Department of Neurosurgery and Brain Repair, Center of Excellence for Aging and Brain Repair, Morsani College of Medicine, University of South Florida Tampa, FL, USA ; Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida Tampa, FL, USA ; Department of Pathology and Cell Biology, Morsani College of Medicine, University of South Florida Tampa, FL, USA.
Department of Neurosurgery and Brain Repair, Center of Excellence for Aging and Brain Repair, Morsani College of Medicine, University of South Florida Tampa, FL, USA ; Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida Tampa, FL, USA ; Department of Pathology and Cell Biology, Morsani College of Medicine, University of South Florida Tampa, FL, USA ; Department of Psychiatry, Morsani College of Medicine, University of South Florida Tampa, FL, USA.
Front Cell Neurosci. 2014 Feb 3;8:21. doi: 10.3389/fncel.2014.00021. eCollection 2014.
Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease with a complicated and poorly understood pathogenesis. Recently, alterations in the blood-Central Nervous System barrier (B-CNS-B) have been recognized as a key factor possibly aggravating motor neuron damage. The majority of findings on ALS microvascular pathology have been determined in mutant superoxide dismutase (SOD1) rodent models, identifying barrier damage during disease development which might similarly occur in familial ALS patients carrying the SOD1 mutation. However, our knowledge of B-CNS-B competence in sporadic ALS (SALS) has been limited. We recently showed structural and functional impairment in postmortem gray and white matter microvessels of medulla and spinal cord tissue from SALS patients, suggesting pervasive barrier damage. Although numerous signs of barrier impairment (endothelial cell degeneration, capillary leakage, perivascular edema, downregulation of tight junction proteins, and microhemorrhages) are indicated in both mutant SOD1 animal models of ALS and SALS patients, other pathogenic barrier alterations have as yet only been identified in SALS patients. Pericyte degeneration, perivascular collagen IV expansion, and white matter capillary abnormalities in SALS patients are significant barrier related pathologies yet to be noted in ALS SOD1 animal models. In the current review, these important differences in blood-CNS barrier damage between ALS patients and animal models, which may signify altered barrier transport mechanisms, are discussed. Understanding discrepancies in barrier condition between ALS patients and animal models may be crucial for developing effective therapies.
肌萎缩侧索硬化症（ALS）是一种严重的神经退行性疾病，其发病机制复杂且尚未完全阐明。最近，人们认识到血液-中枢神经系统屏障（B-CNS-B）的改变可能是加重运动神经元损伤的一个关键因素。大多数关于 ALS 微血管病理学的发现都是在突变型超氧化物歧化酶（SOD1）啮齿动物模型中确定的，这些发现表明在疾病发展过程中存在屏障损伤，而携带 SOD1 突变的家族性 ALS 患者可能也会出现类似的情况。然而，我们对散发性 ALS（SALS）中 B-CNS-B 功能的了解还很有限。我们最近在 SALS 患者的延髓和脊髓组织的死后灰质和白质微血管中发现了结构和功能的损害，这表明存在普遍的屏障损伤。尽管在 ALS 的突变型 SOD1 动物模型和 SALS 患者中都有许多屏障损伤的迹象（内皮细胞退化、毛细血管渗漏、血管周围水肿、紧密连接蛋白下调和微出血），但其他致病性的屏障改变在 SALS 患者中才被发现。SALS 患者的周细胞退化、血管周围胶原 IV 扩张和白质毛细血管异常是 SALS 患者中重要的与屏障相关的病理学改变，但尚未在 ALS SOD1 动物模型中被注意到。在目前的综述中，讨论了 ALS 患者和动物模型之间血液-中枢神经系统屏障损伤的这些重要差异，这些差异可能表明了改变的屏障转运机制。了解 ALS 患者和动物模型之间的屏障状况差异可能对开发有效的治疗方法至关重要。
