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1头颈部体表亚低温对危重型颅脑损伤患者神经元特异性烯醇化酶、谷氨酸及预后的影响显示文摘目的观察头颈部体表亚低温(HNC)对危重型颅脑损伤(cTBI)患者神经元特异性烯醇化酶(NSE)、谷氨酸及预后的影响。方法前瞻性分析2016年12月到2020年10月入住3个医院ICU cTBI患者81例,按随机数表分入头颈联合降温组(HNC组41例)和传统冰帽组(HC组40例),在到达医院、入院24 h及72 h检测血NSE和谷氨酸浓度(Glu),全程监测格拉斯哥评分、耳蜗温度、凝血功能、血压、心率变化及寒战反应和28 d病死率,随访6个月格拉斯哥预后评分(GOS),根据28 d预后将患者分为死亡和存活亚组。结果HNC 72 h NSE(56.8±34.0)ng/mL比24 h下降(12.45±18.16)ng/mL,差异具有统计学意义(t=4.390,P<0.01),显著高于HC组[(-2.18±21.45)ng/mL,(t=3.315,P<0.01)];HNC 24 h血Glu(185.8±42.7)μmol/L显著高于HC组[(158.0±43.1)μmol/L,(t=2.916,P<0.01)],72 h Glu(160.6±21.3)μmol/L出现显著降低(t=4.951,P<0.01),亦显著低于HC组[(177.3±43.2)μmol/L,(t=2.190,P<0.05)];28 d病死率[31.7%vs.32.5%,(χ^(2)=0.006,P>0.05)]两组差异无统计学意义;存活者出院时GCS[(7.82±1.86)vs.(8.00±2.60),(t=0.293,P>0.05)]差异亦无统计学意义;HNC组6个月GOS评分预后良好比例明显优于HC组(41.5%vs.20.5%,χ^(2)=4.083,P<0.05),不良反应两组间差异无统计学意义。存活亚组中NSE和Glu表现更加显著;死亡亚组NSE差异无统计学意义,HNC组72 h Glu仍显著降低。结论HNC治疗72 h可以显著降低cTBI患者血NSE浓度,Glu浓度短暂起伏后亦得到显著控制,并能显著改善患者远期预后。冯伟生 刁井地 侯思南 徐继来 张宜波 刘爽 王红 丰广魁 2021实用医学杂志2021,37,17:11
2Pathological significance of tRNA-derived small RNAs in neurological disorders显示文摘Non-coding RNAs(ncRNAs) are a type of RNA that is not translated into proteins. Transfer RNAs(tRNAs), a type of ncRNA, are the second most abundant type of RNA in cells. Recent studies have shown that tRNAs can be cleaved into a heterogeneous population of ncRNAs with lengths of 18–40 nucleotides, known as tRNA-derived small RNAs(tsRNAs). There are two main types of tsRNA, based on their length and the number of cleavage sites that they contain: tRNA-derived fragments and tRNA-derived stress-induced RNAs. These RNA species were first considered to be byproducts of tRNA random cleavage. However, mounting evidence has demonstrated their critical functional roles as regulatory factors in the pathophysiological processes of various diseases, including neurological diseases. However, the underlying mechanisms by which tsRNAs affect specific cellular processes are largely unknown. Therefore, this study comprehensively summarizes the following points:(1) The biogenetics of tsRNA, including their discovery, classification, formation, and the roles of key enzymes.(2) The main biological functions of tsRNA, including its miRNA-like roles in gene expression regulation, protein translation regulation, regulation of various cellular activities, immune mediation, and response to stress.(3) The potential mechanisms of pathophysiological changes in neurological diseases that are regulated by tsRNA, including neurodegeneration and neurotrauma.(4) The identification of the functional diversity of tsRNA may provide valuable information regarding the physiological and pathophysiological mechanisms of neurological disorders, thus providing a new reference for the clinical treatment of neurological diseases. Research into tsRNAs in neurological diseases also has the following challenges: potential function and mechanism studies, how to accurately quantify expression, and the exact relationship between tsRNA and miRNA. These challenges require future research efforts.Chuan Qin Pei-Pei Xu Xin Zhang Chao Zhang Chang-Bin Liu De-Gang Yang Feng Gao Ming-Liang Yang Liang-Jie Du Jian-Jun Li 2020Neural Regeneration Research2020,15,2:5
3白果内酯对大鼠创伤性脑损伤的神经保护作用显示文摘目的探讨白果内酯对大鼠创伤性脑损伤(TBI)的神经保护作用及可能机制。方法自徐州医科大学动物实验中心购买36只200~220 g SD大鼠,雌雄不拘,按数字随机表法分为假手术组、溶剂组以及白果内酯组各12只。假手术组大鼠只开颅,不制备TBI模型,溶剂组以及白果内酯组大鼠应用液压损伤装置制备TBI模型,所有大鼠术后腹腔注射5-溴脱氧尿苷(BrdU)以标准记新生神经元,溶剂组以及白果内酯组大鼠尾静脉分别注射溶剂或白果内酯。术后1、3、7和14 d尾静脉抽血,检测血清丙二醛(MDA)、超氧化物歧化酶(SOD)水平。术后第15 d所有大鼠进行连续5 d的Morris水迷宫试验观察大鼠认知功能情况,然后应用TUNEL法检测损伤区细胞凋亡情况,应用神经元核抗原(NeuN)/BrdU免疫荧光双标检测损伤区皮质新生成熟神经元情况,应用Western blot检测海马组织中双皮质素(DCX)蛋白情况。结果 (1)溶剂组和白果内酯组大鼠血清MDA水平术后1、3 d升高,均高于假手术组(P<0.05);7、14 d回落,溶剂组仍高于假手术组(P<0.05),白果内酯组回落至与假手术组相近水平(P>0.05)。(2)溶剂组和白果内酯组大鼠血清SOD水平术后1、3 d下降,均低于假手术组(P<0.05);7、14 d回升,溶剂组仍低于假手术组(P<0.05),白果内酯组回升至与假手术组相近水平(P>0.05)。(3)大鼠定位巡航实验的逃避潜伏期以溶剂组→白果内酯组→假手术组之序递降(P<0.01),大鼠空间探索试验的平台跨越次数以假手术组→白果内酯组→溶剂组之序递减(P<0.01)。(4)与假手术组比较,溶剂组大鼠空间探索试验的平台跨越次数明显减少,白果内酯组大鼠平台跨越次数也有所减少,但是多于溶剂组(P<0.05)。(5)假手术组大鼠皮质未见到凋亡细胞,溶剂组大鼠损伤区皮质可见较多的凋亡细胞,白果内酯组大鼠损伤区皮质凋亡细胞明显少于溶剂组(P<0.05)。(6)溶剂组大鼠皮质见到少量NeuN^+/BrdU^+双标阳性新生成熟神经元,白果内酯组大鼠损伤区皮质可见到较多NeuN^+/BrdU^+双标阳性新生成熟神经元,明显多于溶剂组(P<0.05)。(7)海马DCX蛋白表达水平以假手术组→白果内酯组→溶剂组之序递降(P<0.05)。结论白果内酯能够降低TBI大鼠体内氧化应激水平,保护神经细胞免于凋亡,而且能促进损伤区皮质以及海马的神经元发生,从而提高TBI大鼠的学习记忆等认知功能。杨泗华 刘希光 李爱民 陈慧珍 2020中国临床研究2020,33,6:2
4Traumatic brain injury induced by exposure to blast overpressure via ear canal显示文摘Exposure to explosive shockwave often leads to blast-induced traumatic brain injury in military and civilian populations.Unprotected ears are most often damaged following exposure to blasts.Although there is an association between tympanic membrane perforation and TBI in blast exposure victims,little is known about how and to what extent blast energy is transmitted to the central nervous system via the external ear canal.The present study investigated whether exposure to blasts directed through the ear canal causes brain injury in LongEvans rats.Animals were exposed to a single blast(0–30 pounds per square inch(psi))through the ear canal,and brain injury was evaluated by histological and behavioral outcomes at multiple time-points.Blast exposure not only caused tympanic membrane perforation but also produced substantial neuropathological changes in the brain,including increased expression of c-Fos,induction of a profound chronic neuroinflammatory response,and apoptosis of neurons.The blast-induced injury was not limited only to the brainstem most proximal to the source of the blast,but also affected the forebrain including the hippocampus,amygdala and the habenula,which are all involved in cognitive functions.Indeed,the animals exhibited long-term neurological deficits,including signs of anxiety in open field tests 2 months following blast exposure,and impaired learning and memory in an 8-arm maze 12 months following blast exposure.These results suggest that the unprotected ear canal provides a locus for blast waves to cause TBI.This study was approved by the Institutional Animal Care and Use Committee at the University of Mississippi Medical Center(Animal protocol#0932 E,approval date:September 30,2016 and 0932 F,approval date:September 27,2019).Yang Ou Brad AClifton Jinghui Li David Sandlin Na Li Li Wu Chunming Zhang Tianwen Chen Jun Huang Yue Yu Jerome Allison Fan Fan Richard JRoman James Shaffery Wu Zhou Yi Pang Hong Zhu 2022Neural Regeneration Research2022,17,1:1
5Homer signaling pathways as effective therapeutic targets for ischemic and traumatic brain injuries and retinal lesions显示文摘Ischemic and traumatic insults to the central nervous system account for most serious acute and fatal brain injuries and are usually characterized by primary and secondary damage.Secondary damage presents the greatest challenge for medical staff;however,there are currently few effective therapeutic targets for secondary damage.Homer proteins are postsynaptic scaffolding proteins that have been implicated in ischemic and traumatic insults to the central nervous system.Homer signaling can exert either positive or negative effects during such insults,depending on the specific subtype of Homer protein.Homer 1b/c couples with other proteins to form postsynaptic densities,which form the basis of synaptic transmission,while Homer 1a expression can be induced by harmful external factors.Homer 1c is used as a unique biomarker to reveal alterations in synaptic connectivity before and during the early stages of apoptosis in retinal ganglion cells,mediated or affected by extracellular or intracellular signaling or cytoskeletal processes.This review summarizes the structural features,related signaling pathways,and diverse roles of Homer proteins in physiological and pathological processes.Upregulating Homer 1a or downregulating Homer 1b/c may play a neuroprotective role in secondary brain injuries.Homer also plays an important role in the formation of photoreceptor synapses.These findings confirm the neuroprotective effects of Homer,and support the future design of therapeutic drug targets or gene therapies for ischemic and traumatic brain injuries and retinal disorders based on Homer proteins.Xiu-Quan Wu Ning Su Zhou Fei Fei Fei 2022Neural Regeneration Research2022,17,7:1
6Acute effects of human protein S administration after traumatic brain injury in mice显示文摘Despite years of effort,no effective acute phase treatment has been discovered for traumatic brain injury.One impediment to successful drug development is entangled secondary injury pathways.Here we show that protein S,a natural multifunctional protein that regulates coagulation,inflammation,and apoptosis,is able to reduce the extent of multiple secondary injuries in traumatic brain injury,and therefore improve prognosis.Mice subjected to controlled cortical impact were treated acutely(10–15 minutes post-injury)with a single dose of either protein S(1 mg/kg)or vehicle phosphate buffered saline via intravenous injection.At 24 hours post-injury,compared to the non-treated group,the protein S treated group showed substantial improvement of edema and fine motor coordination,as well as mitigation of progressive tissue loss.Immunohistochemistry and western blot targeting caspase-3,B-cell lymphoma 2(Bcl-2)along with terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assay revealed that apoptosis was suppressed in treated animals.Immunohistochemistry targeting CD11 b showed limited leukocyte infiltration in the protein S-treated group.Moreover,protein S treatment increased the ipsilesional expression of aquaporin-4,which may be the underlying mechanism of its function in reducing edema.These results indicate that immediate intravenous protein S treatment after controlled cortical impact is beneficial to traumatic brain injury prognosis.Animal Use Protocols(AUPs)were approved by the University Committee on Animal Resources(UCAR)of University of Rochester Medical Center(approval No.UCAR-2008-102 R)on November 12,2013.Xiaowei Wang Jing Tong Xiaodi Han Xiaoming Qi Jun Zhang Erxi Wu Jason H.Huang 2020Neural Regeneration Research2020,15,11:1
7逐步减压术治疗重型颅脑损伤的临床价值及对患者颅内压的改善作用显示文摘目的观察逐步减压术治疗重型颅脑损伤的临床疗效及其对患者颅内压的改善作用。方法回顾性分析太原钢铁(集团)有限公司总医院2015年1月至2020年1月收治的重型颅脑损伤患者120例的临床资料,根据不同治疗方法分组,接受传统去骨瓣减压术治疗的患者64例为对照组,接受逐步减压术治疗的患者56例为逐步减压组,比较两组患者治疗各时间点(术前、术中、术后即刻、术后3个月、术后6个月)颅内压,评估术前及术后6个月患者生活自理能力、昏迷程度、神经功能缺损情况,统计术中及术后6个月内并发症发生情况并进行生活质量评估。结果术前,两组颅内压差异无统计学意义(P>0.05),术中、术后即刻、术后3个月、术后6个月逐步减压组颅内压分别为(30.74±2.51)mmHg、(25.11±2.06)mmHg、(21.34±2.01)mmHg、(16.74±1.54)mmHg,均明显低于对照组的(34.31±3.06)mmHg、(30.64±2.57)mmHg、(26.33±2.35)mmHg、(22.64±1.95)mmHg(t=12.88、19.03、12.40、18.20,均P<0.001)。术前,两组改良巴氏指数评定量表(MBI)、格拉斯哥昏迷评分法(GCS)、美国国立卫生研究院卒中量表(NIHSS)评分差异均无统计学意义(均P>0.05),术后6个月两组MBI及GCS评分均上升,NIHSS均下降,两组术后6个月NIHSS、MBI、GCS评分差异均有统计学意义(t=7.61、6.26、13.07,均P<0.001)。术中及术后6个月,逐步减压组脑梗死、迟发性脑血肿、急性脑膨出发生率均明显低于对照组(χ^(2)=4.23、4.35、4.83,均P<0.05)。生活质量综合问卷(GQOLI-74)多维度评估显示,逐步减压组4个维度(物质、躯体、社会、心理)评分均显著高于对照组,差异均有统计学意义(t=8.16、9.80、8.68、7.76,均P<0.001)。结论该研究首次从患者颅内压、生活质量、术后短中期并发症等多个方面分析逐步减压术用于重型颅脑损伤治疗的可行性,证实重型颅脑损伤患者接受逐步减压术治疗可有效降低患者颅内压,改善其神经功能,预防并发症,同时提高患者生活自理能力及生活质量。郭涛 芦戬 张瑞生 2022中国基层医药2022,29,2:1
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