内压,减少急性脑膨出和脑梗死的发生率,降低死亡率.

Abstract：

Objective To explore the effect of bilateral balanced decompressive craniectomy in treatment of the most severe brain injured patients with bilateral mydriasis. Methods Fifty - eight cases of the most severe brain injury due to unilateral lesions with bilateral mydriasis were analyzed retrospectively from Jan 2005 to Dec 2010. Thirty were treated by unilateral decompressive craniectomy from Jan 2005 to Sep 2007(group A) and 28 by bilateral balanced decompressive craniectomy from Oct 2007 to Dec 2010(group B). The intracranial pressure, prognosis and complications were compared. Results Postoperative ICP was significantly lower in group B than group A; patients in group B had a lower mortality and better outcome than in group A. Conclusion Bilateral balanced decompressive craniectomy can efficiently reduce the values of ICP, occurrence of acute encephalocele and brain infarction and mortality of the most severe brain injured patients with bilateral mydriasis.     

BDNF-TAT融合蛋白在大肠杆菌中的表达纯化及脑中分布

目的 在大肠杆菌中表达并纯化BDNF-TAT融合蛋白,研究其靶向性及在脑中的分布.方法 重组质粒PET-30(a)-BDNF-TAT转染至大肠杆菌BL21(DE3)pLysS中,IPTG诱导其表达后用SP-Sepharose阳离子交换柱纯化,纯化后蛋白用0.4 mol/L精氨酸倍比稀释法复性.KM种小鼠采用随机数字表法分为给药组[尾静脉注射复性后BDNF-TAT融合蛋白4 μg(适量生理盐水溶解)]、阴性对照组(尾静脉注射等体积生理盐水)和空白对照组(不进行任何处理),每组各3只.3 h后提取小鼠脑组织全蛋白,Western blotting检测脑组织中BDNF-TAT表达,SABC免疫组化染色观察BDNF-TAT在脑组织中的分布.结果 获得纯度约90%活性的BDNF-TAT融合蛋白.给药组BDNF-TAT蛋白的相对表达最为1.897±0.286,阴性对照组BDNF-TAT蛋白的相对表达量为0.615±0.234,空白对照组BDNF-TAT蛋白的相对表达量为0.335±0.154,比较差异有统计学意义(F=39.019,P=0.0000).免疫组化染色结果显示给药组BDNF-TAT主要分布于小鼠脑组织海马CA1、CA3和DG区,而阴性对照组和空白对照组巾没有明显阳性染色.结论 BDNF-TAT融合蛋白在大肠杆菌中以包涵体形式大量表达,并能通过外周给药靶向至小鼠脑组织.

Abstract：

Objective To explore the expression and purification of BDNF-TAT fusion protein in E.coli, and study its brain-targeting and distribution in brain. Methods Plasmid PET-30(a) -BDNF-TAT was transfected into the E.coli BL21 (DE3)pLysS;the expression of PET-30(a)-BDNF-TAT was induced by isopropyl-beta-d-thiogalactopyranoside (IPTG);this BDNF-TAT fusion protein was purified by SP-Sepharose cation exchange column and then renatured by 0.4 mol/L arginine. According to the random number table method, KM mice were divided into 3 groups: BDNF-TAT treatment group (giving 4 μg BDNF-TAT through intravenous injection, n=3), negative control group (giving same volume of saline through intravenous injection, n=3) and blank control group (without giving any treatment, n=3). The whole brain protein was collected 3 h after the injection;Western blotting was used to identify the expression of BDNF-TAT fusion protein;the distributions of BDNF-TAT in the brain tissues were examined by SABC immunohistochemistry. Results BDNF-TAT fusion protein was purified with the purity about 90%. The relative expression of BDNF-TAT fusion protein was 1.897±0.286 in the BDNF-TAT treatment group, 0.615±0.234 in the negative control group, 0.335±0.154 in the blank control group;significant differences between each 2 groups were noted (F=39.019, P=0.000).Western blotting indicated that the content of BDNF-TAT in the mice brain in BDNF-TAT treatment group was obviously higher than that in the negative control group and blank control group (P<0.05);BDNF-TAT fusion protein were widely distributed in CA1,CA3 and DG areas of the hippocampus of brain tissues in the BDNF-TAT treatment group, while no obvious positive staining was noted in the negative control group and blank control group. Conclusion BDNF-TAT fusion protein abundantly expresses in E.coli in the form of inclusion bodies, and can target the brain tissue via a systemic route.     

雌激素对实验性自身免疫性脑脊髓炎小鼠的治疗作用及对基质金属蛋白酶-9表达的影响

目的 探讨雌激素对实验性自身免疫性脑脊髓炎(EAE)小鼠中枢神经系统(CNS)中基质金属蛋白酶-9(MMP-9)表达的影响.方法 用MeG35-55多肽诱发60只EAE小鼠模型,做去卵巢术.分为治疗组和对照组,治疗组予雌激素治疗.比较2组EAE小鼠的临床症状评分.取脑和脊髓,行HE染色观察各组EAE小鼠炎症反应;实时荧光定量PCR及免疫荧光染色法检测各组EAE小鼠CNS中MMP-9的表达.结果 治疗组EAE小鼠与对照组相比临床症状减轻(治疗组3.23±0.83,对照组1.62±1.00,t=3.811,P＜0 05)、发病率降低(治疗组8/30,对照组28/30);HE染色显示治疗组炎症细胞浸润(急性期0.895±0.206,缓解期0.752±0.302,慢性期0.732±0.183)较对照组(急性期3.472±0.635,缓解期2.881±0.662,慢性期1.891±0.482)减少(t=8.622、6.543、5.027,均P＜0.01),实时荧光定量PCR及免疫荧光染色结果示治疗组EAE小鼠CNS中MMP-9表达降低.结论 雌激素能抑制EAE小鼠CNS中MMP-9的表达,减轻EAE小鼠临床症状及炎症反应.

Abstract：

Objective To study the regulation effect of estrogen in expression of matrix metalloproteinase-9 (MMP-9) in the central nervous system (CNS) in mice with experimental autoimmune encephalomyelitis ( EAE).Methods The 60 mice were overiectomized and 2 weeks later EAE was induced with MOG35-55 peptide in these mice.They were divided into a treatment group and a control group.The treatment group was treated with estrogen and the control group was given PBS.Clinical symptoms in these two groups were scored and compared.HE staining was used to observe inflammation in the brain and spinal cord.The MMP-9 expression in the CNS was examined by quantitative real-time PCR and immunofluorescence staining.Results The incidence of disease was lower (treatment and control group were 8/30 and 28/30 respectively) and clinical symptoms were milder (treatment and control group were 3.23±0.83 and 1.62 ±1.00 respectively,t=3.811 and P＜0.05) in the treatment group than those in the control group.HE staining showed the decreased infiltration of inflammatory cell in the treatment group (Treatment group:inflammatory score were 0.895 ±0.206,0.752 ±0.302,0.732 ±0.183 in acute,relief and chronic phase respectively;Control group:inflammatory score were 3.472 ±0.635,2.881 ±0.662,1.891 ± 0.482 in acute,relief and chronic phase respectively.t = 8.622,6.543 and 5.027,all P ＜ 0.05).The quantitative real-time PCR and immunofluorescence staining showed that the expression of MMP9 in the CNS was decreased in the treatment group.Conclusion Estrogen may decrease MMP-9 expression in the CNS,reduce inflammation and clinical symptoms in mice with EAE.     

Distinct proteins in cortex of rats with closed traumatic brain injury detected by a WCX-2 protein chip

BACKGROUND: Mechanical injury can cause the changes of polygene expression spectrum in rat cerebral cortical nerve cells, and then result in the changes of intracellular protein expression. At present, dielectrophoresis is combined with mass spectrum technique to detect the expression of different proteins in rat cortex after brain injury, but the protein chip technique requires further investigation. OBJECTIVE: To analyze the differences of protein expression spectrum in rat cerebral cortex before and after closed traumatic brain injury using WCX-2 protein chip technique. DESIGN: A randomized controlled animal experiment. SETTING: Training Division of the Medical College of Chinese People's Armed Police Force. MATERIALS: Seventy-two male SD rats of clean degree, 350–450 g, were provided by the Experimental Animal Center, Academy of Military Medical Sciences of Chinese PLA. Urea, trifluoroacetic acid, CHAPS and Tris (Sigma, USA); WCX-2 (Ciphergen, USA). Ultra-high speed hypothermia centrifuger (Bechman, USA); Rotary tissue microtome (Keuca, Germany); Biochip processor and PBSⅡ-C protein chip reader (Ciphergen, USA). METHODS: The experiments were carried out in the Institute of Molecular Pathology, Central Laboratory, and Department of Pathology, Medical College of Chinese People's Armed Police Force from June 2005 to March 2006. ① Grouping and treatment: The experiments were completed in molecular pathological institute, central laboratory and pathological department. ① The rats were randomly divided into control group (n =12) and brain injury group (n =60). Marmarou's weight-dropping models were duplicated at different time points in the brain injury group. In the control group, the rats were only treated by incising the skin of head top, without fixing the stainless steel hitting backup plate at the vault of skull, and obtain brain cortex for pathological and protein chip research, and they were killed after 24 hours. The rats in the brain injury group were killed at 4, 8, 12, 24 and 48 hours after model establishment. ② Pathological observation: Longitudinal section was made on cerebral cortex, and sections of 5 μm were prepared, then stained with hematoxylin and eosin (HE). ③ Protein chip analysis: 100 mg cerebral cortex was collected from each rat, and the protein content in sample was detected with Bradford method, meanwhile, WCX-2 protein chip was used to analyze the protein spectrum. The data were automatically collected with Ciphergen proteinchip 3.0 software, and the results were analyzed using Biomarker Wizard software to compare the differences of protein spectrum in rat cortex between the groups. MAIN OUTCOME MEASURES: Results of the pathological observation of cerebral cortex and the protein spectrum analysis. RESULTS: ① Pathological changes of cerebral cortex: In the control group, no necrosis and edema was observed. In the brain injury group, injures of different severity occurred at different time points; After 4 hours, focal or scattered red nerve cells could be observed, the size of some cells was increased, cytoplasm was lightly stained, and only nuclear fragments were seen; After 8 hours, the necrotic nerve cells were increased, and the number of nerve cells was reduced, astrocytes (neuronophagia) could be seen in partial cytoplasm; there was small vascular dilatation, and endothelial cell proliferation; interstitial edema, regional rarefaction lightly stained. After 12–48 hours, the necrotic nerve cells were reduced, and astrocytes proliferated. ② Results of protein spectrum analysis: The WCX-2 experiment found that the expressions of 5 639, 3 212 and 7 536 u proteins in cerebral cortex changed after injury in the brain injury group. The peak intensity of 5 639 u protein in the brain injury group at 8 hours after injury was higher than that in the control group (P < 0.05); The peak intensity of 3 212 u protein in the brain injury group at 48 hours after injury was higher than that in the control group (P < 0.05); The peak intensity of 7 536 u protein at 24 hours after injury was higher than that in the control group (P < 0.05). CONCLUSION: Brain injury can cause the changes of protein expression spectrum in cerebral cortex, it is suggested that brain injury can induce the expression of protein.     

Effect of zinc protoporphyrin on carbon monoxide/heme oxygenase-1 system in rats subjected to recurrent febrile convulsion

BACKGROUND: Studies on febrile convulsion (FC)-caused brain injury are disputed in many aspects. How FC cause nervous system injury in the developmental period and what are the characteristics of these pathological injury are unknown. The current studies have demonstrated that heme oxygenase-1 (HO-1) exerts effects on brain injury mainly by catalyzing hemoglobin to produce degradation products, and HO-1 not only has neuroprotective effects, but also has neurotoxic effects during the FC-caused brain injury. Study on the effect of zinc protoporphyrin (ZnPP) on brain injury is still in the stage of animal experiment. OBJECTIVE: To observe the effects of ZnPP on carbon monoxide (CO)/HO-1 system of rats subjected to FC, and to analyze the action pathway of ZnPP in brain protective effect. DESIGN: A randomized controlled animal experiment. SETTING: Department of Pediatrics, First Hospital Affiliated to Jiamusi University. MATERIALS: Sixty-five Wistar rats, of either gender, were involved in this study. They were randomized into normal control group( n =14, 37 ℃ water bath) and febrile treatment group (n =51, 44.5 ℃ hot water bath). Febrile treatment group was sub-divided into febrile non-convulsion group (FNC group, n =16) and FC group (n =35). FC group was further sub-divided into simple convulsion group (n =20) and ZnPP treatment group (n =15). HO-1 mRNA in situ hybridization kit was provided by Boster Bioengineering Co.,Ltd. ZnPP(dark brown powder) was the product of Jingmei Bioengineering Company. METHODS: This study was carried out in the postgraduate laboratory of Jiamusi University between January 2004 and January 2007. Rats in the febrile treatment group were placed in the 44.5 ℃ hot water bath box. If rats did not convulse in the water within 5 minutes, they were taken out, namely FNC group (n = 16), and those, which were convulsed within 5 minutes, were taken out immediately when they presented such a phenomenon, namely FC group (n =35). Convulsion induction was conducted once every other day, totally 10 times. Rats were euthanized for analysis at 24 hours after the last induction. Rats in the control group were placed in the 37 ℃ water. Rats in the ZnPP treatment group were intraperitoneally injected with ZnPP at 45 μmol/kg before FC attack. Rats in the simple convulsion group were only induced to be convulsed but not administrated. MAIN OUTCOME MEASURES: CO level in the brain tissue homogenate and plasma of rats in each group was detected with a spectrophotometer. HO-1 mRNA expression in the hippocampal CA1 region, CA3 region and dentate gyrus of rats was observed by in situ hybridization technique. RESULTS: Sixty-five Wistar rats were involved in the study. Two rats died respectively due to drowning and convulsion in the FC group. One rat died due to convulsion drowning in the ZnPP treatment group. ① Plasma CO concentration of control group and ZnPP treatment group was significantly lower than that of the FC group (P < 0.01), and was significantly higher in the ZnPP treatment group than in the FNC group (P < 0.05). ② CO level in the brain tissue homogenate was significantly lower in the control group and ZnPP treatment group than in the FC group (P < 0.01), and was very significantly higher in the ZnPP treatment group than in the control group (P < 0.01). ③ HO-1 mRNA expressions in the neuron of hippocampal CA1 region, CA3 region and dentate gyrus of the control group were the lowerest, and those in the FC group were the highest. HO-1 mRNA expression in the neuron of dentate gyrus in the FC group was significantly higher than that in the ZnPP treatment group (P < 0.01), and those in the FNC group and control group was significantly lower than that in the ZnPP treatment group (P < 0.01). CONCLUSION: FC can cause brain injury. Over-expression of HO-1 mRNA and the increase of CO are involved in the patho-physiological process of FC. ZnPP can inhibit HO-1mRNA activity and decrease CO level, which is one of pathways for protecting brain.     

Neuroprotective effect of high-dose hyperbaric oxygenation on rats with acute cerebral infarction in super-early stage

BACKGROUND: Previously, only single short-time low-dose hyperbaric oxygenation (HBO) protocol was administrated to treat acute ischemic stroke in early stage and the conflicting results were obtained. There are few studies to report the outcome of administering long-time (can cover all the natural pathologic progression period) high-dose HBO to treat the disease. OBJECTIVE: To evaluate the therapeutic effect between two kinds of high-dose hyperbaric oxygenation on super-early stage of acute permanent middle cerebral artery occlusion (MCAO) in rats. DESIGN: A randomized controlled experimental study. SETTING: Beijing Tiantan Hospital, Capital Medical University; Beijing Research Institute of Neurosurgery. MATERIALS: Seventy-four male SD rats, aged 2.5 months old, weighing （280±20）g, were provided by the Animal Institute, Chinese Academy of Medical Sciences. Hyperbaric oxygenation device was hyperbaric air cabin in which there was a self-made pure oxygen animal experimental cabin (made in China). METHODS: This experiment was carried out in the municipal laboratory of Beijing Tiantan Hospital affiliated to Capital Medical University and Beijing Research Institute of Neurosurgery. ① Experimental intervention: All the rats were developed into models of permanent MCAO by suture embolism. Then, they were randomly divided into two HBO groups (9 hours and 18 hours) and control group, with 24 rats in each as well as 3-hour ultrastructure control group, with 2 rats. After being modeled for 3 hours, rats in the two HBO groups stayed in the hyperbaric cabin for 9 hours and 18 hours, separately. Rats in the 9-hour HBO group inhaled pure oxygen at hours 1, 3, 5, 7 and 9, and hyperbaric air at hours 2, 4, 6 and 8. Rats in the 18-hour HBO group inhaled pure oxygen at hours 1, 3, 5, 7, 9, 11, 13, 15 and 17, and hyperbaric air at hours 2, 4, 6, 8, 10 12, 14, 16 and 18. After being created into models, rats in the control group and 3-hour ultrastructure control group breathed room air. ② Experimental evaluation: Neurologic functions of rat models in the 9-hour and 18-hour HBO groups as well as control group were scored by Bederson and Garica two neurological grading systems at hours 14 and 28 and on day 5; Infarct volume of rat models in the two HBO groups and control group was measured at hour 24 and on day 5 with NIH image processing software Image J; The pathological changes of brain tissue in the brain infarct region and its opposite region of rat models in the two HBO groups and 3-hour ultrastructure control group were observed with a Philips EM 208S transmission electron microscope. MAIN OUTCOME MEASURES: ① Neurobehavioral outcome. ② Rat brain infarct volume. ③ Ultrastructure of brain tissue in the ischemic penumbra of infarct models at the different time points RESULTS: ① Neurobehavioral outcome: After treatment, Garica score in the 9-hour and 18-hour HBO groups was significantly higher than that in the control group (P < 0.01). Bederson score on day 5 after modeling in the 9-hour and 18-hour HBO groups was significantly lower than that in the control group (P < 0.01). ② Cerebral infarct volume: Cerebral infarct volume in the 9-hour and 18-hour HBO groups was significantly smaller than that in the control group at hour 24 and on day 5 after modeling (P < 0.01). In the 18-hour HBO group, infarct volume on day 5 after modeling was significantly larger than that at hour 24 after modeling (P < 0.05). ③In the 3-hour ultrastructure control group, astrocyte edema and neuron damage around the capillary in the infarct cerebral tissue significantly relieved in the rats which were subjected to HBO. CONCLUSION: High dose of HBO is highly efficient in reducing infarct volume and improving neurobehavioral outcome of rats with acute cerebral infarction, and also has an important role in inhibiting the pathological progression of ischemic brain tissue after cerebral infarction.     

口服免疫耐受治疗颅脑创伤的实验研究

目的 探讨口服免疫耐受对脑损伤的治疗作用.方法 58只兔随机分为对照组、脑脊液引流组、脑脊液引流+口服组和免疫佐剂组.收集第1、3、7、14、21天血清,以ELISA法检测IL-1、IFN-γ、IL-10、TGF-β和ABAb浓度,并进行对比.结果 脯脊液引流组IL-1、IFN-γ、ABAb较对照组降低,IL-10较对照组升高;脑脊液引流+口服纰IL-1、IFN-γ、ABAb较其他组明显降低,而IL-10、TGF-β明显升高;免疫佐剂组介于对照组和脑脊液引流+口服组之间.结论 脑脊液引流对颅腩创伤有治疗作用;口服免疫耐受对颅脑创伤有治疗作用;完全弗氏佐剂部分抑制了口服免疫耐受.

Abstract：

Objective To explore the cerebral protective effects of oral tolerance therapy in rabbit TBI-models established by lateral fluid percussion machine.Method 58 rabbits were divided into four groups randomly( 18 in control group, 15 in CSF drained group, 10 in CSF drained + feed group and 15 in CSF drained + feed + immunologic adjuvant group).Rabbit's CSF were drained and injected into cistern in control group; were drained only in CSF drained group;were drained and feed by mouth in drained + feed group;were drained and injected with 50 μg complete Freud's adjuvant under the skin of posterior foot and rabbits in drained + feed + immunologic adjuvant group.1 ml CSF was drained everyday until a week and phlebotomized and tested with ELISA to observe the changes of IL-1 ,IFN-γ,IL-10,TGF-β and ABAb at the time points of 1 d,3 d,7 d,14 d,21 d in each groups.Results Levels of IL-1,IFN-γ and ABAb in CSF drained group were lower and levels of IL-10 were higher than that in control group;levels of IL-1 ,IFN-γ, ABAb in CSF drained + feed group were lower and levels of IL-10,TGF-β were higher than that in any other groups significantly; levels of IL-1 , IFN-γ, ABAb in CSF drained + feed + immunologic adjuvant were lower than that in control group,while they were higher than that in CSF drained + feed group;levels of IL-10 and TGF-β in CSF drained + feed + immunologic adjuvant group were higher than that in control group,while they were lower than that in CSF drained +feed group.Statistic differences among groups were significant P < 0.05 ).The mortality rate and disability rate of CSF drained + feed group were the lowest, while the cure rate was the highest among four groups.The control group came to be the worst outcome.And the other two groups were in the middle.Conclusions CSF drainage can help to cure traumatic brain injury.CSF drainage and feed by mouth can result in oral tolerance and lighten the injury,so oral tolerance is a useful therapy to treat traumatic brain injury.     

Negative regulation of miRNA-9 on oligodendrocyte lineage gene I during hypoxic-ischemic brain damage

Oligodendrocyte lineage gene 1 plays a key role in hypoxic-ischemic brain damage and myelin repair, miRNA-9 is involved in the occurrence of many related neurological disorders. Bioin- formatics analysis demonstrated that miRNA-9 complementarily, but incompletely, bound oligodendrocyte lineage gene 1, but whether miRNA-9 regulates oligodendrocyte lineage gene 1 remains poorly understood. Whole brain slices of 3-day-old Sprague-Dawley rats were cultured and divided into four groups： control group; oxygen-glucose deprivation group （treatment with 8% O2 ＋ 92% N2 and sugar-free medium for 60 minutes）; transfection control group （after oxygen and glucose deprivation for 60 minutes, transfected with control plasmid） and miRNA-9 transfection group （after oxygen and glucose deprivation for 60 minutes, transfected with miRNA-9 plasmid）. From the third day of transfection, and with increasing culture days, oligodendrocyte lineage gene 1 expression increased in each group, peaked at 14 days, and then decreased at 21 days. Real-time quantitative PCR results, however, demonstrated that oligoden- drocyte lineage gene 1 expression was lower in the miRNA-9 transfection group than that in the transfection control group at 1, 3, 7, 14, 21 and 28 days after transfection. Results suggested that miRNA-9 possibly negatively regulated oligodendrocyte lineage gene 1 in brain tissues during hypoxic-ischemic brain damage.     

标准去骨瓣减压术联合脑脊液循环重建治疗重型颅脑损伤的疗效比较

目的探讨单纯标准去骨瓣减压术与联合脑脊液循环重建术治疗重型颅脑损伤的疗效。方法 72例经同一术者手术的重型颅脑损伤患者分为研究组38例和对照组34例。研究组给予标准去骨瓣减压术联合脑脊液循环重建治疗,对照组予以单纯去骨瓣治疗。对比两组临床疗效。结果研究组与对照组术前临床资料(性别、年龄、致伤原因、GCS评分、Helsinki CT评分及手术时机)无明显差异(P0.05)。研究组手术减压完成时间相对较长(2.8±0.4 h vs.2.5±0.3 h,P0.05);、术后第1天Helsinki CT评分较低[3(2,5)vs.5(2,9),P0.01];术后NICU滞留时间较短(5.54±3.09 d vs.7.24±2.74 d,P0.01);术后7 d内颅内压超过20 mm Hg的累计时间较短(23.2±4.4 h vs 56.8±8.3 h,P0.01);术后3个月GOS评分研究组显著优于对照组,差异有统计学意义(P0.01)。结论相对于传统标准去骨瓣减压术,联合术中脑脊液循环重建治疗重型颅脑损伤的疗效显著提高,值得多中心临床研究进一步研究。     

早期颅骨修补对行去骨瓣减压术的脑损伤及脑出血患者预后的影响研究

目的研究早期颅骨修补对行去骨瓣减压术的脑损伤及脑出血患者的术前术后神经功能缺损评分及并发症的影响。 方法选取深圳市宝安区沙井人民医院神经外科自2016年1月至2018年5月收治的76例行去骨瓣减压术的脑损伤及脑出血患者作为研究对象,采用随机数字表法将入组患者分为早期组（35例）和对照组（41例）,早期组在去骨瓣减压术后4~6周内实施颅骨修补,对照组在术后3~6个月后实施修颅骨修补,对比2组患者术前术后的美国国立卫生研究院卒中量表（NIHSS）评分、术后并发症发生情况以及日常生活能力评分（ADL）和肢体运动功能评分（Fugl-Meyer）。 结果治疗前2组患者的NIHSS评分、ADL评分及Fugl-Meyer评分比较,差异均无统计学意义（P>0.05）。治疗后2组患者的NIHSS评分均显著下降（P<0.05）,且早期组的NIHSS评分显著低于对照组;早期组的ADL评分和Fugl-Meyer评分显著高于对照组（P<0.05）;早期组的并发症发生率显著低于对照组（P<0.05）。 结论颅脑损伤患者实施去骨瓣减压术后,早期实施颅骨修补能够显著改善患者的神经功能缺损状况,并有助于降低术后并发症的发生,对于患者的临床治疗和预后恢复具有积极的影响。     

应急状态下早期去骨瓣减压治疗重型颅脑损伤时间窗的初步研究

目的探讨模拟应急状态下野战医院实施早期去骨瓣减压术（EDC）的可行性和可靠性。 方法单中心回顾性队列研究解放军第九六〇医院神经外科自2016年1月至2019年9月收治的40例重型颅脑损伤（sTBI）患者，按照手术时机的不同将患者分为EDC组和去骨瓣减压术（DC）组，比较2组患者的手术时间窗、术中输血量、伤后24 h内脑挫裂伤进展性发展形成血肿、术后出现脑疝时间窗、术后达到安全后送的生命体征稳定时间窗等指标。 结果EDC组的手术时长短于DC组，术中输血量少于DC组，24 h内进展性脑挫裂、脑疝发生率小于DC组，脑疝发生时间窗长于DC组，差异均有统计学意义（P<0.05）。2组患者的术后生命体征稳定时间比较，差异无统计学意义（P>0.05）。 结论EDC是应急状态下野战医疗所治疗sTBI有效的手术方式。     

大骨瓣减压术治疗颅脑创伤后顽固性高颅压

目的 探讨大骨瓣开颅减压术(DC)治疗重型颅脑创伤(sTBI)后顽固性高颅压的作用及实施DC的时机对预后的影响.方法 回顾性分析132例临床资料,根据伤后6个月时的GOS评分将其分为良好组(GOS 4～5分,n=55),不良组(GOS 2～3分,n=46)和死亡组(GOS 1分,n=31).研究DC对于sTBI患者伤后颅内压(ICP)和脑灌注压(CPP)治疗作用及不同时间实施DC对预后的影响.结果 本研究病例的死亡率为23.5%(31/132),恢复良好率41.7%(55/132).DC前后的ICP平均值为(35.0±12.8)mmHg和(18.3±12.0)mmHg(P＜0.05)、CPP平均值为(50.2±12.4)mmHg和(60.6±12.0)mmHg(P＜0.05),在恢复良好组,DC前后这两个指标变化则更为显著.在伤后不同时间段实施DC与死亡率和恢复良好率无显著相关性.结论 DC对于sTBI后弥漫性脑肿胀、脑水肿所致顽固性高颅压患者在存活组比死亡组更能有效地降低ICP和升高CPP,而伤后实施DC的时间对于预后影响不明显.DC后持续存在ICP≥25 mmHg是预测死亡的敏感指标.

Abstract：

Objective To investigate the role of decompressive craniectomy (DC) to decrease the intractable intracranial hypertension(ICH) due to the diffuse brain swelling and/or cerebral edema after severe traumatic brain injury and the time window of DC to affect on the prognosis.Methods The clinical record of 132 patients who underwent DC for post- traumatic intractable ICH in our hospital from July 2003 to December 2009 with sTBI(Glasgow coma scale≤8) were analyzed retrospectively.The outcome was as measured by Glasgow Outcome Scale (GOS) at the 6th month post-trauma and these patients were divided into favorable group(GOS 4～5,n = 55 ),unfavorable group (GOS 2 ～ 3,n = 46) and Death (GOS 1,n = 31 ).The influence of DC on intracranial pressure (ICP),cerebral perfusion pressure (CPP) and timing of DC on prognosis were analyzed.Methods Of 132 patients,mortality was 23.5% (31/132 ),favorable outcome was observed in 41.7% (55/132 ).Through undergoing DC,ICP decreased from (35.0±12.8) mmHgto (18.3±12.0) mmHg(P＜0.05)and CPP increased from (50.2±12.4)mmHg to (60.6±12.0)mmHg(P＜0.05).These changes were more significant in survivors than in non- survivors (P=0.001 and P=0.003).No tendency towards either increased or decreased in favorable outcome and mortality was found relative to the timing of DC post-trauma.Persistent ICP≥25 mmHg of post- DC was a predicted parameter of mortality(sensitivity 81.6% ,specificity 92.4%,positive predictive value 68.4%,negative predictive value 94.7%).Conclusion DC deceased ICP and increased CPP more obviously in survivors compared to non-survivors in sTBI with ICH.The timing of DC showed no clear trend,for either good neurological outcome or death.The postoperative ICP ≥ 25 mmHg was a threshold to predicted mortality.     

紧急钻颅及顺序硬脑膜剪开术治疗特重型颅脑损伤伴脑疝

目的探讨联合应用紧急钻颅和顺序硬脑膜剪开术治疗特重型颅脑损伤伴颅内血肿、脑挫裂伤及脑疝的效果。方法对21例特重型颅脑损伤伴脑疝的患者行紧急钻颅和标准大骨瓣减压术,术中硬脑膜顺序剪开,逐渐彻底减压(A组)。以标准大骨瓣减压和一次性硬脑膜剪开术治疗的19例同样的颅脑损伤伴脑疝患者作为对照(B组)。结果术中发生急性脑膨出A组5例(23.8%),B组14例(73.7%),两组术中急性脑膨出发生率相差显著(P<0.05)。术中瞳孔恢复正常或缩小A组19例(90.5%),B组8例(42.1%);无变化A组2例,B组11例。A组术中瞳孔恢复正常、缩小率明显高于B组(P<0.01)。术后6个月预后按GOS,A组预后良好或中残15例(71.4%),B组5例(26.3%);A组重残、植物生存和死亡6例(28.6%),B组14例(73.7%)。两组预后良好及中残者的百分比有明显差异(P<0.05)。结论紧急钻颅和顺序硬脑膜剪开逐渐彻底减压的联合应用,在特重型颅脑损伤伴脑疝的抢救中是一种有效的方法,能明显地提高抢救成功率,降低了致残率和死亡率。     

控制性减压术对重度颅脑损伤后脑梗死的防治效果

目的探讨控制性减压术对重度颅脑损伤后脑梗死的防治效果。方法研究对象选取2012-05—2016-03我院诊治的86例重度颅脑损伤患者,以入院先后编号,采用随机简单抽样的方式纳入观察组和对照组,每组43例。观察组给予控制性减压术治疗,对照组给予大骨瓣减压术治疗,术后随访6个月,观察2组术后脑梗死发生率、颅内压、Barthel指数、GOS评分。结果观察组颅内压、脑梗死发生率明显低于对照组,差异有统计学意义(t=5.442,χ2=4.745,P0.05);Barthel指数、GOS评分均显著高于对照组(t=4.882、4.961,P0.05)。结论相比传统标准大骨瓣减压术,控制性减压术治疗重度颅脑损伤效果更佳确切,在减少术后颅内压和脑梗死的同时,利于患者脑功能恢复,提高患者生活自理能力。     

颅脑外伤去骨瓣减压术后继发硬膜下积液的危险因素分析

目的分析颅脑外伤去骨瓣减压术后继发性硬膜下积液的危险因素。方法回顾性分析我院2014年1月至2016年6月间的138例颅脑外伤去骨瓣减压术患者的临床资料和影像学资料。根据术后是否发生硬膜下积液分为积液组和非积液组,通过单因素t检验、卡方检验和多因素Logistic回归分析总结颅脑外伤去骨瓣减压术后发生硬膜下积液的影响因素。结果 138例患者中,85例患者发生硬膜下积液,发生率为61.6%。单因素分析结果显示两组患者在性别、年龄、术前GCS评分、环池受压、术前是否合并脑疝、硬膜外血肿、脑内血肿、脑室内出血、蛛网膜下腔出血、骨瓣的前后径大小、骨瓣的最高径大小、去骨瓣减压的侧别均无统计学意义(p0.05)。去骨瓣减压术后硬膜下积液和中线移位大于5 mm、皮层切开、硬膜下血肿、骨瓣边缘距中线距离小于2 mm有明显关联。多因素分析结果显示只有中线移位大于5 mm和皮层切开是危险因素。结论颅脑外伤去骨瓣减压术后继发性硬膜下积液和中线移位大于5mm、皮层切开有明显关联,应引起重视。     

大骨瓣减压对重型颅脑创伤治疗作用的临床研究

目的 探讨大骨瓣减压术(DC)对重度颅脑损伤(STBI)的治疗价值.方法 纳入132例STBI患者,分两组采用大骨瓣减压术或常规骨瓣开颅,每组各66人.随访6个月,首要结局评价指标为临床疗效,次要结局评价指标为术后并发症的发生.结果 6个月时,大骨瓣减压术组死亡10例(15.2％)、长期昏迷2例(3.0％)、重等残疾13例(19.7％)、中等残疾6例(9.1％)、良好35例(53.0％);常规骨瓣开颅组分别为14例(21.2％)、4例(6.1％)、20例(30.3％)、18例(27.3％)、10例(15.2％).大骨瓣减压术组疗效好于常规骨瓣开颅组(,=37.998,P=0.000).6个月内,大骨瓣减压术组发生急性脑膨出7例(10.6％)、迟发性血肿5例(7.6％)、外伤癫痫6例(9.1％)、颅内感染3例(4.5％)、切口脑脊液漏3例(4.5％),总共并发症24例(36.4％);常规骨瓣开颅组分别为20例(30.3％)、5例(7.6％)、7例(10.6％)、2例(3.0％)、2例(3.0％)和36例(54.5％).大骨瓣减压术组术后并发症少于常规骨瓣开颅组(x2=4.400,P=0.036).经多因素凋整后,大骨瓣减压术疗效良好的机会是常规骨瓣开颅的2.173倍(p=0.011).结论 大骨瓣减压术对重度颅脑损伤的治疗效果优于常规骨瓣开颅,预后好、并发症少.     

阶梯减压下去骨瓣减压术对重度颅脑损伤患者术后转归的影响

目的探讨阶梯减压下去骨瓣减压术对重度颅脑损伤（sTBI）患者术后转归的影响。 方法将吉林大学第一医院二部神经外科自2014年11月至2015年12月收治的行去骨瓣减压术的sTBI患者68例采用随机数字表法分为观察组和对照组各34例。观察组术中全程监测颅内压,采用阶梯减压的方法;对照组行标准外伤大骨瓣减压术。术后1个月采用Baethel指数（BI）评估日常生活能力,采用肢体运动功能运动量表（FM）评估肢体运动功能,比较手术并发症发生率,术后6个月采用GOS评分评估患者近期预后。 结果观察组的恢复良好率（41.18%）明显高于对照组（17.64%）,差异具有统计学意义（P<0.05）;观察组术后1个月BI评分、FM评分（78.37±8.96、83.67±14.72）高于对照组（65.24±7.91、72.33±13.68）,差异具有统计学意义（P<0.05）;观察组急性脑膨出发生率（5.89%）低于对照组（23.53%）,差异具有统计学意义（P<0.05）;术后迟发性颅内血肿、大面积脑梗的几率（8.82%、5.89%）略低于对照组（26.47%、11.76%）,差异无统计学意义（P>0.05）。 结论阶梯减压下去骨瓣减压术可降低sTBI患者急性脑膨出发生率,改善近期预后。