Hyperbaric oxygenation prevents delayed neuronal death following transient ischaemia in the gerbil hippocampus

The mechanism of the neuroprotective effect of hyperbaric oxygenation remains unclear although its clinical benefits have been well recognized for human ischaemic neuronal disease. The preventive effect of hyperbaric oxygenation against delayed neuronal death was investigated in the gerbil following transient forebrain ischaemia. Delayed neuronal death in the gerbil was produced by clips on both the common carotid arteries (10 min). Morphological examination was carried out after several protocols of hyperbaric oxygenation, modified from the protocols for human ischaemic neuronal disease. Neurons in the hippocampal CA₁ were well preserved in the gerbils treated with hyperbaric oxygenation, more so than in the gerbils with no hyperbaric oxygenation. Moreover, more neurons were preserved in the CA₁ treated with hyperbaric oxygenation within 6 h of the ischaemia, than when the hyperbaric oxygenation was started 24 h after the ischaemia. The induction of heat shock proteins (HSP72 and HSP27) became weaker in the gerbils with hyperbaric oxygenation than in those without hyperbaric oxygenation, as seen immunohistochemically. We also observed an increase in dense bodies, that were shown to be lysosomes and myelinoid structures in the cytoplasm of the neurons ultrastructurally, in the hippocampus with hyperbaric oxygenation. However, no oxygen toxicity to the neurons was detected, up to at least two atmospheres absolute. This experimental system was useful to investigate the preventive mechanism of hyperbaric oxygenation against delayed neuronal death in the gerbil, and to determine the clinical indications and the most effective protocol for hyperbaric oxygenation for ischaemic neuronal damage in the human brain.     

Regional distribution of heme oxygenase, HSP70, and glutathione in brain: relevance for endogenous oxidant/antioxidant balance and stress tolerance

It is generally recognized that lipid peroxides play an important role in the pathogenesis of several diseases and that sulfhydryl groups are critically involved in cellular defense against endogenous or exogenous oxidants. Recent evidence indicates that lipid peroxides directly participate in induction of cytoprotective proteins, such as heat shock proteins (Hsps), which play a central role in the cellular mechanisms of stress tolerance. Heme oxygenase (HO) is a stress protein that has been implicated in defense mechanisms against agents that may induce oxidative injury, such as endotoxins, cytokines and heme and its induction represents a common feature in a number of neurodegenerative diseases. In the present report we studied regional distribution of heme oxygenase (HO) activity and protein expression, together with that of Hps70, in brain of C57BL6 mice. Endogenous lipid peroxidation was investigated on the basis of the analysis of ultra weak chemiluminescence, hydro peroxides and lipid soluble fluorescent products, and compared to the regional distribution of thiols, antioxidant enzymes and trace metals. Our results show that levels of HO activity and expression of inducible Hsp70 and the ratio of GSH/GSSG in the different brain regions examined were positively correlated with the content of peroxides. Substantia Nigra was the brain area exhibiting the highest levels of HO-2, constitutive and inducible Hsp70, GSSG, peroxides, iron, and calcium, in contrast with the lowest content in GSH, GSH/GSSG ratio and glutathione reductase activity, compared to the other cerebral regions examined. Among these, cortex showed the lowest levels of HO-2, Hsp70, GSSG and peroxides that were associated with the highest levels of GSH and GSH/GSSG ratio. These data support the hypothesis that the glutathione redox state and basal peroxides can directly participate in the signaling pathways of heat shock protein expression and hence of stress tolerance.     

深部电刺激伏隔核对吗啡成瘾大鼠复吸后伏隔核内γ-氨基丁酸含量变化的影响

目的研究深部电刺激(deep brain stimulation,DBS)双侧伏隔核对吗啡成瘾大鼠复吸后伏隔核内γ-氨基丁酸(γ-aminobutyric Acid,GABA)含量的影响。方法手术前使用条件性位置偏爱试验(conditionedplace preference,CPP)筛选无自然偏爱大鼠,随机分组后DBS组行电极植入术,术后10天采用固定剂量吗啡皮下注射(10mg.Kg-1)建立吗啡成瘾大鼠模型(使用CPP证实)。通过改进的DBS电路进行电刺激(频率130Hz,电流300uA,电压1V,1h.d-1),在不同的时间点使用CPP证实DBS组大鼠戒断成功后再皮下给予小剂量吗啡(3mg.Kg-1),24h后使用CPP验证吗啡成瘾大鼠复吸模型建立成功。CPP试验结束后于冰台上按大鼠脑立体定位图谱取伏隔核行高效液相色谱法(high performance liquid chromatography,HPLC)测定GABA含量。结果①皮下注射固定剂量吗啡能够使大鼠成瘾,DBS能够有效抑制吗啡复吸行为;②morphine+DBS组大鼠伏隔核内GABA含量与吗啡组,morphine+sham组差异明显。结论 DBS双侧伏隔核使吗啡成瘾大鼠复吸后伏隔核内GABA含量增加。     

Rab3 Proteins and SNAP-25, Essential Components of the Exocytosis Machinery in Conventional Synapses, are Absent from Ribbon Synapses of the Mouse Retina

GTP-binding rab proteins, present in synaptic vesicles and endocrine secretory granules, have been shown to be involved in the control of regulated exocytosis. We found rab3 proteins in immunoblots of diverse areas of the mouse central nervous system (spinal cord, olfactory bulb, hippocampus, cerebellum and neocortex). Immunohistochemical observations at light- and electron-microscopical levels in the hippocampus and other areas revealed rab3 proteins in virtually all synaptic fields and terminals of the areas investigated. In the retina, rab3A immunoreactivity was confined to the inner and outer plexiform layers. Ultrastructural examination revealed that rab3A was present in conventional terminals in the inner plexiform layer and in horizontal cell processes of the outer plexiform layer. In contrast ribbon synapses, which play a key role in transferring information from the photoreceptor cells to the central nervous system, were immunonegative. We also tested whether other proteins of the rab3 family are present in ribbon synapses. However, using an antibody recognizing rab3B and rab3C in addition to rab3A, we found no immunoreactivity in these synapses. Interestingly, we observed also no immunoreactivity for synaptosomal-associated protein 25 (SNAP-25) in ribbon synapses, but conventional synapses and horizontal cell processes were heavily stained. Our data show that the known rab3 and SNAP-25 isoforms, which are components of the secretory apparatus of conventional synapses, are absent from ribbon synapses of the retina. Our observations suggest different mechanisms of transmitter exocytosis in conventional and ribbon terminals.     

Parallel group ICA+ICA: Joint estimation of linked functional network variability and structural covariation with application to schizophrenia

There is growing evidence that rather than using a single brain imaging modality to study its association with physiological or symptomatic features, the field is paying more attention to fusion of multimodal information. However, most current multimodal fusion approaches that incorporate functional magnetic resonance imaging (fMRI) are restricted to second‐level 3D features, rather than the original 4D fMRI data. This trade‐off is that the valuable temporal information is not utilized during the fusion step. Here we are motivated to propose a novel approach called “parallel group ICA+ICA” that incorporates temporal fMRI information from group independent component analysis (GICA) into a parallel independent component analysis (ICA) framework, aiming to enable direct fusion of first‐level fMRI features with other modalities (e.g., structural MRI), which thus can detect linked functional network variability and structural covariations. Simulation results show that the proposed method yields accurate intermodality linkage detection regardless of whether it is strong or weak. When applied to real data, we identified one pair of significantly associated fMRI‐sMRI components that show group difference between schizophrenia and controls in both modalities, and this linkage can be replicated in an independent cohort. Finally, multiple cognitive domain scores can be predicted by the features identified in the linked component pair by our proposed method. We also show these multimodal brain features can predict multiple cognitive scores in an independent cohort. Overall, results demonstrate the ability of parallel GICA+ICA to estimate joint information from 4D and 3D data without discarding much of the available information up front, and the potential for using this approach to identify imaging biomarkers to study brain disorders.     

Distribution of muscarinic cholinergic high and low affinity agonist binding sites: A light microscopic autoradiographic study

The distribution of high vs. low affinity muscarinic agonist binding sites has been determined using quantitative techniques of receptor autoradiography. The low affinity agonist sites predominate in many regions of the forebrain including the cerebral cortex, striatum, hippocampus, amygdala and thalamus. The high affinity agonist sites predominate in the brainstem and represent exclusively the type of muscarinic cholinergic receptor normally present in the principal nucleus of the trigeminal nerve, facial nerve nucleus, hypoglossal nerve nucleus, and in the ventral horn of the spinal cord. The regional localization of these subpopulations provides valuable information for future studies which seek to determine the functional importance of subtypes of muscarinic agonist binding sites.     

Intraoperative subdural low-noise EEG recording of the high frequency oscillation in the somatosensory evoked potential

Objective

The detectability of high frequency oscillations (HFO, >200 Hz) in the intraoperative ECoG is restricted by their low signal-to-noise ratio (SNR). Using the somatosensory evoked HFO, we quantify how HFO detectability can benefit from a custom-made low-noise amplifier (LNA).

应用临床路径测算烧冲复合伤病种医疗费用研究

目的： 分析成批烧冲复合伤病员救治的经费使用分布情况,为制订平战时同类伤员救治费用标准提供依据.方法：应用临床路径方法测算烧冲复合伤病种的医疗费用,提出成批伤员救治经费准备标准.结果：成批烧冲复合伤员的伤情复杂、救治难度大、所需医疗费用高,不同时期医疗费用消耗有所差异.     

帕金森病非运动症状与纹状体囊泡单胺转运蛋白2密度的相关性

目的:探讨帕金森病(PD)患者非运动症状(NMSs)和纹状体部位的囊泡单胺转运蛋白2(VMAT2)密度之间的相关性。方法:2018年12月至2019年12月从中山大学附属第一医院共前瞻性招募29名健康受试者[男16名,女13名,年龄(48.8±14.2)岁]和67例PD患者,PD患者包括31例改良Hoehn-Yahr(...     

The effects of parkin suppression on the behaviour, amyloid processing, and cell survival in APP mutant transgenic mice

Parkin suppression induces accumulation of β-amyloid in mutant tau mice. We studied the effect of parkin suppression on behaviour and brain pathology in APP_swe mutant mice. We produced double mutant mice with human mutated APP_swe + partial (hemizygote) or total (homozygote) deletion of Park-2 gene. We studied the development, behaviour, brain histology, and biochemistry of 12- and 16-month-old animals in 6 groups of mice, with identical genetic background: wild-type (WT), APP_swe overexpressing (APP), hemizygote and homozygote deletion of Park-2 (PK^+/− and PK^−/−, respectively), and double mutants (APP/PK^+/− and APP/PK^−/−).APP mice have reduced weight gain, decreased motor activity, and reduced number of entrances and of arm alternation in the Y-maze, abnormalities which were partially or completely normalized in APP/PK^+/− and APP/PK^−/− mice. The double mutants had similar number of mutant human APP transgene copies than the APP and levels of 40 and 80 kDa proteins; but both of them, APP/PK^+/− and APP/PK^−/− mice, had less plaques in cortex and hippocampus than the APP mice. APP mutant mice had increased apoptosis, proapoptotic Bax/Bcl2 ratios, and gliosis, but these death-promoting factors were normalized in APP/PK^+/− and APP/PK^−/− mice. APP mutant mice had an increased number of tau immunoreactive neuritic plaques in the cerebral cortex as well as increased levels of total and phosphorylated tau protein, and these changes were partially normalized in APP/PK^+/− heterozygotic and homozygotic APP/PK^−/− mice. Compensatory protein-degrading systems such as HSP70, CHIP, and macroautophagy were increased in APP/PK^+/− and APP/PK^−/−. Furthermore, the chymotrypsin- and trypsin-like proteasome activities, decreased in APP mice in comparison with WT, were normalized in the APP/PK^−/− mice.We proposed that partial and total suppression of parkin triggers compensatory mechanisms, such as chaperone overexpression and increased autophagy, which improved the behavioural and cellular phenotype of APP_swe mice.