TRPM4 channels couple purinergic receptor mechanoactivation and myogenic tone development in cerebral parenchymal arterioles

Cerebral parenchymal arterioles (PAs) have a critical role in assuring appropriate blood flow and perfusion pressure within the brain. They are unique in contrast to upstream pial arteries, as defined by their critical roles in neurovascular coupling, distinct sensitivities to chemical stimulants, and enhanced myogenic tone development. The objective of the present study was to reveal some of the unique mechanisms of myogenic tone regulation in the cerebral microcirculation. Here, we report that in vivo suppression of TRPM4 (transient receptor potential) channel expression, or inhibition of TRPM4 channels with 9-phenanthrol substantially reduced myogenic tone of isolated PAs, supporting a key role of TRPM4 channels in PA myogenic tone development. Further, downregulation of TRPM4 channels inhibited vasoconstriction induced by the specific P2Y4 and P2Y6 receptor ligands (UTPγS and UDP) by 37% and 42%, respectively. In addition, 9-phenanthrol substantially attenuated purinergic ligand-induced membrane depolarization and constriction of PAs, and inhibited ligand-evoked TRPM4 channel activation in isolated PA myocytes. In concert with our previous work showing the essential contributions of P2Y4 and P2Y6 receptors to myogenic regulation of PAs, the current results point to TRPM4 channels as an important link between mechanosensitive P2Y receptor activation and myogenic constriction of cerebral PAs.     

A dual-labeled Annexin A5 is not suited for SPECT imaging of brain cell death in experimental murine stroke

Cell death is one of the pathophysiological hallmarks after stroke. Markers to image cell death pathways in vivo are highly desirable. We previously showed that fluorescently labeled Annexin A5 (AnxA5), which binds specifically to phosphatidylserine (PS) on dead/dying cells, can be used in experimental stroke for monitoring cell death with optical imaging. Here we investigated whether dual-labeled AnxA5 (technetium and fluorescence label) can be used for single-photon emission computed tomography (SPECT) of cell death in the same model. C57Bl6/N mice were subjected to 60-minute middle cerebral artery occlusion (MCAO) and underwent SPECT imaging at 24, 48, and 72 hours afterwards. They were injected intravenously with either PS-binding AnxA5 or the nonfunctional AnxA5 (negative control), labeled with 99mTc and Alexa Fluor 568, respectively. After SPECT imaging, brain sections were cut for autoradiography and fluorescence microscopy. Ethanol-induced cell death in the femur muscle was used as positive control. We detected dual-labeled AnxA5 in the model of ethanol-induced cell death in the femur muscle, but not after MCAO at any time point, either with SPECT or with ex vivo autoradiography or fluorescence microscopy. Dual-labeled AnxA5 appears to be unsuited for visualizing death of brain cells in this MCAO model.     

针灸治疗脑瘫患儿语言障碍的分析

目的：探讨针灸治疗脑瘫患儿语言障碍的研究进展。方法选择2013年1~12月我院收治的脑瘫患儿30例,将这30例患儿随机分成两组,每组15例患儿,分别命名为治疗组和对照组,对照组的15例患儿采取常规语言训练,治疗组的15例患者在采取常规语言训练的基础上,进行针灸治疗,观察两组患儿的临床治疗效果。结果治疗组临床治疗的总有效率为96.8%。对照组临床治疗的总有效率为77.4%。治疗组患儿临床治疗的总有效率明显的高于对照组。两组总有效率比较,差异有统计学意义（P＜0.05）。结论针灸治疗脑瘫患儿的语言障碍具有良好的效果,该种方法值得临床推广。     

Clinicopathologic and molecular features of intracranial desmoplastic small round cell tumors

Desmoplastic small round cell tumors (DSRCTs) are highly aggressive sarcomas that most commonly occur intra‐abdominally, and are defined by EWSR1‐WT1 gene fusion. Intracranial DSRCTs are exceptionally rare with only seven previously reported fusion‐positive cases. Herein, we evaluate the clinical, morphologic, immunohistochemical and molecular features of five additional examples. All patients were male (age range 6–25 years; median 11 years), with four tumors located supratentorially and one within the posterior fossa. The histologic features were highly variable including small cell, embryonal, clear cell, rhabdoid, anaplastic and glioma‐like appearances. A prominent desmoplastic stroma was seen in only two cases. The mitotic index ranged from <1 to 12/10 HPF (median 5). While all tumors showed strong desmin positivity, epithelial markers such as EMA, CAM 5.2 and other keratins were strongly positive in only one, focally positive in two and negative in two cases. EWSR1‐WT1 gene fusion was present in all cases, with accompanying mutations in the TERT promoter or STAG2 gene in individual cases. Given the significant histologic diversity, in the absence of genetic evaluation these cases could easily be misinterpreted as other entities. Desmin immunostaining is a useful initial screening method for consideration of a DSRCT diagnosis, prompting confirmatory molecular testing. Demonstrating the presence of an EWSR1‐WT1 fusion provides a definitive diagnosis of DSRCT. Genome‐wide methylation profiles of intracranial DSRCTs matched those of extracranial DSRCTs. Thus, despite the occasionally unusual histologic features and immunoprofile, intracranial DSRCTs likely represent a similar, if not the same, entity as their soft tissue counterpart based on the shared fusion and methylation profiles.     

The Claustrum in the Squirrel Monkey

The claustrum (CLA) is a subcortical structure that is reciprocally and topographically connected with the cerebral cortex. The complexity of the cerebral cortex varies dramatically across mammals, raising the question of whether there might also be differences in CLA organization, circuitry, and function. Species variations in the shape of the CLA are well documented. Studies in multiple species have identified subsets of neurochemically distinct interneurons; some data suggest species variations in the nature, distribution, and numbers of different neurochemically identified neuronal types. We have studied the CLA in a smooth-brained primate, the squirrel monkey, using Nissl-stained sections and immunohistochemistry. We found that the shape of the CLA is different from that in other primates. We found several different neurochemically defined populations of neurons equally distributed throughout the CLA. Immunoreactivity to GAD_65/67 and GABA_A receptors suggest that GABAergic interneurons provide widespread inhibitory input to CLA neurons. Immunoreactivity to glutamate transporters suggests widespread and overlapping excitatory input from cortical and possibly subcortical sources. Comparison of CLA organization in different species suggests that there may be major species differences both in the organization and in the functions of the CLA. Anat Rec, 303:1439–1454, 2020. © 2019 American Association for Anatomy     

基于近红外光谱分析技术评价运动对老年人认知功能改善的作用

文题释义： 认知老化：增龄性的认知功能减退,成年之后,随着年龄的增加,记忆、注意、推理能力在达到高峰之后,便开始缓慢的下降,抑制无关刺激影响的能力减弱,进入老年之后,认知功能的衰退加快。 运动负荷：包括负荷强度和负荷量。负荷强度是指运动对机体刺激的深度,通常用最大摄氧量百分比或者最大心率百分比来表示;负荷数量是指练习的重复次数,在训练计划中与负荷强度呈反比的关系。 背景：认知老化是增龄性相关的认知功能衰退,临床上目前没有明确的治疗原则可循,进入终末期发展成为认知功能障碍,运动延缓认知老化得到普遍认可。 目的：总结目前基于近红外光谱分析技术评价运动延缓认知老化的进展和不足。 方法：遵循PRISMA指南,由第一作者以“运动,近红外光谱,认知,老年人,组织蛋白酶B,脑源性神经营养因子”为中文检索词,以“exercise,near-infrared spectroscopy,cognition,elderly or older adults,cathepsin B,brain-derived neurotrophic factor”为英文检索词,对PubMed,WOS,CNKI,万方等数据库分别进行检索,对文献中基于近红外光谱技术的运动,老年人的认知功能的文献,保留37篇文献进一步总结分析。 结果与结论：综合目前基于近红外光谱技术分析运动延缓认知老化的研究,证实运动改善不同脑区皮质的激活程度,进而改善认知功能。长期的有氧运动对认知功能改善的效果较短期运动优,更有利于延缓认知老化。其潜在的生理学机制可能在于运动改善大脑的血流灌注,其次运动刺激骨骼肌分泌神经营养因子,促进神经元的生长、存活、增殖。但干预方案无统一标准,诸多环节,如个体差异、不同脑区指标的结合,被试的身体状况(心血管疾病和肺部疾病)的测试程序均有待于进一步完善,提高参数的可靠性和有效性。 ORCID: 0000-0002-1771-5008(王兴) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程