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Research Article| Volume 333, ISSUE 1-2, P88-92, October 15, 2013

Induction of vascular remodeling: A novel therapeutic approach in EAE

      Abstract

      While the pathologic events associated with multiple sclerosis (MS), diffuse axonal injury, cognitive damage, and white matter plaques, have been known for some time, their etiology is unknown and therapeutic efforts are still somewhat disappointing. This may be due to a lack of fundamental knowledge on how to maintain tissue homeostasis and buffer the brain from secondary injury.
      Maintenance of homeostasis in the brain is the result of regulatory adjustments by cellular constituents of the neurovascular unit (pericytes, endothelial cells, astrocytes, and neurons) that include induction of adaptive vascular remodeling. Results from our laboratory and others suggest that aspects of stress induced adaptation are seen in MS and in the murine model of experimental autoimmune encephalomyelitis (EAE), vascular remodeling is ineffective and biometabolic balance is disrupted. In murine white matter, capillary density is 1/2 that observed in gray matter thus disruption of vascular homeostasis will have a profound impact on tissue integrity. We therefore hypothesized that restoration of microvascular angiodynamics would augment tissue plasticity mitigating the extent of secondary injury and sparing cognitive decline in patients with MS. To test this hypothesis, we have performed preclinical studies and characterized changes in angiodynamics in myelin oligodendrocyte glycoprotein (MOG) peptide (35–55)-induced EAE in C57BL/6 mice with or without concomitant exposure to chronic mild low oxygen. We have reported that exposure to chronic mild low oxygen ameliorated clinical disease in EAE. While the mechanisms of protection are unclear, results suggest that normobaric hypoxia stabilizes the stress response, promotes physiological angiogenesis, and is neuroprotective.

      Keywords

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