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Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease with a complicated and poorly understood pathogenesis. Strong evidence indicates impairment of all neurovascular unit components including the blood-brain and blood-spinal cord barriers (BBB/BSCB) in both patients and animal models. The present review provides an updated analysis of the microvascular pathology and impaired BBB/BSCB in ALS. Based on experimental and clinical ALS studies, the roles of cellular components, cell interactions, tight junctions, transport systems, cytokines, matrix metalloproteinases, and free radicals in the BBB/BSCB disruption are discussed. The impact of BBB/BSCB damage in ALS pathogenesis is a novel research topic, and this review will reveal some aspects of microvascular pathology involved in the disease and hopefully engender new therapeutic approaches., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease with a complicated pathogenesis. Compelling evidence indicates impairment of all neurovascular unit components including the blood-brain and blood-spinal cord barriers (BBB/BSCB) in both patients and animal models, leading to classification of ALS as a neurovascular disease. The present review provides an updated analysis of the normal and impaired BBB/BSCB, focusing on the ALS-altered barrier. Here we describe the roles of cellular components, tight junctions, transport systems, cell interactions, cytokines, matrix metalloproteinases, and free radicals in the BBB/BSCB disruption, along with recent evidence from experimental and clinical ALS studies. The BBB/BSCB is a promising research area in ALS and this review will reveal some aspects of microvascular pathology in ALS and hopefully provide ideas for the development of new therapeutic strategies., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Sanfilippo syndrome type B (MPS III B) is caused by a deficiency of α-N-acetylglucosaminidase enzyme, leading to accumulation of heparan sulfate within lysosomes and eventual progressive cerebral and systemic multiple organ abnormalities. However, little is known about the competence of the blood-brain barrier (BBB) in MPS III B. BBB dysfunction in this devastating disorder could contribute to neuropathological disease manifestations., Methodology/principal Findings: In the present study, we investigated structural (electron microscope) and functional (vascular leakage) integrity of the BBB in a mouse model of MPS III B at different stages of disease, focusing on brain structures known to experience neuropathological changes. Major findings of our study were: (1) endothelial cell damage in capillary ultrastructure, compromising the BBB and resulting in vascular leakage, (2) formation of numerous large vacuoles in endothelial cells and perivascular cells (pericytes and perivascular macrophages) in the large majority of vessels, (3) edematous space around microvessels, (4) microaneurysm adjacent to a ruptured endothelium, (6) Evans Blue and albumin microvascular leakage in various brain structures, (7) GM3 ganglioside accumulation in endothelium of the brain microvasculature., Conclusions/significance: These new findings of BBB structural and function impairment in MPS III B mice even at early disease stage may have implications for disease pathogenesis and should be considered in current and future development of treatments for MPS III B.

Background: Amyotrophic Lateral Sclerosis (ALS) treatment is complicated by the various mechanisms underlying motor neuron degeneration. Recent studies showed that the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) are compromised in an animal model of ALS due to endothelial cell degeneration. A later study demonstrated a loss of endothelium integrity in the spinal cords of ALS patients. Since circulating endothelial cells (CECs) in the peripheral blood are associated with endothelium damage, being detached dysfunctional endothelial cells, we hypothesized that CEC levels may reflect endothelium condition in ALS patients., Methodology/principal Findings: CEC levels were estimated in whole blood smears from ALS patients with moderate stage ((M)ALS), severe stage ((S)ALS), and healthy controls by CD146 expression using immunocytochemistry. A significant reduction of CECs was detected in (M)ALS and (S)ALS patients., Conclusions/significance: CECs did not predict endothelium state in ALS patients; however, endothelial damage and/or impaired endothelium repair may occur in ALS leading to BBB/BSCB dysfunction. Reduced CECs in peripheral blood of ALS patients may indicate different mechanisms of endothelial damage and repair, rather than only detachment of dysfunctional endothelial cells. Although a potential mechanism of CEC reduction is discussed, establishing a reliable indicator of endothelial dysfunction/damage is important for evaluation of BBB/BSCB status in ALS patients during disease progression.