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Home arrow Environment arrow Inflammatory Disorders of the Nervous System: Pathogenesis, Immunology, and Clinical Management
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Abnormal Flow and MS Pathophysiology

While still early in its understanding, abnormal flow and pressure pulsations may also lead to disturbances in vascular endothelial functioning which may contribute to MS pathogenesis and progression as well as forms of vascular dementias. Because MS is associated with increased vessel stiffness [137], there may be a decreased Windkessel component within several vascular components, which lead to an abnormal and potentially inappropriate communication of pressure waves into smaller branches of the brain vasculature than would normally be seen in healthy individuals. Such abnormal pressure phenomena could change endothelial barrier function and endothelial activation, coagulation, and interactions with support cells necessary to maintain barrier and other vascular characteristics. In the setting of chronic neurovascular diseases and other chronic inflammatory phenomena, inflammatory cytokines may impair smooth muscle contractility to dysregulate autoregulation; in the face of hypertension, combined with altered vessel distensibility, autoregulatory failure could also provoke microbleeds. The extent to which this is communicated to the venous side of the circulation is unclear, but could contribute to perivascular stress and venous cuffing as well as Dawson’s fingers. In the setting of Alzheimer’s disease, amyloid-beta may cooperate to provoke similar forms of vascular stress.

Conclusions

While MS is most widely known as an immune-mediated neurodegenerative condition within the human CNS which shows extensive myelin sheath damage and oligodendrocyte injury, these events may occur after or secondary to BBB disturbances which reveal these previously sequestered epitopes to elements of the immune system. Viral and oligodendrocyte protein (MOG, MAG, and PLP) exposure models may recapitulate phases of MS which “break” this barrier and expose BBB antigens normally concealed from the immune system. The progressive, remitting, and relapsing vascular injuries of MS can be observed in contrast enhancing lesions, which are often vascularly associated, appearing, and often resolving. Excessive activation of the CNS microvasculature therefore may support excessive immune cell penetration of the CNS which can lead to repeated waves of immune cell penetration into the CNS with destruction of brain tissue seen in MS. Because suppression of endothelial adhesion molecules and their leukocyte counter-receptors now represents a main approach to MS therapy, future research into additional endothelial contributions may provide novel methods to prevent initiation and block persistence, stimulation, and penetration of immune cells into the MS-inflamed brain.

 
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