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综述:发育性炎症和血脑屏障功能障碍在神经发育和神经退行性疾病中的作用

Review: Role of developmental inflammation and blood-brain barrier dysfunction in neurodevelopmental and neurodegenerative diseases.

作者信息

Stolp H B, Dziegielewska K M

机构信息

Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.

出版信息

Neuropathol Appl Neurobiol. 2009 Apr;35(2):132-46. doi: 10.1111/j.1365-2990.2008.01005.x. Epub 2008 Dec 11.

Abstract

The causes of most neurological disorders are not fully understood. Inflammation and blood-brain barrier dysfunction appear to play major roles in the pathology of these diseases. Inflammatory insults that occur during brain development may have widespread effects later in life for a spectrum of neurological disorders. In this review, a new hypothesis suggesting a mechanistic link between inflammation and blood-brain barrier function (integrity), which is universally important in both neurodevelopmental and neurodegenerative diseases, is proposed. The role of inflammation and the blood-brain barrier will be discussed in cerebral palsy, schizophrenia, Parkinson's disease, Alzheimer's disease and multiple sclerosis, conditions where both inflammation and blood-brain barrier dysfunction occur either during initiation and/or progression of the disease. We suggest that breakdown of normal blood-brain barrier function resulting in a short-lasting influx of blood-born molecules, in particular plasma proteins, may cause local damage, such as reduction of brain white matter observed in some newborn babies, but may also be the mechanism behind some neurodegenerative diseases related to underlying brain damage and long-term changes in barrier properties.

摘要

大多数神经疾病的病因尚未完全明确。炎症和血脑屏障功能障碍似乎在这些疾病的病理过程中起主要作用。大脑发育过程中发生的炎症性损伤可能会在日后生活中对一系列神经疾病产生广泛影响。在本综述中,我们提出了一个新的假说,该假说表明炎症与血脑屏障功能(完整性)之间存在机制联系,这在神经发育性疾病和神经退行性疾病中都具有普遍重要性。我们将在脑瘫、精神分裂症、帕金森病、阿尔茨海默病和多发性硬化症中讨论炎症和血脑屏障的作用,在这些疾病中,炎症和血脑屏障功能障碍均在疾病的起始和/或进展过程中出现。我们认为,正常血脑屏障功能的破坏导致血液中分子(特别是血浆蛋白)的短暂涌入,可能会造成局部损伤,比如在一些新生儿中观察到的脑白质减少,但这也可能是一些与潜在脑损伤及屏障特性长期变化相关的神经退行性疾病的发病机制。

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