Pub Date : 2016-01-01Epub Date: 2016-10-15DOI: 10.29245/2572.942X/2016/7.1082
Aaron Dadas, Jolewis Washington, Damir Janigro
The brain is a complex system that requires continual regulation of parenchymal pressure, osmolarity, and waste removal for optimal function; despite this, human brain lacks any obvious extension of lymphatic circulation for moderating fluid and waste regulation. We recapitulate herein a recent analysis of proteinaceous waste deposition in the human brain, its observed route of clearance, and the implications of abnormal accumulation along this clearance pathway as a potential mechanism of neurological diseases. This study uncovered an analogous staining pattern of cerebral phosphorylated tau in temporal lobe epilepsy (TLE) and chronic traumatic encephalopathy (CTE). Regardless of the underlying physiopathology, p-tau elimination occurred via circulation through the perivenous space, as predicted by a glymphatic route of clearance. Remarkably, we demonstrated that p-tau is associated with a neurological disease that can develop independent of head trauma, since in both CTE and TLE: 1) Extracellular p-tau followed unidirectional, fluid-driven pathways that led toward the space bordering large (>100 μm diameter) blood vessels; 2) Tau-positive staining occurred within astroglial cells adjacent to blood vessels, which signified transcellular transport of p-tau as a potential secondary efflux route; 3) P-tau frequently appeared clustered within the perivenous space. This waste aggregation bears significant implications in the disruption of interstitial fluid circulation, which may contribute to exacerbation of disease states. A better understanding of waste elimination in the human brain may prove significant as a therapeutic target to improve parenchymal fluid circulation, and consequently, mitigate the hydrostatic, osmotic and oncotic imbalances that often cause or exacerbate brain diseases.
大脑是一个复杂的系统，需要不断调节实质压力、渗透压和废物清除以实现最佳功能；尽管如此，人脑却缺乏明显的淋巴循环延伸来调节体液和废物。我们在本文中概述了最近对人脑中蛋白质废物沉积的分析、观察到的废物清除途径，以及这一清除途径上的异常积聚作为神经系统疾病潜在机制的影响。这项研究发现了颞叶癫痫（TLE）和慢性创伤性脑病（CTE）中大脑磷酸化 tau 的类似染色模式。无论潜在的生理病理机制如何，p-tau都是通过静脉周围空间的血液循环排出体外的，这也是glymphatic清除途径所预测的。值得注意的是，我们证明了p-tau与神经系统疾病有关，而这种疾病的发生可能与头部创伤无关，因为在CTE和TLE中都存在这种情况：1）细胞外p-tau沿着单向的、流体驱动的路径通向大血管（直径大于100微米）周围的空间；2）Tau阳性染色出现在血管附近的星形胶质细胞内，这表明p-tau的跨细胞运输是一种潜在的次级外流途径；3）P-tau经常聚集在血管周围的空间内。这种废物聚集对间质液体循环的破坏具有重要意义，可能会导致疾病状态的恶化。更好地了解人脑中的废物排出情况可能会被证明是一个重要的治疗目标，可改善实质组织液循环，从而缓解往往会导致或加剧脑部疾病的静水压、渗透压和肿瘤失衡。
{"title":"Cerebral Waste Accumulation and Glymphatic Clearance as Mechanisms of Human Neurological Diseases.","authors":"Aaron Dadas, Jolewis Washington, Damir Janigro","doi":"10.29245/2572.942X/2016/7.1082","DOIUrl":"10.29245/2572.942X/2016/7.1082","url":null,"abstract":"<p><p>The brain is a complex system that requires continual regulation of parenchymal pressure, osmolarity, and waste removal for optimal function; despite this, human brain lacks any obvious extension of lymphatic circulation for moderating fluid and waste regulation. We recapitulate herein a recent analysis of proteinaceous waste deposition in the human brain, its observed route of clearance, and the implications of abnormal accumulation along this clearance pathway as a potential mechanism of neurological diseases. This study uncovered an analogous staining pattern of cerebral phosphorylated tau in temporal lobe epilepsy (TLE) and chronic traumatic encephalopathy (CTE). Regardless of the underlying physiopathology, p-tau elimination occurred via circulation through the perivenous space, as predicted by a glymphatic route of clearance. Remarkably, we demonstrated that p-tau is associated with a neurological disease that can develop independent of head trauma, since in both CTE and TLE: 1) Extracellular p-tau followed unidirectional, fluid-driven pathways that led toward the space bordering large (>100 μm diameter) blood vessels; 2) Tau-positive staining occurred within astroglial cells adjacent to blood vessels, which signified transcellular transport of p-tau as a potential secondary efflux route; 3) P-tau frequently appeared clustered within the perivenous space. This waste aggregation bears significant implications in the disruption of interstitial fluid circulation, which may contribute to exacerbation of disease states. A better understanding of waste elimination in the human brain may prove significant as a therapeutic target to improve parenchymal fluid circulation, and consequently, mitigate the hydrostatic, osmotic and oncotic imbalances that often cause or exacerbate brain diseases.</p>","PeriodicalId":16555,"journal":{"name":"Journal of neurology & neuromedicine","volume":"1 7","pages":"15-19"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36789066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号