53例重型颅脑损伤长期昏迷病人的催醒效果

目的 介绍53例重型颅脑损伤持续昏迷1个月以上病人的催醒效果和影响催醒效果的因素。方法 伤后昏迷时间1～12个月、GCS≤8分的重型颅脑损伤病人53例，采用高压氧、理疗、药物等综合催醒方法治疗。结果 53例长期昏迷病人中，28例苏醒(52．8％)。按照GOS评分，28例清醒病人中仅6例恢复良好和中残(21．4％)，其他22例病人为重残、无自主生活能力(78．6％)。苏醒成功率与病人是否有原发性脑干伤、脑疝、GCS评分、年龄等冈素有关。结论 采用综合催醒方法，能提高长期昏迷病人苏醒成功率，但神绛功能恢复仍十分闲难。     

Regional cerebral blood flow deficits in mild Alzheimer's disease using high resolution single photon emission computerized tomography

In spite of its wide availability, single photon emission computerized tomography (SPECT) scanning is uncommonly used in the assessment of Alzheimer's disease (AD) and related dementias. In light of recent advances in scanning protocols and image analysis, SPECT needs to be re-examined as a tool in the diagnosis of dementia. A total of 18 subjects with early AD and 10 healthy elderly control subjects were examined with high resolution SPECT during the performance of a simple word discrimination task. SPECT images were coregistered with individual magnetic resonance imaging scans, allowing delineation of predetermined neuroanatomical Regions of Interest (ROI). There was a gradation of regional cerebral blood flow (rCBF) values in both groups, with the lowest values being in the hippocampus and the highest in the striatum, thalamus and cerebellum. Compared to healthy controls, AD subjects demonstrated lower relative rCBF in parietal and prefrontal cortices. Analysis of individual ROI demonstrated bilateral reduction of rCBF in prefrontal poles, posterior temporal and anterior parietal cortex, and unilateral reduction of rCBF in left dorsolateral prefrontal cortex, right posterior parietal cortex and the left cingulate body. There were no significant differences for hippocampal, occipital or basal ganglia rCBF. Discriminant function analysis indicated that rCBF in the prefrontal polar regions achieved the best classification of cases. SPECT has utility in the diagnostic assessment of AD if standardized and semiquantitative techniques are used.     

乏氧组织显像剂单光子计算机断层扫描检测脑出血灶周围乏氧组织的初步研究

目的探讨乏氧组织显像剂(99Tcm-HL-91)单光子计算机断层扫描(SPECT)检测脑出血灶周围乏氧组织的应用价值。方法应用HL-91SPECT脑显像对26例脑出血患者进行检测,并与CT影像学结果及5名健康对照者进行比较。结果26例脑出血患者中17例(65.38%)乏氧显像阳性,乏氧显像阳性区与CT上脑出血灶密切相关;9例阴性者中,6例为小量脑出血患者,包括2例出血量<10ml的小脑出血和丘脑出血,4例出血量<15ml的基底节区和脑叶出血者,另3例为起病后20d检查者。对照组全部阴性。结论HL-91SPECT脑乏氧显像完全适用于脑出血后乏氧组织的临床观察。HL-91SPECT检测所显示出的乏氧区与CT上的脑出血灶的密切相关。     

Iodine-123 labeled reboxetine analogues for imaging of noradrenaline transporter in brain using single photon emission computed tomography

Preliminary investigation of the radioiodinated (S,S)‐reboxetine analogue, ¹²³I‐INER, in baboons showed this tracer to have promise for imaging the noradrenaline transporter (NAT) using single photon emission computed tomography (SPECT). More recently, the radioiodinated (R,S)‐stereoisomer of ¹²³I‐INER, ¹²³I‐NKJ64, has been synthesized and preliminary evaluation in rats has been reported. This article reports the brain distribution and pharmacokinetic properties of ¹²³I‐NKJ64 in baboons and compares results with ¹²³I‐INER data in the same species. SPECT studies were conducted in two ovariectomized adult female baboons using two different protocols: (1) bolus of ¹²³I‐INER or ¹²³I‐NKJ64; and (2) bolus plus constant infusion of ¹²³I‐NKJ64 with reboxetine (2.0 mg/kg) administration at equilibrium. Following bolus injection, both radiotracers rapidly and avidly entered the baboon brain. The regional brain accumulation of ¹²³I‐NKJ64 did not match the known distribution of NAT in baboon brain, contrasting with previous results obtained in rats. Conversely, the regional distribution of ¹²³I‐INER was consistent with known distribution of NAT in baboon brain. No displacement of ¹²³I‐NKJ64 was observed following administration of reboxetine. This contrasts with previous data obtained for ¹²³I‐INER, where 60% of specific binding was displaced by a lower dose of reboxetine. These data suggest that ¹²³I‐NKJ64 may lack affinity and selectivity for NAT in baboon brain and ¹²³I‐INER is the most promising iodinated reboxetine analogue developed to date for in vivo imaging of NAT in brain using SPECT. This study highlights the importance of species differences during radiotracer development and the stereochemical configuration of analogues of reboxetine in vivo. Synapse 66:923–930, 2012. © 2012 Wiley Periodicals, Inc.     

VEGF-165基因对创伤性脑损伤脑血流动力学影响的实验研究

目的 研究外源性血管内皮细胞生长因子(VEGF)基因治疗大鼠创伤性脑损伤(TBI)后脑灌注的变化,了解其血流动力学改变.方法 创伤性脑损伤大鼠模型建立后随机分为3组:治疗组,质粒对照组,外伤组.通过RT-PCR检测脑伤后1h、6h、24h、3d、7d、14 d VEGF mRNA在损伤局部的表达改变;应用CT灌注像(CTP)研究不同时间脑血流量(CBF)、脑血容量(CBV)等参数在VEGF-165基因治疗前后的动态变化.结果 VEGF-165基因治疗创伤性脑损伤大鼠后经RT-PCR扩增的VEGF mRNA绝对积分光密度值水平显著高于外伤组和质粒对照组(P＜0.05).CTP参数和伪彩图均显示基因治疗组脑灌注在伤后24h CBF、CBV有增高趋势,伤后3d、7d脑灌注明显高于TBI 组(P＜0.05),虽然伤后14 d CBF、CBV开始降低,但和TBI组比较仍然较高.结论 本研究结果显示大鼠创伤性脑损伤后外源性VEGF基因能够提高脑损伤组织的脑灌注,改善脑损伤部位微循环,为损伤组织的恢复提供基础.     

Cerebral blood flow changes in general paresis following penicillin treatment: a longitudinal single photon emission computed tomography study

Three cases of general paresis were successfully treated with high-dose penicillin. In all cases, cerebrospinal fluid cell counts decreased to normal and mental status improved rapidly. Cerebrospinal fluid protein concentrations decreased and IQ scores and overall levels of functioning improved gradually over 1 year. Regional cerebral blood flow (CBF) changes were analyzed longitudinally for 1 year using single photon emission computed tomography (SPECT). Autoradiography method and region of interest (ROI) analyses were used for quantitative CBF assessment and 3D stereotactic surface projections (3D-SSP) analyses were used for qualitative CBF pattern assessment. 3D-SSP could not reveal remarkable CBF pattern changes through the courses. The ROI analyses showed remarkable CBF decreases in all brain regions 1 month after the treatment, which recovered to normal levels 1 year after the treatment. These results suggest that remarkable decreases of quantitative CBF counts reflect the disappearance of encephalitis, while their gradual recovery reflects the gradual improvement of cerebral functional activity. As Treponema pallidum infection affects whole brain and CBF changes globally, quantitative CBF assessment may be more efficient than qualitative CBF pattern analyses for the purpose of understanding the pathophysiology of general paresis.     

红花黄色素治疗颅脑损伤作用机制的生物信息学分析

目的 应用生物信息学方法分析红花黄色素（YS）治疗颅脑损伤（TBI）的作用机制。方法 通过GEO数据库查询检索基因表达微阵列芯片数据集GSE21854,筛选差异表达基因（DEGs）, 并与YS靶点基因互相印射取交集。采用DAVID/String数据库对共同靶基因进行GO分析和KEGG通路分析,构建PPI网络。结果 筛选出140个DEGs,与YS靶点基因互相印射后得到26个共同靶基因;进一步GO分析前5个基因功能富集为信号转导、DNA 转录调节、血小板活化、信号与聚集、免疫系统及转录调控区 DNA 结合,KEGG通路途径分析筛选出前5条信号通路包括MAPK信号通路、趋化因子信号通路、PI3K/AKT信号通路、EGFR1信号通路和肿瘤信号通路。PPI分析筛选发现节点最高的中心蛋白编码基因是MAPK3。结论 应用生物信息学方法,可有效获取YS治疗TBI靶向基因的生物学功能、相关信号通路及核心关键蛋白,为后续研究和临床治疗提供了依据。     

Change in cerebral autoregulation as a function of time in children after severe traumatic brain injury: a case series

Objective The objective of this study was to describe changes in cerebral autoregulation after severe pediatric traumatic brain injury (TBI). Materials and methods Two cerebral autoregulation tests were performed during the first 10 days after severe TBI in children <16 years. Cerebral autoregulation was quantified using the mean autoregulatory index (mARI). Results Nine (five males/four females) children (10 ± 5 years) with severe (admission Glasgow Coma Scale (GCS), 5 ± 2) TBI were enrolled. Thirty (3/9) percent of initial exams revealed impaired cerebral autoregulation; all three had returned to intact cerebral autoregulation on second exam. However, in three of nine (33%) patients, cerebral autoregulation worsened on second exam. Of the factors examined, worsening mARI on second exam was associated with worsening head computed tomography (CT) lesion. Conclusions Cerebral autoregulation often changed and worsened during the first 9 days after severe pediatric TBI. Worsening cerebral autoregulation may mirror worsening TBI.     

大鼠脑缺血再灌注损伤后皮层Homerla蛋白改变及意义

目的探讨大鼠脑血再灌注损伤后皮层组织Homerla蛋白的表达改变及其意义。方法选择成年雄性SD大鼠59只,随机分为正常对照组、缺血再灌注损伤后10rain、1h、3h、6h、12h、24h、48h及72h共9组,每组6只。免疫组化染色法和Western blot法测定Homerla蛋白含量,T-PCR法测定HomerlaRNA表达。结果在实验过程中5只动物死亡,54只进入结果分析。与对照组比较缺血再灌注损伤后Homerla蛋白和mRNA灰度值表达出现3个峰值,分别在10min、6h和24h,但在72h仍维持较高水平;与对照组Homerla蛋白免疫评分相比,缺血再灌注损伤后出现两个峰值,分别在6h和24h;Homerla蛋白除神经元外,在胶质细胞也表达。结论在缺血再灌注损伤后,Homerla出现3个表达高峰,可能在不同的机制的影响下对脑损伤发生发展起重要作用。     

Quantification of Tc-99m-ethyl cysteinate dimer brain single photon emission computed tomography images using statistical probabilistic brain atlas in depressive end-stage renal disease patients:Correlation with disease severity and symptom factors

This study adapted a statistical probabilistic anatomical map of the brain for single photon emission computed tomography images of depressive end-stage renal disease patients. This research aimed to investigate the relationship between symptom clusters, disease severity, and cerebral blood flow. Twenty-seven patients (16 males, 11 females) with stages 4 and 5 end-stage renal disease were enrolled, along with 25 healthy controls. All patients underwent depressive mood assessment and brain single photon emission computed tomography. The statistical probabilistic anatomical map images were used to calculate the brain single photon emission computed tomography counts. Asymmetric index was acquired and Pearson correlation analysis was performed to analyze the correlation between symptom factors, severity, and regional cerebral blood flow. The depression factors of the Hamilton Depression Rating Scale showed a negative correlation with cerebral blood flow in the left amygdale. The insomnia factor showed negative correlations with cerebral blood flow in the left amygdala, right superior frontal gyrus, right middle frontal gyrus, and left middle frontal gyrus. The anxiety factor showed a positive correlation with cerebral glucose metabolism in the cerebellar vermis and a negative correlation with cerebral glucose metabolism in the left globus pallidus, right inferior frontal gyrus, both temporal poles, and left parahippocampus. The overall depression severity (total scores of Hamilton Depression Rating Scale) was negatively correlated with the statistical probabilistic anatomical map results in the left amygdala and right inferior frontal gyrus. In conclusion, our results demonstrated that the disease severity and extent of cerebral blood flow quantified by a probabilistic brain atlas was related to various brain areas in terms of the overall severity and symptom factors in end-stage renal disease patients.     

Altered protein markers related to neural plasticity and motor function following electro-acupuncture treatment in a rat model of ischemic-hypoxic brain injury *☆

BACKGROUND：Previous studies have demonstrated that acupuncture treatment could ameliorate impaired motor function,and these positive effects might be due to neural plasticity.OBJECTIVE：Myelin basic protein（MBP）,microtubule-associated protein 2（MAP2）,growth-associated protein-43（GAP-43）,and synaptophysin（SYN） were selected as markers of neural remodeling,and expression of these markers was evaluated with regard to altered motor function following brain injury and acupuncture treatment.DESIGN,TIME AND SETTING：A completely randomized experiment was performed at the Central Laboratory of Peking University First Hospital from November 2006 to May 2007.MATERIALS：Twenty-four Sprague Dawley rat pups,aged 7 days,were selected for the present experiment.The left common carotid artery was ligated to establish a rat model of ischemic-hypoxic brain injury.METHODS：All animals were randomly divided into three groups：sham operation,model,and electro-acupuncture treatment,with 8 rats in each group.Rats in the model and electro-acupuncture treatment group underwent establishment of ischemic-hypoxic brain injury.Upon model established,rats underwent hypobaric oxygen intervention for 24 hours.Only the left common carotid artery was exposed in rats of the sham operation group,without model establishment or oxygen intervention.The rats in the electro-acupuncture treatment group were treated with electro-acupuncture.One acupuncture needle electrode was inserted into the subcutaneous layer at the Baihui and Dazhui acupoint.The stimulation condition of the electro-acupuncture simulator was set to an amplitude-modulated wave of 0-100% and alternative frequency of 100 cycles/second,as well as frequency-modulated wave of 2-100 Hz and an alternative frequency of 3 cycles/second.Maximal current through the two electrodes was limited to 3-5 mA.The stimulation lasted for 30 minutes per day for 2 weeks.Rats in the sham operation and model groups were not treated with electro-acupuncture,but only fixed to the table for     

Altered protein markers related to neural plasticity and motor function following electro-acupuncture treatment in a rat model of ischemic-hypoxic brain injury

BACKGROUND:Previous studies have demonstrated that acupuncture treatment could ameliorate impaired motor function,and these positive effects might be due to neural plasticity.OBJECTIVE:Myelin basic protein(MBP),microtubule-associated protein 2(MAP2),growth-associated protein-43(GAP-43),and synaptophysin(SYN) were selected as markers of neural remodeling,and expression of these markers was evaluated with regard to altered motor function following brain injury and acupuncture treatment.DESIGN,TIME AND SETTING...     

Long-term histological outcome after post-hypoxic treatment with 100% or 40% oxygen in a model of perinatal hypoxic–ischemic brain injury

Hypoxic newborns have traditionally been given supplemental oxygen, and until recently, guidelines for neonatal resuscitation recommended that 100% oxygen be used. Exposure to 100% oxygen after hypoxic injury, however, may exacerbate oxidative stress. The current study evaluated the effect of exposure to 100, 40 or 21% oxygen after neonatal hypoxic–ischemic injury on the severity of brain injury after long-term survival. The severity of histological brain injury was not different in animals exposed to 100% oxygen versus room air. Male animals treated with 40% oxygen post-hypoxia had the lowest mean total histology scores, but this was not statistically significant due to the large variation in injury within each treatment group.These results support the growing number of studies in human infants and experimental animals that show no benefit of 100% oxygen over room air for neonatal resuscitation. Our results suggest that post-hypoxia treatment with 40% oxygen may be beneficial, particularly in males. Further studies of the effects of different concentrations of oxygen on brain injury are warranted and should have sufficient power to examine sex differences.     

Cognitive and psychological flexibility after a traumatic brain injury and the implications for treatment in acceptance-based therapies: A conceptual review

This paper provides a selective review of cognitive and psychological flexibility in the context of treatment for psychological distress after traumatic brain injury, with a focus on acceptance-based therapies. Cognitive flexibility is a component of executive function that is referred to mostly in the context of neuropsychological research and practice. Psychological flexibility, from a clinical psychology perspective, is linked to health and well-being and is an identified treatment outcome for therapies such as acceptance and commitment therapy (ACT). There are a number of overlaps between the constructs. They both manifest in the ability to change behaviour (either a thought or an action) in response to environmental change, with similarities in neural substrate and mental processes. Impairments in both show a strong association with psychopathology. People with a traumatic brain injury (TBI) often suffer impairments in their cognitive flexibility as a result of damage to areas controlling executive processes but have a positive response to therapies that promote psychological flexibility. Overall, psychological flexibility appears a more overarching construct and cognitive flexibility may be a subcomponent of it but not necessarily a pre-requisite. Further research into therapies which claim to improve psychological flexibility, such as ACT, needs to be undertaken in TBI populations in order to clarify its utility in this group.     

Trends in epidemiological and clinical characteristics in severe traumatic brain injury: Analysis of the past 25 years of a single centre data base

ObjectiveTo describe the demographic and clinical profiles of a cohort of environmentally representative severe traumatic brain injury (TBI) cases collected for the past 25 years and to analyse the changes that occurred by dividing the analysis period into 3 equal time periods.Material and methodsThis was an observational cohort study of consecutive adult patients (>14 years of age) with severe closed TBI (Glasgow Coma Scale score [GCS] ≤ 8) who were admitted during the first 48 h after injury to the 12 de Octubre hospital from 1987 to 2012. The most relevant epidemiological and clinical variables reported in the literature were defined and compared in 3 equal time periods (1987–1995, 1996–2004 and 2005–2014).ResultsThere was a 13% reduction in the frequency of severe TBI from the first to the last time period. An increase in the mean age from 35 to 43 years was observed, whereas the frequency of severe TBI according to sex remained approximately the same during the last decades of life. A distinct change was observed in the injury mechanism; traffic accidents decreased from 76% to 55%, particularly those involving 4-wheeled vehicles. However, falls increased significantly, especially in older women, and contusion and subdural haematoma were the most frequent structural injuries. Motor scores could not be reliably assessed for the last time period because of early intubation and sedative drug use.ConclusionsTBI epidemiology in Western countries has changed. This trend was also observed in our environment as an increase in mean age, which reflected the increase in falls among elderly patients.     

High occupancy of sigma-1 receptors in the human brain after single oral administration of fluvoxamine: a positron emission tomography study using [11C]SA4503.

BACKGROUND: Sigma-1 receptors might be implicated in the pathophysiology of psychiatric diseases, as well as in the mechanisms of action of some selective serotonin reuptake inhibitors (SSRIs). Among the several SSRIs, fluvoxamine has the highest affinity for sigma-1 receptors (Ki = 36 nM), whereas paroxetine shows low affinity (Ki = 1893 nM). The present study was undertaken to examine whether fluvoxamine binds to sigma-1 receptors in living human brain. METHODS: A dynamic positron emission tomography (PET) data acquisition using the selective sigma-1 receptor ligand [(11)C]SA4503 was performed with arterial blood sampling to evaluate quantitatively the binding of [(11)C]SA4503 to sigma-1 receptors in 15 healthy male volunteers. Each subject had two PET scans before and after randomly receiving a single dose of either fluvoxamine (50, 100, 150, or 200 mg) or paroxetine (20 mg). The binding potential of [(11)C]SA4503 in 9 regions of the brain was calculated by a 2-tissue 3-compartment model. In addition, we examined the effects of functional polymorphisms of the sigma-1 receptor (SIGMAR1) gene on the binding potential of [(11)C]SA4503. RESULTS: Fluvoxamine bound to sigma-1 receptors in all brain regions in a dose-dependent manner, whereas paroxetine did not bind to sigma-1 receptors. However, there was no association between the SIGMAR1 gene polymorphism GC-241-240TT and binding potential. CONCLUSIONS: The study demonstrated that fluvoxamine bound to sigma-1 receptors in living human brain at therapeutic doses. These findings suggest that sigma-1 receptors may play an important role in the mechanism of action of fluvoxamine.