阿魏酸对创伤性脑损伤小鼠的神经保护作用

目的本研究利用创伤性脑损伤(traumatic brain injury,TBI)小鼠模型观察阿魏酸(FA)对TBI的神经保护作用,为防治TBI继发性损伤的药物开发提供新思路。方法利用C57/BL6小鼠采用小鼠重复轻度脑损伤模型进行造模。通过干湿重比值法检测脑组织水肿、水迷宫实验检测小鼠学习记忆能力、HE染色法观察小鼠脑组织形态学变化、采用免疫组化法检测小胶质细胞的激活情况。结果与TBI组小鼠比较,阿魏酸组小鼠:脑含水量明显降低(P<0.05),Morris水迷宫实验中逃避潜伏期较TBI模型组明显缩短,原象限停留时间明显延长,活化的小胶质细胞减少。结论阿魏酸可改善TBI小鼠的空间学习记忆能力,降低TBI小鼠脑含水量,改善TBI小鼠的脑组织形态学变化,其机制与阿魏酸抑制小胶质细胞活化有关。     

Reference Values and Psychometric Properties of the Quality of Life After Traumatic Brain Injury-Overall Scale in Italy,The Netherlands,and the United Kingdom

ObjectivesThe Quality of Life after Brain Injury-Overall Scale (QOLIBRI-OS) is a short screening instrument for assessing disease-specific health-related quality of life (HRQoL) after traumatic brain injury. To date, no reference values are available for the QOLIBRI-OS in general populations. Thus, this study aimed to establish reference values for the QOLIBRI-OS in general population samples from Italy, The Netherlands, and the United Kingdom.MethodsData were collected using an online survey. The total sample comprised 11759 participants, consisting of 3549 Italian, 3564 Dutch, and 4646 British subjects. In this sample, 49% of the total sample did not report any health complaints, whereas 51% had at least 1 chronic health condition. Reference values were deduced for the QOLIBRI-OS for health-condition–related samples and total general population samples per country. To ensure the comparability of these values, measurement invariance was assessed using a multigroup confirmatory factor analysis. Covariates characterizing the reference values were selected with the help of regression analyses.ResultsThe confirmatory factor analysis confirmed that the QOLIBRI-OS scores measured the same traumatic brain injury–specific HRQoL construct across the 3 countries. Healthy individuals reported significantly higher HRQoL than individuals with at least 1 chronic health condition. Older age and higher education levels were significantly associated with higher HRQoL.ConclusionsBecause the reference values displayed differences in terms of age and education level across the 3 countries, we recommend using country-specific reference values stratified by sociodemographic and health status in research and clinical practice.     

大鼠脑损伤后GABA及其受体GABAAR的变化

目的 探讨GABA及其受体GABAAR在创伤性脑损伤（TBI）后的变化规律及其在继发性脑损害中的作用。方法 用大鼠颅脑打击伤动物模型、免疫组织化学方法,观察了致伤后不同时相大鼠伤侧及对侧皮层、海马的GABA及GABAARα2阳性神经元的表达变化。结果 致伤后伤侧皮层GABA／GABAARα1阳性神经元逐渐减少,12h降至最低,对侧皮层无改变;伤侧海马及对侧海马GABA阳性神经元逐渐减少,12h降至最低;伤侧海马GABAARα1的改变与GABA的改变一致,对侧海马无改变。结论 TBI后脑内抑制性神经递质GABA及其受体GABAAR的表达下调也可能是继发性脑损害的重要因素之一。     

The WCST-64: A Standardized Short-Form of the Wisconsin Card Sorting Test

The Wisconsin Cart Sorting Test (WCST) is a well-established measure of executive function. Practical and financial constraints have increased the need for abbreviated neuropsychological procedures. A number of abbreviated versions of the WCST have been introduced and cogent arguments can be made for one over another in certain situations. However, the single deck, 64-card WCST (WCST-64) is the most logical and practical short form. Psychological Assessment Resources (PAR) has recently published a new manual with comprehensive norms for the WCST-64. This paper reviews the new product, discusses the comparability of the WCST-64 and the standard version, and suggests directions for future research.     

Is computer-assisted training effective in improving rehabilitative outcomes after brain injury? A case-control hospital-based study

BackgroundRehabilitation of impaired cognitive functions begins to be considered a standard component of medical care after acquired brain injury. Indeed, many evidences support the effectiveness of the two major categories of techniques, i.e. the traditional and computer-assisted ones, which are widely used in cognitive rehabilitative treatment.ObjectiveAim of this study is to evaluate the effects of pc – cognitive training in brain injury patients.MethodsWe studied 35 subjects (randomly divided into two groups), affected by traumatic or vascular brain injury, having attended from January 2010 to December 2012 the Laboratory of Robotic and Cognitive Rehabilitation of IRCCS Neurolesi of Messina. Cognitive impairment was investigated through psychometric battery, administered before (T0) and two months (T1) after the cognitive pc-training, which was performed only by the experimental group, in addition to conventional treatment. Statistical analysis was performed using Wilcoxon test with a p < 0.01.ResultsAt time T0, all patients showed language deficits and cognitive alterations in visual attention and memory abilities. After the rehabilitation program we noted a global improvement in both the groups. However, at T1, the experimental group showed a greater cognitive improvement than the control group, with significant differences in nearly all the neuropsychological tests performed.ConclusionsOur data suggest that cognitive pc-training may be a promising methodology to optimize the rehabilitation outcomes following brain injury.     

Outcome measures from experimental traumatic brain injury in male rats vary with the complete temporal biomechanical profile of the injury event

Millions suffer a traumatic brain injury (TBI) each year wherein the outcomes associated with injury can vary greatly between individuals. This study postulates that variations in each biomechanical parameter of a head trauma lead to differences in histological and behavioral outcome measures that should be considered collectively in assessing injury. While trauma severity typically scales with the magnitude of injury, much less is known about the effects of rate and duration of the mechanical insult. In this study, a newly developed voice-coil fluid percussion injury system was used to investigate the effects of injury rate and fluid percussion impulse on a collection of post-injury outcomes in male rats. Collectively the data suggest a potential shift in the specificity and progression of neuronal injury and function rather than a general scaling of injury severity. While a faster, shorter fluid percussion first presents as a mild TBI, neuronal loss and some behavioral tasks were similar among the slower and faster fluid percussion injuries. This study concludes that the sequelae of neuronal degeneration and behavioral outcomes are related to the complete temporal profile of the fluid percussion and do not scale only with peak pressure.     

Mechanical stretch induces myelin protein loss in oligodendrocytes by activating Erk1/2 in a calcium-dependent manner

Myelin loss in the brain is a common occurrence in traumatic brain injury (TBI) that results from impact-induced acceleration forces to the head. Fast and abrupt head motions, either resulting from violent blows and/or jolts, cause rapid stretching of the brain tissue, and the long axons within the white matter tracts are especially vulnerable to such mechanical strain. Recent studies have shown that mechanotransduction plays an important role in regulating oligodendrocyte progenitors cell differentiation into oligodendrocytes. However, little is known about the impact of mechanical strain on mature oligodendrocytes and the stability of their associated myelin sheaths. We used an in vitro cellular stretch device to address these questions, as well as characterize a mechanotransduction mechanism that mediates oligodendrocyte responses. Mechanical stretch caused a transient and reversible myelin protein loss in oligodendrocytes. Cell death was not observed. Myelin protein loss was accompanied by an increase in intracellular Ca²⁺ and Erk1/2 activation. Chelating Ca²⁺ or inhibiting Erk1/2 activation was sufficient to block the stretch-induced loss of myelin protein. Further biochemical analyses revealed that the stretch-induced myelin protein loss was mediated by the release of Ca²⁺ from the endoplasmic reticulum (ER) and subsequent Ca²⁺-dependent activation of Erk1/2. Altogether, our findings characterize an Erk1/2-dependent mechanotransduction mechanism in mature oligodendrocytes that de-stabilizes the myelination program.     

Total body irradiation: Significant dose sparing of lung tissue achievable by helical tomotherapy

PurposeTotal body irradiation (TBI) is an important procedure in the conditioning for bone marrow and hematopoietic stem cell transplantation. Doses up to 12 Gy are delivered in hyperfractionated regimes. TBI performed with helical Tomotherapy® (Accuray, Madison, Wisconsin, USA) is an alternative to conventional techniques to deliver dose in extended target volumes with the possibility of simultaneous dose sparing to organs at risk. In this study we focused on maximum dose reduction to the lungs in TBI using helical Tomotherapy®.Material and methodsForty treatment plans of patients who received TBI were calculated with TomoH® (Accuray, Madison, Wisconsin, USA, Version 2.0.4) with a dose of 12 Gy delivered in six equal fractions (2 × 2 Gy/day). Planning iterations necessary to accomplish ICRU 83 report should be less than 250. Treatment time should be practicable in daily routine (<60 min.). Besides the usual contouring of organs at risk special contouring was required for optimization processes which focused on maximum dose sparing in the central lung tissue. Dose constraints (D2, D98, D99) were predefined for target volumes (i.e. PTV TBI D99: 90% of prescribed dose). Homogeneity index <0.15 was defined for acceptability of the treatment plan.ResultsFor all patients acceptable treatment plan fulfilling the predefined constraints were achievable. An average time of 46 min is required for treatment. Thirty-four of forty patients fulfilled D2 in the PTV TBI. Four patients failed D2 due to a high BMI >28 (maximum dose 13.76 Gy = 114.7%). The D98 in the PTV TBI was not reached by 2/40 patients due to BMI > 31 (minimum dose 11.31 Gy = dose coverage of 94.2%). Also these two patients failed the homogeneity index <0.15. The mean lung dose over all patients of the right lung was 7.18 Gy (range 6.4–9.5 Gy). The left lung showed a median (D50) dose of 7.9 Gy (range 6.7–9.3 Gy). Central lung dose showed a mean dose (D50) of 5.16 Gy (range 4.02–7.29 Gy). The D80 of the central lung showed an average dose of 3.87 Gy.ConclusionsTotal body irradiation using helical Tomotherapy® can be delivered with maximum lung tissue sparing (<6 Gy) but without compromise in adjacent PTV TBI structures (i.e. ribs, heart). High conformity and homogeneity in extended radiation volumes can be reached with this technique in an acceptable planning and treatment time. Limitations may occurred in patients with high body mass index.