Energy Metabolic Changes in the Early Post-injury Period Following Traumatic Brain Injury in Rats

Impaired cerebral energy metabolism may be a major contributor to the secondary injury cascade that occurs following traumatic brain injury (TBI). To estimate the cortical energy metabolic state following mild and severe controlled cortical contusion (CCC) TBI in rats, ipsi-and contralateral cortical tissues were frozen in situ at 15 and 40 min post-injury and adenylate (ATP, ADP, AMP) levels were analyzed using high-performance liquid chromatography (HPLC) and the energy charge (EC) was calculated. At 15 min post-injury, mildly brain-injured animals showed a 43% decrease in cortical ATP levels and a 2.4-fold increase in AMP levels (P < 0.05), and there was a significant reduction of the ipsilateral cortical EC when compared to sham-injured animals (P < 0.05). At 40 min post-injury, the ipsilateral adenylate levels and EC had recovered to the values observed in the sham-injury group. In the severe CCC group, there was a 51% decrease in ipsilateral cortical ATP levels and a 5.3-fold increase in AMP levels with a significant reduction of cortical EC at 15 min post-injury (P < 0.05). At 40 min post-injury, a 2.6-fold ipsilateral increase in AMP levels and an 11% and 44% decrease in EC and ATP levels, respectively, remained (P < 0.05). A 37–38% reduction of the total adenylate pool was observed ipsilaterally in both CCC severity groups at the early time-point, and a 19% and 28% decrease remained in the mild and severe CCC groups, respectively, at 40 min post-injury. Significant contralateral ATP and EC changes were only observed in the severe CCC group at 40 min post-injury (P < 0.05). The energy-requiring secondary injury cascades that occur early post-injury do not challenge the brain tissue to the extent of ATP depletion and may provide a window of opportunity for therapeutic intervention.     

经皮电刺激治疗外伤性外周神经损伤40例的效果分析

目的 本文分析使用经皮神经肌肉电刺激治疗外伤性周围神经损伤的临床疗效,探讨经皮电刺激对神经周围微循环的影响.方法 采用丹迪Keypoint型肌电图仪对40例上肢周围神经不全损伤的患者,行经皮神经肌肉电刺激治疗,配合运动疗法.治疗中使用激光多普勒血流仪(LDF)检测电刺激前、后神经周围微循环血流改变情况,并分析电刺激对微循环的影响.同时在治疗前、后行神经电生理检查对比检测,并对不同病程患者治疗后的效果作对比分析.利用以上分析手段观察受损神经功能的恢复情况.结果 40例臂丛神经、正中神经、桡神经、尺神经不全损伤的患者,经2-10个疗程的治疗后,受损神经功能治愈率达63％ (25/40),有效率为90％ (36/40).LDF检测结果显示电刺激后神经周围微循环血流量较刺激前增加23.36％-26.96％,改善受损神经局部微循环,神经肌电检测结果显示较治疗前有明显好转.在不同病程的患者中进行比较,病程越短者,效果越好.结论 经皮神经肌肉电刺激在外伤性周围神经损伤的治疗中,是一种行之有效的方法,可提高受损神经肌肉的兴奋度,促进受损神经局部的血液循环,有利于周围神经的再生.运动疗法的干预,能改善肌萎缩,增强肌协调力,预防关节僵硬,保持关节活动度,最终取得对外伤性周围神经损伤的满意疗效.应用激光多普勒血流成像技术,测得电刺激前、后神经周围微循环出现明显的血流量增加,证实电刺激能改善受损神经局部微循环.     

Changes in autophagy proteins in a rat model of controlled cortical impact induced brain injury

Autophagy has been implicated in several neurodegenerative diseases and recently its role in acute brain injury has received increased interest. In our study, we investigated the profiles of autophagy-linked proteins (MAP-LC3 (Atg8), beclin-1 (Atg6) and the beclin-1-binding protein, bcl-2, following controlled cortical impact injury in rats—a model for moderate-to-severe traumatic brain injury. We observed significant increases in the levels of the processed form of LC3 (LC3-II) in the ipsilateral cortex 2 h to 2 days after injury when compared to sham. Furthermore, the beclin-1/bcl-2 ratio in the ipsilateral cortex was found to have increased from 1 and 2 days after injury. Since both of these changes are established autophagy-enabling events, and, based on these data, we propose that autophagy, plays a role in the manifestation of cell injury following brain trauma.     

切断海马伞对大鼠硬性脑挫伤后运动行为恢复的影响

硬性挫伤运动皮层诱发大鼠偏瘫及其随后的行为代偿是研究中枢神经可塑性的一个理想模型。本工作观察了切断海马伞对脑挫伤后行为恢复的影响。结果表明：与对照组相比,(1)切断海马伞—穹隆通路明显延缓了大鼠运动平衡能力的恢复;(2)切断海马伞—穹隆通路后,银杏类黄酮(FGb)失去了促进脑挫伤后运动平衡能力恢复的作用;(3)原位杂交显示,脑损伤后海马DG(齿状回)和CA3区中生长相关蛋白(GAP—43)mRNA的水平明显提高;(4)FGb促进脑损伤后海马DG和CA3区中的GAP—43mRNA水平的上调。这些信息提示,海马参与脑硬性挫伤后的运动代偿,FGb促进脑损伤后的运动行为的恢复可能与海马相关[动物学报49(2)：211-217,2003]。     

Micromechanical analysis of brain’s diffuse axonal injury

Computational models are important tools which help researchers understand traumatic brain injury (TBI). A mechanistic multi-scale numerical approach is introduced to quantify diffuse axonal injury (DAI), the most important mechanism of TBI, induced by a mechanical insult at micro-scale regions of the white matter or voxels where fiber orientations are the same. Using the mechanical properties of a single axon with a viscoelastic constitutive relation and its functional failure in terms of electrophysiological impairment, a numerical 2D micro-level lattice method is implemented to directly analyze the percentage of injured axons in a voxel containing a bundle of axons all with the same orientation under biaxial stretches. Reference micro-injury maps are then developed with the input parameters based on the principal strain or stretch values and their direction with respect to axons, which provide the percentage of injured axons in the voxel of interest as the output. The methodology is independent of any statistical analyses of the accident data and medical reports to derive probabilistic injury risk curves for DAI. Avoiding a structurally detailed full finite element head model, this study proposes a micro-mechanical approach which considers the anatomical structure of neural axons in the white matter together with their mechanical properties using a numerical lattice method to analyze the brain’s diffuse axonal injury. This work has the potential to help develop safer prevention tools and more effective diagnosis methods for DAI.     

Neuronal calcium signaling via store-operated channels in health and disease

Store-operated calcium entry (SOCE) is the flow of calcium ions (Ca²⁺) into cells in response to the depletion of intracellular Ca²⁺ stores that reside predominantly in the endoplasmic reticulum (ER). The role of SOCE has been relatively well understood for non-excitable cells. It is mediated mostly by the ER Ca²⁺ sensor STIM1 and plasma membrane Ca²⁺ channel Orai1 and serves to sustain Ca²⁺ signaling and refill ER Ca²⁺ stores. In contrast, because of the complexity of Ca²⁺ influx mechanisms that are present in excitable cells, our knowledge about the function of neuronal SOCE (nSOCE) is still nascent. This review summarizes the available data on the molecular components of nSOCE and their relevance to neuronal signaling. We also present evidence of disturbances of nSOCE in neurodegenerative diseases (namely Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease) and traumatic brain injury. The emerging important role of nSOCE in neuronal physiology and pathology makes it a possible clinical target.     

Therapeutic effects of isothiocyanate prodrugs on rheumatoid arthritis

Isothiocyanates 7a and 7b have poor stability and aqueous solubility. To address these problems, prodrugs 8a and 8b were synthesized. Prodrugs 8a and 8b were stable in HEPES buffer at pH 4.4, but released the active compounds 7a and 7b in HEPES buffer at pH 7.4 and in mouse plasma, respectively. Compound 8a and especially compound 8b showed anti-inflammatory effects. Compound 8b demonstrated significant efficacy in animal models of traumatic inflammation, acute inflammation and rheumatoid arthritis. Compound 8b also did not cause appreciable toxicity in mice after 5?weeks at a daily dose of 200?mg/kg.     

滑膜炎颗粒联合玻璃酸钠治疗创伤性膝关节滑膜炎的疗效及对患者血清炎症因子水平的影响

目的:探讨滑膜炎颗粒联合玻璃酸钠治疗创伤性膝关节滑膜炎的疗效及对患者血清炎症因子水平的影响。方法:选取2015年2月～2017年12月期间我院收治的创伤性膝关节滑膜炎患者216例为研究对象。根据随机数字表法将患者分为对照组(n=108)与研究组(n=108)。对照组患者给予玻璃酸钠治疗,研究组则在此基础上联合滑膜炎颗粒进行治疗,两组均治疗5周。比较两组治疗5周后(治疗后)的临床疗效及治疗前后血清白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)水平,采用视觉模拟量表(VAS)评价患者治疗前后膝关节疼痛程度,美国特种外科医院量表(HSS)评价患者治疗前后膝关节功能,同时观察两组治疗期间不良反应发生情况。结果:研究组患者总有效率为92.59%(100/108),高于对照组患者的78.70%(85/108)(P0.05)。两组患者治疗后IL-6、TNF-α以及IL-1β水平均较治疗前降低,且研究组低于对照组(P0.05)。两组患者治疗后VAS评分较治疗前降低,且研究组低于对照组,HSS评分较治疗前升高,且研究组高于对照组(P0.05)。两组患者不良反应发生率对比差异无统计学意义(P0.05)。结论:滑膜炎颗粒联合玻璃酸钠治疗创伤性膝关节滑膜炎安全有效,可显著改善患者血清炎症因子水平以及膝关节功能,并减轻患者疼痛程度,具有一定的临床应用价值。     

炎症因子相关基因在创伤失血性休克中的研究进展

近年来研究认为在创伤失血性休克的发生发展及液体复苏、缺血再关注过程中均伴随着炎症因子的变化,现将与炎症因子密切相关基因环氧化酶-2(COX-2)、核因子κB(NF-κB)、诱导型一氧化氮合酶(iNOS)、高迁移率族蛋白1(HMGB1)、低氧诱导因子1α(HIF1α)、血红素氧合酶-1(HO-1)、寒冷诱导的RNA结合蛋白(CIRBP)在创伤失血性休克中的作用机制方面的研究及进展作一综述,为创伤失血性休克临床救治提供思路。     

The effect of processing of Chlorellavulgaris: K-5 on in vitro and in vivo digestibility in rats

Two experiments were done to clarify whether or not cell rupture is necessary to improve the digestibility of major components of Chlorella vulgaris: K-5. Chlorella was treated with or without high pressure homogenization (1 × 10⁸ N/m² at less than −20°C) after a heating process (100-120°C). Chlorella (air-dry matter) contained 934 g dry matter and 244 g essential amino acids (total)/kg. Chemical composition was hardly altered irrespective of the treatment. In the first experiment, pepsin digestibility of chlorella protein was determined in vitro. The cell rupture by high pressure homogenization caused a small but significant improvement in pepsin digestibility of chlorella protein compared with the control. In the second experiment, total tract apparent digestibilities of chlorella were determined in the rat. Digestibility of chlorella protein was significantly enhanced by high pressure homogenization, but the difference (88.6% vs. 87.4%, P < 0.01) due to treatment was small and similar to that observed in the in vitro experiment. These results suggested that Chlorella strain vulgaris: K-5 may be an efficient protein source even without cell rupture.