依达拉奉对脊髓缺血再灌注损伤后自由基及Oaspase-3表达的影响

目的探讨自由基清除剂依达拉奉对脊髓缺血再灌注损伤后自由基及Caspase-3蛋白表达的影响。方法采用腹主动脉夹闭法将3（）只家兔制作成脊髓缺血再灌注损伤模型,并随机分为2组,用腹腔注射法给予依达拉奉组注射依达拉奉,空白对照组注射生理盐水,共14d,检测家兔血清自由基（MDA、SOD、NO）水平的变化,采用病理及免疫组织化学方法评估脊髓损伤的病理变化以及Caspase-3表达情况,治疗结束后采用Jacobs法对家兔后肢运动功能评分。结果治疗后依达拉奉组家兔血清MDA、SOD、NO水平显著低于对照组,脊髓病理学也进一证实依达拉奉组脊髓损伤程度较对照组轻微,且损伤节段脊髓组织Caspase-3蛋白的表达水平明显低于对照组,依达拉奉组家兔双下肢Jacobs评分也明显高于对照组。结论依达拉奉能明显降低脊髓损伤后自由基水平,抑制Caspase-3蛋白的表达,可能对脊髓缺血再灌注损伤有保护性作用。     

依达拉奉对大鼠脑创伤后神经细胞凋亡信号通路的影响

目的 探讨依达拉奉对脑创伤后神经细胞凋亡信号通路的影响.方法 135只雄性SD大鼠随机分为对照组(25只)、创伤组(60只)和依达拉奉组(50只).Marmarou's法建立SD大鼠弥漫性脑创伤模型;依达拉奉组大鼠伤后即刻经尾静脉注射依达拉奉10 mg/kg,每天1次,共3 d;分别于伤后1 h、6 h、24 h、48h和72 h采用硫代巴比妥酸法检测大脑皮质中丙二醛(MDA)含量;免疫组化法和Western Blot法检测皮质区磷酸化细胞外信号调节激酶(ERK1/2)及细胞色素C(CytC)的表达;原位缺口末端标记法(TUNEL)检测神经细胞凋亡.伤后24 h、48 h、72 h对大鼠综合运动功能进行评定.结果 与对照组比较,创伤组大鼠脑组织MDA水平(6 h、24 h、48 h、72 h)、磷酸化ERK1/2(1 h、6 h、24 h、48 h)和CytC(6 h、24 h、48 h、72 h)表达明显增高,细胞凋亡数(6 h、24 h、48 h、72 h)增多;综合运动能力评分下降(均P＜0.05).与创伤组比较,依达拉奉组大鼠脑组织MDA含量、磷酸化ERK1/2和CytC表达、神经细胞凋亡数下降;大鼠的运动功能评分回升(均P＜0.05).结论 依达拉奉通过清除氧自由基、抑制ERK1/2信号途径活化、减少神经细胞凋亡而发挥对脑创伤的保护作用.     

依达拉奉对急性重型颅脑损伤疗效的临床观察

目的探讨依达拉奉注射液对急性重型颅脑损伤昏迷患者促醒作用以及对预后的影响。方法将60例重型颅脑损伤患者(GCS≤8分)随机分成两组。观察组30例在常规治疗的基础上加用依达拉奉促醒治疗,对照组30例采用常规治疗。两组于伤后6个月按GOS预后评分评定预后,同时比较两组患者的意识好转率。结果观察组恢复良好率(18/30)与对照组(8/30)比较差异有显著性意义(P＜0．05)观察组治疗后1个月清醒24例,而对照组14例,两组清醒率比较差异有显著性意义(P＜0．01)。两组清醒时间比较,观察组为(12．46±6．29)d,对照组为(15．95±7．53)d。结论依达拉奉治疗重型颅脑损伤昏迷患者时不仅能加速清醒,还能促进预后,提高生活质量。     

依达拉奉治疗急性颅脑损伤的初步疗效观察

目的探讨依达拉奉在急性颅脑损伤中的治疗作用。方法对符合入选标准的64例患者随机分组,实验组32例使用依达拉奉,观察安全性和疗效。结果没有观察到与用药有关的不良反应,治疗组复查CT示脑水肿或脑梗塞体积小于对照组(P<0.05)。结论依达拉奉对急性颅脑损伤的继发性脑损害有较好的辅助疗效。     

依达拉奉治疗急性重型颅脑损伤的疗效观察

目的 观察依达拉奉治疗急性重型颅脑损伤的临床疗效、不良反应及预后.方法 将30例急性重型颅脑损伤患者(GCS≤8分)随机分为依达拉奉治疗组(16例)和常规治疗组(14例),观察治疗前后患者的颅内压(ICP)、头部CT(脑水肿)、格拉斯哥昏迷评分(GCS)和格拉斯哥预后评分情况.结果 2组患者治疗14d后,颅内压及脑水肿程度都有所减轻,但依达拉奉治疗组减轻程度好于常规治疗组.治疗14d后依达拉奉治疗组GCS评分显著高于常规治疗组,伤后3个月依达拉奉治疗组GOS评分也显著高于常规治疗组(P均＜0.05).治疗期间未见严重不良反应发生. 结论应用依达拉奉治疗急性重型颅脑损伤有较好的临床疗效,安全性高,值得临床推广使用.     

依达拉奉对大鼠延髓缺血后神经元凋亡微血管密度的影响

目的探索依达拉奉对大鼠延髓缺血后神经元数量及微血管密度的影响。方法将Wistar大鼠分为假手术组、实验组、缺血对照组。其中实验组及缺血对照组分别给予依达拉奉和生理盐水腹腔注射。标本采用单宁酸氯化铁染色、尼氏染色、Tunel染色,对延髓内微血管密度、神经元及凋亡、神经元计数进行观察。结果实验组中神经元、微血管密度(MVD)减少的程度及神经元凋亡数量均低于缺血对照组。结论依达拉奉在大鼠延髓缺血后具有明显保护作用。     

依达拉奉对大鼠局灶性脑缺血再灌注损伤后细胞凋亡及caspase-3蛋白表达的影响

目的 探讨依达拉奉对大鼠局灶性脑缺血再灌注损伤后神经功能损伤、细胞凋亡及caspasc-3蛋白表达的影响.方法 雄性SD大鼠24只采用随机数字表法分为假手术组、脑缺血再灌注组、生理盐水治疗组、依达拉奉治疗组,每组6只.除假手术组外,其余3组均采用大脑中动脉线栓法制作大鼠局灶性脑缺血再灌注损伤模型.依达拉奉治疗组于脑缺血开始时及再灌注后12 h分别腹腔注射依达拉奉3 mg/kg,生理盐水治疗组同时间注射等量生理盐水;假手术组同样过程造模,但不插入尼龙线造成缺血.造模后24 h后进行大鼠神经行为学评分;应用免疫组织化学及Western blot检测caspase-3蛋白表达水平的变化;利用原位缺口末端标记法(TUNEL法)研究神经细胞凋亡的变化.结果 与脑缺血再灌注组及生理盐水治疗组相比,依达拉奉治疗组大鼠神经行为学评分明显减少,caspase-3免疫阳性细胞及蛋白表达明显减少,凋亡细胞也减少,差异均有统计学意义(P<0.05).结论 依达拉奉能有效减轻脑缺血灌注损伤后神经细胞凋亡.改善神经功能缺损症状,推测其机制与抑制caspase-3蛋白表达有关.     

依达拉奉对急性脑梗死再灌注损伤保护临床分析

目的探讨依达拉奉对急性脑梗死再灌注损伤保护。方法选取我院2006-01～2009-12收治的312例急性脑梗死患者随机分为治疗组162例,对照组150例。对照组组采用:基础治疗,治疗组基础治疗加用依达拉奉治疗,观察神经功能缺损评分变化及临床疗效。结果治疗组和对照组2组治疗5 d、15 d后神经功能缺损程度评分比较P0.05有显著的差异性。2组临床疗效比较,显效率、总有效率P0.05有显著差异性。结论依达拉奉是一种强效的羟自由基清除剂及抗氧化剂,能够有效的对脑缺血再灌注损伤起到保护作用,防止再灌注损伤,减少脑细胞凋亡,减轻临床症状,促进疾病康复。     

依达拉奉治疗脊髓损伤的临床研究

目的 观察依达拉奉对脊髓损伤的疗效.方法 67例脊髓损伤患者分为治疗组和对照组,对照组采用常规治疗,治疗组在常规治疗基础上加用依达拉奉注射液静滴,观察临床疗效.结果 治疗组33例有32例取得Frankel1～3级的改善,平均改善2.0级,1例A级无变化.对照组34例有31例Frankel1～3级改善,平均改善1.4级,恢复到E级10例,远少于治疗组18例.总体而言,在感觉恢复、日常生活活动能力、膀胱功能上,治疗组自身治疗前后及治疗组与对照组治疗后比较无明显改善.结论 依达拉奉注射液治疗脊髓损伤有一定效果,对脊髓损伤细胞具有保护作用,能促进脊髓损伤神经功能的恢复.     

大鼠颅脑损伤后一氧化氮合酶和内皮素的变化及依达拉奉对其的影响

目的观察大鼠颅脑损伤后脑组织中一氧化氮合酶（NOS）和内皮素（ET）含量的变化及依达拉奉对其的影响，并探讨其作用机制。方法将45只SD大鼠随机分为3组，其中正常组5只，麻醉后只行开颅手术，不作头颅打击；治疗组和对照组各20只，采用骨窗形成后硬膜外打击法造成鼠脑挫裂伤模型，治疗组致伤后即刻腹腔内注射5mg／kg依达拉奉，对照组则即刻腹腔内注射等量生理盐水。正常组在伤后1h，对照组和治疗组大鼠分别在伤后1h、6h、12h、24h断头取脑，对大鼠脑外伤后脑组织中NOS和ET含量进行检测。结果（1）治疗组和对照组大鼠脑皮质中的NOS活性在伤后1h较正常组显著升高（P〈0．01），6h开始下降，12～24h降至基础水平。治疗组在伤后1h、6hNOS活性较对照组显著降低（均P〈0.05）。（2）治疗组和对照组大鼠脑皮质中的ET在伤后1-24h较正常组显著升高（P〈0．01）。治疗组在伤后1～24hET较对照组显著降低（ P〈0．05）。结论颅脑损伤后受损脑组织中NOS和ET升高，依达拉奉可通过抑制损伤后NOS和ET起到保护创伤神经元的作用。     

Expression of CAPON after Spinal Cord Injury in Rats

The adaptor protein, carboxy-terminal PDZ ligand of nNOS (CAPON), regulates the distribution of neuronal nitric oxide synthase (nNOS) that increased after spinal cord injury (SCI) and produces the key signaling molecule nitric oxide (NO). But little is known about the role of CAPON in the pathological process of SCI. The main objective of the present study was to investigate expression of CAPON and nNOS in a spinal cord contusion model in adult rats. Real time-polymerase chain reaction (PCR) and Western blot analysis revealed that mRNA and protein for CAPON increased at 2 h after SCI and reached the peak at 8 h, gradually recovered to the baseline level at 14 days. The expression of nNOS mRNA and protein was similar to that of CAPON. During the peak expression, CAPON mRNA was found in the ventral horn, mediate zone, dorsal horn, and white matter by in situ hybridization. Immunofluorescence showed that CAPON was colocalized with nNOS in neurons, oligodendrocytes, and some astrocytes of spinal cord tissues within 5 mm from the epicenter. Interaction between CAPON and nNOS was also detected by co-immunoprecipitation. Thus, the transient expression of high levels of CAPON may provide new insight into the secondary response after SCI. Chun Cheng and Xin Li contributed equally to this work.     

Emerging Concepts in Myeloid Cell Biology after Spinal Cord Injury

Traumatic spinal cord injury (SCI) affects the activation, migration, and function of microglia, neutrophils and monocyte/macrophages. Because these myeloid cells can positively and negatively affect survival of neurons and glia, they are among the most commonly studied immune cells. However, the mechanisms that regulate myeloid cell activation and recruitment after SCI have not been adequately defined. In general, the dynamics and composition of myeloid cell recruitment to the injured spinal cord are consistent between mammalian species; only the onset, duration, and magnitude of the response vary. Emerging data, mostly from rat and mouse SCI models, indicate that resident and recruited myeloid cells are derived from multiple sources, including the yolk sac during development and the bone marrow and spleen in adulthood. After SCI, a complex array of chemokines and cytokines regulate myelopoiesis and intraspinal trafficking of myeloid cells. As these cells accumulate in the injured spinal cord, the collective actions of diverse cues in the lesion environment help to create an inflammatory response marked by tremendous phenotypic and functional heterogeneity. Indeed, it is difficult to attribute specific reparative or injurious functions to one or more myeloid cells because of convergence of cell function and difficulties in using specific molecular markers to distinguish between subsets of myeloid cell populations. Here we review each of these concepts and include a discussion of future challenges that will need to be overcome to develop newer and improved immune modulatory therapies for the injured brain or spinal cord.     

Temporal and Spatial Expression of KIF3B after Acute Spinal Cord Injury in Adult Rats

The KIF3 subunit KIF3B was proved to be associated with mitosis. It has been known to be engaged in intracellular transport of neurons. To elucidate the certain expression and biological function in central nervous system, we performed an acute spinal cord contusion injury model in adult rats. Western blot analysis indicated a marked upregulation of KIF3B after spinal cord injury (SCI). Immunohistochemistry revealed wide distribution of KIF3B in spinal cord, including neurons and glial cells. Double immunofluorescent staining for proliferating cell nuclear antigen and phenotype-specific markers showed increases of KIF3B expression in proliferating microglia and astrocytes. Our data suggest that KIF3B may be implicated in the proliferation of microglia and astrocytes after SCI.     

High-dose Ambroxol Reduces Pulmonary Complications in Patients with Acute Cervical Spinal Cord Injury After Surgery

Background  

Ambroxol has a very high affinity for lung tissues; its concentration is approximately 20 times higher in the lung than in the serum. We aimed to evaluate the effectiveness of high-dose ambroxol (990 mg/day) in the improvement of oxygenation and prevention of postoperative respiratory complications in the patients with acute cervical spinal cord injury (CSCI).     

Acute Hydrocephalus Following Cervical Spinal Cord Injury

We present a case of acute hydrocephalus secondary to cervical spinal cord injury in a patient with diffuse ossification of the posterior longitudinal ligament (OPLL). A 75-year-old male patient visited the emergency department with tetraparesis and spinal shock. Imaging studies showed cervical spinal cord injury with hemorrhage and diffuse OPLL from C1 to C4. We performed decompressive laminectomy and occipitocervical fusion. Two days after surgery, his mental status had deteriorated to drowsiness with dilatation of the right pupil. Findings on brain computed tomography revealed acute hydrocephalus and subarachnoid hemorrhage in the cerebellomedullary cistern, therefore, extraventricular drainage was performed immediately. Acute hydrocephalus as a complication of cervical spine trauma is rare, however, it should be considered if the patient shows deterioration of neurologic symptoms.     

Antioxidant Therapies for Acute Spinal Cord Injury

One of the most investigated molecular mechanisms involved in the secondary pathophysiology of acute spinal cord injury (SCI) is free radical-induced, iron-catalyzed lipid peroxidation (LP) and protein oxidative/nitrative damage to spinal neurons, glia, and microvascular cells. The reactive nitrogen species peroxynitrite and its highly reactive free radicals are key initiators of LP and protein nitration in the injured spinal cord, the biochemistry, and pathophysiology of which are first of all reviewed in this article. This is followed by a presentation of the antioxidant mechanistic approaches and pharmacological compounds that have been shown to have neuroprotective properties in preclinical SCI models. Two of these, which act by inhibition of LP, are high-dose treatment with the glucocorticoid steroid methylprednisolone (MP) and the nonglucocorticoid 21-aminosteroid tirilazad, have been demonstrated in the multicenter NASCIS clinical trials to produce at least a modest improvement in neurological recovery when administered within the first 8 hours after SCI. Although these results have provided considerable validation of oxidative damage as a clinically practical neuroprotective target, there is a need for the discovery of safer and more effective antioxidant compounds for acute SCI.     

Hypothermic Treatment for Acute Spinal Cord Injury

Spinal cord injury (SCI) is a devastating condition that affects approximately 11,000 patients each year in the United States. Although a significant amount of research has been conducted to clarify the pathophysiology of SCI, there are limited therapeutic interventions that are currently available in the clinic. Moderate hypothermia has been used in a variety of experimental and clinical situations to target several neurological disorders, including traumatic brain and SCI. Recent studies using clinically relevant animal models of SCI have reported the efficacy of therapeutic hypothermia (TH) in terms of promoting long-term behavioral improvement and reducing histopathological damage. In addition, several clinical studies have demonstrated encouraging evidence for the use of TH in patients with a severe cervical spinal cord injury. Moderate hypothermia (33°C) introduced systemically by intravascular cooling strategies appears to be safe and provides some improvement of long-term recovery of function. TH remains an experimental clinical approach and randomized multicenter trials are needed to critically evaluate this potentially exciting therapeutic intervention targeting this patient population.