Hypoxia-ischemia in the immature rodent brain impairs serotonergic neuronal function in certain dorsal raphé nuclei

Neonatal hypoxia-ischemia(HI) results in losses of serotonergic neurons in specific dorsal raphé nuclei. However, not all serotonergic raphé neurons are lost and it is therefore important to assess the function of remaining neurons in order to understand their potential to contribute to neurological disorders in the HI-affected neonate. The main objective of this study was to determine how serotonergic neurons, remaining in the dorsal raphé nuclei after neonatal HI, respond to an external stimulus(restraint stress). On postnatal day 3(P3), male rat pups were randomly allocated to one of the following groups:(i) control + no restraint(n = 5),(ii) control + restraint(n = 6),(iii) P3 HI + no restraint(n = 5) or(iv) P3 HI + restraint(n = 7). In the two HI groups, rat pups underwent surgery to ligate the common carotid artery and were then exposed to 6% O2 for 30 minutes. Six weeks after P3 HI, on P45, rats were subjected to restraint stress for 30 minutes. Using dual immunolabeling for Fos protein, a marker for neuronal activity, and serotonin(5-hydroxytrypamine; 5-HT), numbers of Fos-positive 5-HT neurons were determined in five dorsal raphé nuclei. We found that restraint stress alone increased numbers of Fos-positive 5-HT neurons in all five dorsal raphé nuclei compared to control animals. However, following P3 HI, the number of stress-induced Fos-positive 5-HT neurons was decreased significantly in the dorsal raphé ventrolateral, interfascicular and ventral nuclei compared with control animals exposed to restraint stress. In contrast, numbers of stress-induced Fos-positive 5-HT neurons in the dorsal raphé dorsal and caudal nuclei were not affected by P3 HI. These data indicate that not only are dorsal raphé serotonergic neurons lost after neonatal HI, but also remaining dorsal raphé serotonergic neurons have reduced differential functional viability in response to an external stimulus. Procedures were approved by the University of Queensland Animal Ethics Committee(UQCCR958/08/NHMRC) on February 27, 2009.

Effects of exogenous ganglioside-1 on learning and memory in a neonatal rat model of hypoxia-ischemia brain injury

BACKGROUND： Exogenous ganglioside-1 （GM1） can cross the blood-brain barrier and play a protective role against hypoxia-ischemia-induced brain damage. OBJECTIVE： To examine the possible mechanisms of exogenous GM1 protection in hypoxia-ischemia-induced brain damage in a neonatal rat model by measuring changes in brain mass, pathological morphology, growth-associated protein-43 expression, and neurobehavioral manifestations. DESIGN, TIME AND SETTING： A randomized block-design study was performed at the Immunohistochemistry Laboratory of the Pediatric Research Institute, Children＇s Hospital of Chongqing Medical University from August 2005 to August 2006. MATERIALS： A total of 36 neonatal, 7-day-old, Sprague Dawley rats were used in this experiment. The hypoxia-ischemia-induced brain damage model was established by permanently occluding the right carotid artery, followed by oxygen inhalation at a low concentration （8% O2, 92% N2） for 2 hours, METHODS： All rats were randomly divided into the following groups： GMI, model, and sham operation, with 12 rats each group. Rats in the GM 1 and model groups received hypoxic/ischemic-induced brain damage. Rats in the GM1 group received injections of GM1 （i.p., 20 mg/kg） at 0, 24, 48, 72, 96, 120, and 144 hours following models established, and rats in the model group were administered （i.p.） the same amount of saline. The right carotid artery was separated, but not ligated, in the sham operation group rats. MAIN OUTCOME MEASURES： At 1 week after surgery, expression of growth-associated protein-43, a marker of neural development and plasticity, was detected in the hippocampal CA3 region by immunohistochemistry. Brain mass was measured, and the pathological morphology was observed. At 4 weeks after surgery, behavioral changes in the remaining rats were tested by Morris water maze, and growth-associated protein-43 expression was measured. RESULTS： （1） In the GMI and sham operation groups, growth-associated protein-43 expression was greater in the hippocampal CA3 region compared to the model group 1 week after surgery （P 〈 0.05）. In all three groups, brain weight of the right hemisphere was significantly less than the left hemisphere, in particular in the model group （P 〈 0.05）. In the GMI group, the weight difference between two hemispheres, as well as the extent of damage in the right hemisphere, was less than the model group （P 〈 0.01 ）. In the sham operation Uoup, brain tissue consisted of integrated structures and ordered cells. In the model group, the cerebral cortex layers of the right hemisphere were not defined, neurons were damaged, and neurons were disarranged in the hippocampal area. In the GM1 group, neurons were dense in the right cerebral cortex and hippocampal area, with no significant change in glial proliferation. （2） The average time of escape latency in the GM1 group was shortened 4 weeks alter surgery, and significantly less than the model group （P 〈 0.05）. In addition, the frequency platform passing in the GMI group was significantly greater than the model group （P 〈 0.01）. CONCLUSION： Exogenous GM1 may reduce brain injury and improve learning and memory in hypoxia-ischemia-induced brain damage rats. This protection may be associated with increased growth-associated protein-43 expression, which is involved in neuronal remodeling processes.

Transfer of mitochondria from mesenchymal stem cells derived from induced pluripotent stem cells attenuates hypoxia-ischemia-induced mitochondrial dysfunction in PC12 cells

Mitochondrial dysfunction in neurons has been implicated in hypoxia-ischemia-induced brain injury.Although mesenchymal stem cell therapy has emerged as a novel treatment for this pathology,the mechanisms are not fully understood.To address this issue,we first co-cultured 1.5×10^5 PC12 cells with mesenchymal stem cells that were derived from induced pluripotent stem cells at a ratio of 1:1,and then intervened with cobalt chloride(CoCl2)for 24 hours.Reactive oxygen species in PC12 cells was measured by Mito-sox.Mitochondrial membrane potential(ΔΨm)in PC12 cells was determined by JC-1 staining.Apoptosis of PC12 cells was detected by terminal deoxynucleotidal transferase-mediated dUTP nick end-labeling staining.Mitochondrial morphology in PC12 cells was examined by transmission electron microscopy.Transfer of mitochondria from the mesenchymal stem cells derived from induced pluripotent stem cells to damaged PC12 cells was measured by flow cytometry.Mesenchymal stem cells were induced from pluripotent stem cells by lentivirus infection containing green fluorescent protein in mitochondria.Then they were co-cultured with PC12 cells in Transwell chambers and treated with CoCl2 for 24 hours to detect adenosine triphosphate level in PC12 cells.CoCl2-induced PC12 cell damage was dose-dependent.Co-culture with mesenchymal stem cells significantly reduced apoptosis and restoredΔΨm in the injured PC12 cells under CoCl2 challenge.Co-culture with mesenchymal stem cells ameliorated mitochondrial swelling,the disappearance of cristae,and chromatin margination in the injured PC12 cells.After direct co-culture,mitochondrial transfer from the mesenchymal stem cells stem cells to PC12 cells was detected via formed tunneling nanotubes between these two types of cells.The transfer efficiency was greatly enhanced in the presence of CoCl2.More importantly,inhibition of tunneling nanotubes partially abrogated the beneficial effects of mesenchymal stem cells on CoCl2-induced PC12 cell injury.Mesenchymal stem cells reduced CoCl2-induced PC12 cell injury and these effects were in part due to efficacious mitochondrial transfer.

Brain Pathology in COVID-19:Clinical Manifestations and Potential Mechanisms

Neurological manifestations of coronavirus disease 2019(COVID-19)are less noticeable than the respiratory symptoms,but they may be associated with disability and mortality in COVID-19.Even though Omicron caused less severe disease than Delta,the incidence of neurological manifestations is similar.More than 30%of patients experienced“brain fog”,delirium,stroke,and cognitive impairment,and over half of these patients presented abnormal neuroimaging outcomes.In this review,we summarize current advances in the clinical findings of neurological manifestations in COVID-19 patients and compare them with those in patients with influenza infection.We also illustrate the structure and cellular invasion mechanisms of SARS-CoV-2 and describe the pathway for central SARS-CoV-2 invasion.In addition,we discuss direct damage and other pathological conditions caused by SARS-CoV-2,such as an aberrant interferon response,cytokine storm,lymphopenia,and hypercoagulation,to provide treatment ideas.This review may offer new insights into preventing or treating brain damage in COVID-19.

Pathological verification of corticospinal tract Wallerian degeneration in a rat model of brain ischemia

Although neuroimaging is commonly utilized to study Wallerian degeneration, it cannot display Wallerian degeneration early after brain injury. In the present study, we attempted to examine pathologically the process of Wallerian degeneration early after brain injury. Cerebral peduncle demyelination was observed at 3 weeks post brain ischemia, followed by demyelination in the cervical enlargement at 6 weeks. Anterograde tracing of the corticospinal tract with biotinylated dextran amine showed that following serious neurologic deficit, the tracing of the corticospinal tract of the intemal capsule, cerebral peduncle, and cervical enlargement indicated serious Wallerian degeneration.

Pathological Characteristics of Liver Allografts from Donation after Brain Death Followed by Cardiac Death in Pigs

Donation after brain death followed by circulatory death （DBCD） is a unique practice in China. The aim of this study was to define the pathologic characteristics of DBCD liver allografts in a porcine model. Fifteen male pigs （25-30 kg） were allocated randomly into donation after brain death （DBD）, donation after circulatory death （DCD） and DBCD groups. Brain death was induced by aug- menting intracranial pressure. Circulatory death was induced by withdrawal of life support in DBCD group and by venous injection of 40 mL 10% potassium chloride in DCD group. The donor livers were perfused in situ and kept in cold storage for 4 h. Liver tissue and common bile duct samples were col- lected for hematoxylin and eosin staining, TUNEL testing and electron microscopic examination. Spot necrosis was found in hepatic parenchyma of DBD and DBCD groups, while a large area of necrosis was shown in DCD group. The apoptosis rate of hepatocytes in DBD [（0.56±0.30）%] and DBCD [（0.50 ±0.11）%] groups was much lower than that in DCD group [（3.78±0.33）%] （P〈0.05）. And there was no significant difference between DBD group and DBCD group （P〉0.05））. The structures of bile duct were intact in both DBD and DBCD groups, while the biliary epithelium was totally damaged in DCD group. Under electron microscope, the DBD hepatocytes were characterized by intact cell membrane, well-organized endoplasmic reticulum, mild mitochondria edema and abundant glycogens. Broken cell membrane, mild inflammatory cell infiltration and sinusoidal epithelium edema, as well as reduced glycogen volume, were found in the DBCD hepatocytes. The DCD hepatocytes had more profound cell organelle injury and much less glycogen storage. In conclusion, the preservation injury of DBCD liver allografts is much less severe than that of un-controlled DCD, but more severe than that of DBD liver allografts under electron microscope, which might reflect post-transplant liver function to some extent.

Pathological changes in the lung and brain of mice during heat stress and cooling treatment

BACKGROUND： Heatstroke often leads to multiple organ dysfunction syndrome （MODS） with a death rate of 40% or a neurological morbidity of 30%. These high rates in patients with heatstroke are largely due to the progression of heat stress to MODS, resulting in no specifi c treatment available. This study aimed to develop a mouse model of heat stress and determine the pathological changes in the lung and brain during heat stress and cooling treatment.METHODS： A mouse model of heat stress was established in a pre-warmed incubator set at 35.5 ± 0.5°C and with a relative humidity of 60% ± 5%. Rectal temperature was monitored, and at a temperature of 39 °C, 40 °C, 41 °C, or 42 °C, the mice were sacrifi ced. The remaining animals were removed from the incubator and cooled at an ambient temperature of 25 ± 0.5 °C and a humidity of 35% ± 5% for 12 or 24 hours at a temperature of 41 °C or for 6 hours at a temperature of 42 °C. The control mice were sham-heated at a temperature of 25 ± 0.5 °C and a humidity of 35% ± 5%. The lungs and brains of all animals were isolated. Hematoxylin and eosin staining and light microscopy were performed to detect pathological changes.RESULTS： All mice demonstrated a uniform response to heat stress. A low degree of heat stress induced marked pathological changes of the lungs. With the rise of the temperature to 42°C, progressively greater damage to the lungs with further congestion of the lung matrix, asystematic hemorrhage of alveolar space, abscission of alveolar epithelial cells, and disappearance of pulmonary alveolus tissue structure were detected. However, absorption of congestion and hemorrhage as well as recovery of pulmonary alveolus tissue structure was observed following cooling treatment at an ambient temperature. With a low degree of heat stress, the brain only showed moderate edema. Neuronal denaturation and necrosis were detected at a temperature of 42°C. Interestingly, the lesions in the brain were further aggravated at 42 °C regardless of cooling treatment, but recovery was observed after cooling treatment at 41 °C.CONCLUSIONS： The pathological changes of the lungs and brain of mice showed distinctive lesions following heat stress and cooling treatment, and they were correlated with the time and duration of cooling treatment. The results of this study are helpful for further study of the mechanisms linking heatstroke.

Emerging roles of astrocytes in blood-brain barrier disruption upon amyloid-beta insults in Alzheimer's disease

Blood-brain barrier disruption occurs in the early stages of Alzheimer’s disease.Recent studies indicate a link between blood-brain barrier dysfunction and cognitive decline and might accelerate Alzheimer’s disease progression.Astrocytes are the most abundant glial cells in the central nervous system with important roles in the structural and functional maintenance of the blood-brain barrier.For example,astrocytic cove rage around endothelial cells with perivascular endfeet and secretion of homeostatic soluble factors are two major underlying mechanisms of astrocytic physiological functions.Astrocyte activation is often observed in Alzheimer’s disease patients,with astrocytes expressing a high level of glial fibrillary acid protein detected around amyloid-beta plaque with the elevated phagocytic ability for amyloid-beta.Structural alte rations in Alzheimer’s disease astrocytes including swollen endfeet,somata shrinkage and possess loss contribute to disruption in vascular integrity at capillary and arte rioles levels.In addition,Alzheimer’s disease astrocytes are skewed into proinflammatory and oxidative profiles with increased secretions of vasoactive mediators inducing endothelial junction disruption and immune cell infiltration.In this review,we summarize the findings of existing literature on the relevance of astrocyte alte ration in response to amyloid pathology in the context of blood-brain barrier dysfunction.First,we briefly describe the physiological roles of astrocytes in blood-brain barrier maintenance.Then,we review the clinical evidence of astrocyte pathology in Alzheimer’s disease patients and the preclinical evidence in animal and cellular models.We further discuss the structural changes of blood-brain barrier that correlates with Alzheimer’s disease astrocyte.Finally,we evaluate the roles of soluble factors secreted by Alzheimer’s disease astrocytes,providing potential molecular mechanisms underlying blood-brain barrier modulation.We conclude with a perspective on investigating the therapeutic potential of targeting astrocytes for blood-brain barrier protection in Alzheimer’s disease.

Morphologic damage of neurons in hippocampus (CA-1) following focal brain cortex contusion:a quantitative histopathologic study

The present study was designed to investigate the hippocampus injury in response to focal brain trauma. Neuron damage in the cortex and the hippocampus (CA-1) was assessed quantitatively with light microscope through a cerebral contusion model of rat. The

肺癌脑转移瘤的MRI影像特征与病理组织学的相关性分析

目的探讨肺癌脑转移瘤患者的MRI影像学特征以及与病理组织学的相关性。方法选取肺癌脑转移瘤患者34例为研究对象,对患者MRI检查和病理组织学结果进行整理。结果本组34例患者中,23例腺癌,2例鳞癌,9例小细胞肺癌;腺癌多发数目高于鳞癌、小细胞肺癌(P<0.05);腺癌肿瘤大小高于鳞癌、小细胞肺癌(P<0.05);鳞癌脑转移瘤水肿程度最高,其次为小细胞肺癌,三组对比有差异(P<0.05);小细胞肺癌强化不规则状特点最突出,其次为腺癌,三组对比有差异(P<0.05)。结论肺癌脑转移瘤MRI影像学特征与病理组织学之间有密切关联性,故可将MRI可作为识别诊断肺癌脑转移瘤的重要手段。

Brain-derived neurotrophic factor and its related enzymes and receptors play important roles after hypoxic-ischemic brain damage

Brain-derived neurotrophic factor(BDNF) regulates many neurological functions and plays a vital role during the recovery from central nervous system injuries. However, the changes in BDNF expression and associated factors following hypoxia-ischemia induced neonatal brain damage, and the significance of these changes are not fully understood. In the present study, a rat model of hypoxic-ischemic brain damage was established through the occlusion of the right common carotid artery, followed by 2 hours in a hypoxic-ischemic environment. Rats with hypoxic-ischemic brain damage presented deficits in both sensory and motor functions, and obvious pathological changes could be detected in brain tissues. The m RNA expression levels of BDNF and its processing enzymes and receptors(Furin, matrix metallopeptidase 9, tissuetype plasminogen activator, tyrosine Kinase receptor B, plasminogen activator inhibitor-1, and Sortilin) were upregulated in the ipsilateral hippocampus and cerebral cortex 6 hours after injury;however, the expression levels of these m RNAs were found to be downregulated in the contralateral hippocampus and cerebral cortex. These findings suggest that BDNF and its processing enzymes and receptors may play important roles in the pathogenesis and recovery from neonatal hypoxic-ischemic brain damage. This study was approved by the Animal Ethics Committee of the University of South Australia(approval No. U12-18) on July 30, 2018.

苓桂气化2号方对射血分数保留心力衰竭大鼠心脏结构和舒张功能的影响

目的观察苓桂气化2号方对射血分数保留心力衰竭(heart failure with preserved ejection fraction,HFpEF)大鼠心脏结构和舒张功能的影响。方法10只7周龄的威斯塔京都大鼠作为正常组,40只自发性高血压大鼠建立复合糖尿病、高血压、高血脂的HFpEF大鼠模型,造模期间死亡3只。造模成功后,所有造模成功的大鼠随机分为模型组(9只)、恩格列净组(10只)、低剂量组(9只)和高剂量组(9只)。正常组和模型组给予等量生理盐水,恩格列净组给予恩格列净1.8 mg/(kg·d),低、高剂量组分别给予苓桂气化2号方浸膏8.1 g/(kg·d)和16.2 g/(kg·d),持续4周。给药结束后,使用超声心动图测量每组大鼠的左室舒末内径(left ventricular end diastolic diameter,LVEDD)、左房内径(left atrial diameter,LAD)、右房内径(right atrial diameter,RAD)、室间隔厚度(interventricular septal thickness,IVST)、左室射血分数(left ventricular ejection fraction,LVEF)、等容舒张时间(isovolumic relaxation time,IVRT)、舒张早期二尖瓣血流速度(left ventricular early diastolic filling peak velocity,E)与二尖瓣环心肌运动速度(early diastolic lateral mitral annulus velocity,e′)的值。使用酶联免疫吸附法检测心钠素(atrial natriuretic peptide,ANP)和脑钠肽(B-type brain natriuretic peptide,BNP)水平。苏木精—伊红染色观察左房心肌组织病理变化,马松染色染色观察心肌组织纤维化。结果与正常组比较,模型组大鼠出现呼吸急促、食欲下降、易怒等情况,心脏超声检测显示LVEDD、LAD、RAD显著增大(P<0.01),IVST、E/e′、IVRT显著增加(P<0.01);血清ANP、BNP水平显著升高(P<0.01)。与模型组相比,各给药组大鼠精神佳、反应灵敏、纳食饮水相对较多,心脏超声相关参数显示LVEDD、LAD、RAD、IVST以及E/e′、IVRT均有明显改善(P<0.05);血清ANP、BNP水平均明显降低(P<0.05)。结论苓桂气化2号方可能通过减轻心肌肥厚及纤维化改善HFpEF大鼠的心脏重构和舒张功能障碍,是治疗HFpEF的潜在有效方剂。

脑源性神经营养因子在轻型子宫内膜异位症中的表达及意义

目的:探讨脑源性神经营养因子(BDNF)在轻型子宫内膜异位症中的表达,评估BDNF作为轻度子宫内膜异位症临床标志物的适用性及诊断价值。方法:选取2020~2022年中山市博爱医院收治的因子宫内膜异位症及输卵管性不孕就诊的行腹腔镜手术的患者159例为研究对象,分为研究组(腹腔镜及病理证实的子宫内膜异位症患者,分为轻型子宫内膜异位症与重型子宫内膜异位症)111例与对照组(输卵管性不孕患者)48例。术前收集所有患者的外周血,通过酶联免疫吸附试验(ELISA)方法定量检测BDNF及CA125水平。比较研究组与对照组血清BDNF及CA125水平;比较轻型子宫内膜异位症患者与对照组血清BDNF及CA125水平,分析BDNF对轻型子宫内膜异位症的预测价值。结果:研究组血清BDNF及CA125水平均高于对照组,差异有统计学意义(P<0.05);轻型子宫内膜异位症患者血清BDNF及CA125水平均高于对照组,差异有统计学意义(P<0.05);与CA125水平比较,BDNF具有更大的曲线下面积(AUC),BDNF作为诊断轻型子宫内膜异位症的敏感度和特异性分别为76.2%、62.2%;重型子宫内膜异位症患者血清BDNF及CA125水平高于轻型子宫内膜异位症患者,其中BDNF水平在两组中比较差异无统计学意义(P>0.05);CA125在重度子宫内膜异位症患者中显著升高,差异有统计学意义(P<0.05)。结论:轻型子宫内膜异位症中血清BDNF升高,可作为预测轻型子宫内膜异位症的指标。

中线部位和脑室节细胞胶质瘤临床病理分析及文献复习

目的探讨中线部位和脑室节细胞胶质瘤的临床病理及分子遗传学特点。方法收集11例中线部位和脑室节细胞胶质瘤患者的临床特征、免疫表型及分子检测结果,并复习总结相关文献。结果镜下观察节细胞胶质瘤由异常神经元和肿瘤性增生的胶质细胞构成,免疫表型NeuN、MAP2可标记肿瘤中的神经元成分,GFAP和Olig-2标记出了肿瘤性神经胶质细胞成分;分子遗传学常存在BRAFV600E点突变,但也可发现存在其他形式BRAF基因以及MAPK信号通路基因的改变。随访病例多数预后良好。结论发生在中线部位及脑室的节细胞胶质瘤较为罕见,对于发生于不典型部位的这种低级别神经上皮肿瘤,要将其纳入鉴别诊断中,可在形态学基础上,结合免疫组织化学以及分子检测结果进行综合分析。

TBI后应激性肠屏障损害的研究进展

创伤性脑损伤后应激性肠屏障损害增加了患者的死亡风险,严重影响疾病预后,目前其发病机制和治疗策略仍不完全清楚。本文旨在总结创伤性脑损伤应激性肠屏障损害的病理机制和保护策略等关键问题的研究进展,发现肠上皮细胞通透性增加、紧密连接、内质网应激、细胞自噬、缺血再灌注损伤可能是创伤性脑损伤应激后肠屏障损害的主要机制。此外,本文还综述了迷走神经刺激、益生菌、外源性补充饥饿素、氧疗等对创伤性脑损伤后应激性肠屏障损害的保护作用。本文将为探索精准有效的创伤性脑损伤后应激性肠屏障损害防治提供新视角和干预靶点。

DCE-MRI血流动力学参数在高、低级别胶质瘤鉴别中的应用及其与分子生物学标记物水平的相关性

目的:探讨动态增强磁共振成像(DCE-MRI)血流动力学参数在高、低级别胶质瘤鉴别中的应用,分析其与分子生物学标记物水平的相关性。方法:选取86例脑胶质瘤患者为研究对象。以病理结果作为金标准,按WHO肿瘤分类标准,将其分为低级别组(n=41)、高级别组(n=45),获得常规和动态增强MRI扫描参数数值,通过受试者工作特征曲线(ROC)分析DCE-MRI血流动力学参数对高、低级别胶质瘤的鉴别价值,Pearson分析各血流动力学参数与癌组织分子生物学标志物的相关性。结果:高级别组DCE-MRI血流动力学参数Ktrans、Kep、Ve水平均高于低级别组(P<0.05);高级别组与低级别组Vp水平比较,差异无统计学意义(P>0.05);DCE-MRI血流动力学参数Ktrans、Kep、Ve联合检测鉴别高、低级别脑胶质瘤ROC曲线下面积(AUC)为0.927,高于单独检测AUC(0.822、0.803、0.785),敏感度为91.11%、特异度为80.49%(P<0.05);高级别组脑胶质瘤分子生物学标记物VEGF mRNA、Ki-67 mRNA表达水平高于低级别组(P<0.05);Pearson相关性分析显示,脑胶质瘤DCE-MRI血流动力学参数Ktrans、Kep、Ve水平与癌组织VEGF mRNA、Ki-67 mRNA表达水平正相关(r=0.522、0.415、0.323、0.483、0.376、0.274,P<0.05)。结论:高级别脑胶质瘤DCE-MRI血流动力学参数Ktrans、Kep、Ve水平均高于低级别胶质瘤,且与癌组织分子生物学标记物VEGF、Ki-67表达水平正相关,可用于临床高、低级别脑胶质瘤鉴别。

血清胶质纤维酸性蛋白、甲基化CpG结合蛋白2对脑胶质瘤的诊断价值及其与病理特征的相关性分析

目的探讨血清胶质纤维酸性蛋白(GFAP)、甲基化CpG结合蛋白2(MeCP2)对脑胶质瘤的诊断价值及其与病理特征的相关性。方法回顾性选取2021年1月至2024年1月南京医科大学附属脑科医院(南京脑科医院)收治的80例脑胶质瘤患者,将其作为胶质瘤组,选取本院同期收治的80例非胶质瘤颅内良性肿瘤患者作为对照组。应用双抗体夹心法检测两组患者血清GFAP表达水平,应用荧光定量聚合酶链反应法检测肿瘤组织MeCP2表达水平。比较脑胶质瘤患者与对照组的GFAP、MeCP2表达水平,并建立ROC曲线分析GFAP、MeCP2对脑胶质瘤的诊断价值。分析不同病理特征脑胶质瘤患者GFAP、MeCP2表达水平,并采用Spearman相关性分析GFAP、MeCP2与脑胶质瘤病理特征的相关性。结果胶质瘤组患者GFAP、MeCP2表达水平分别为(81.74±7.47)ng/L、2.31±0.31,均高于对照组[(5.35±1.32)ng/L、0.72±0.16],差异均有统计学意义(P<0.05)。绘制ROC曲线结果显示,GFAP、MeCP2、两者联合诊断脑胶质瘤的曲线下面积(AUC)分别为0.721、0.698、0.897。GFAP、MeCP2两者联合对脑胶质瘤的诊断AUC高于两者单一诊断。病理分级Ⅳ级、远处转移患者GFAP水平均高于其他分级、未远处转移,差异均有统计学意义(P<0.05)。病理分级Ⅳ级、肿瘤大小≥3 cm、远处转移患者MeCP2水平均高于其他分级、肿瘤大小<3 cm、未远处转移患者,差异均有统计学意义(P<0.05)。Spearman相关分析结果表明,GFAP与脑胶质瘤不同病理分级、远处转移均呈正相关(r=0.579、0.378,P<0.05);MeCP2与脑胶质瘤不同病理分级、远处转移、脑胶质瘤肿瘤大小均呈正相关(r=0.657、0.457、0.384,P<0.05)。结论胶质纤维酸性蛋白、甲基化CpG结合蛋白2对于脑胶质瘤均具有重要诊断参考价值,两者联合诊断敏感度、特异度更高,且两者与脑胶质瘤的病理分级、肿瘤大小、远处转移情况密切相关。

Using the endocannabinoid system as a neuroprotective strategy in perinatal hypoxic-ischemic brain injury

One of the most important causes of brain injury in the neonatal period is a perinatal hypoxicischemic event.This devastating condition can lead to long-term neurological deficits or even death.After hypoxic-ischemic brain injury,a variety of specific cellular mechanisms are set in motion,triggering cell damage and finally producing cell death.Effective therapeutic treatments against this phenomenon are still unavailable because of complex molecular mechanisms underlying hypoxic-ischemic brain injury.After a thorough understanding of the mechanism underlying neural plasticity following hypoxic-ischemic brain injury,various neuroprotective therapies have been developed for alleviating brain injury and improving long-term outcomes.Among them,the endocannabinoid system emerges as a natural system of neuroprotection.The endocannabinoid system modulates a wide range of physiological processes in mammals and has demonstrated neuroprotective effects in different paradigms of acute brain injury,acting as a natural neuroprotectant.The aim of this review is to study the use of different therapies to induce long-term therapeutic effects after hypoxic-ischemic brain injury,and analyze the important role of the endocannabinoid system as a new neuroprotective strategy against perinatal hypoxic-ischemic brain injury.

Developmental changes of glutamate acid decarboxylase 67 in mouse brain after hypoxia ischemia

Objective To study the developmental changes of glutamic acid decarboxylase-67 （ GAD-67, a GABA synthetic enzyme） in normal and hypoxic ischemic （HI） brain. Methods C57/BL6 mice on postnatal day （P） 5, 9, 21 and 60, corresponding developmentally to premature, term, juvenile and adult human brain were investigated by using both Western blot and immunohistochemistry methods either in normal condition or after hypoxic ischemic insult. Results The immunoreactivity of GAD67 was up regulated with brain development and significant difference was seen between mature （P21, P60） and immature （P5, P9） brain. GAD67 immunoreactivity decreased in the ipsilateral hemisphere in all the ages after hypoxia ischemia （HI） insult, but, significant decrease was only seen in the immature brain. Double labeling of GAD67 and cell death marker, TUNEL, in the cortex at 8h post-HI in the P9 mice showed that （15.6±7.0）% TUNEL positive cells were GAD67 positive which was higher than that of P60 mice. Conclusion These data suggest that GABAergic neurons in immature brain were more vulnerable to HI insult than that of mature brain.

脑干胶质瘤病理学分级预测因素及与APT成像的关系研究

目的:探讨脑干胶质瘤病理学分级的预测因素及与酰胺质子转移(amide proton transfer,APT)成像的关系,旨在为高级别胶质瘤患者早期诊断识别及后续预测模型构建提供借鉴。方法:回顾并纳入2019年1月—2023年1月于第九〇九医院行手术治疗并接受APT成像检查的脑干胶质瘤患者79例,根据病理学分级标准分为高级别组(38例)和低级别组(41例);采用单因素分析和多因素logistic回归分析评价脑干胶质瘤病理学分级的独立预测因素,并分析脑干胶质瘤病理学分级预测因素的预测效能。结果:单因素分析结果显示,囊性病变、病灶最大径、APT成像信号强度平均值及最大值均可能与脑干胶质瘤病理学分级相关(P<0.05);多因素logistic分析结果显示,囊性病变、病灶最大径≥2 cm、APT成像信号强度平均值及最大值均是脑干胶质瘤病理学分级的独立预测因素(P<0.05)。利用囊性病变、病灶最大径≥2 cm、APT成像信号强度平均值、APT成像信号强度最大值及logistic模型预测概率对脑干胶质瘤病理学分级情况进行预测,最佳截断值分别为0.50、0.50、2.95%、4.11%、37.85%,约登指数分别为38.19%、44.42%、51.73%、42.17%、65.28%。结论:囊性病变、病灶最大径与APT成像信号强度可作为脑干胶质瘤病理学分级的独立预测因素,且APT成像信号强度平均值具有更佳的预测效能。