Expanding the Potential Therapeutic Options for Remote Ischemic Preconditioning: Use in Multiple Sclerosis

Carlos R Camara-Lemarroy, Luanne Metz, Eric E Smith, Jeff F Dunn, V Wee Yong, Carlos R Camara-Lemarroy, Luanne Metz, Eric E Smith, Jeff F Dunn, V Wee Yong

No abstract available

Keywords: ischemic preconditioning; multiple sclerosis; neuroimmunology; neuroprotection; remote ischemic preconditioning.

Figures

Figure 1
Figure 1
Possible neuroprotective mechanisms of ReIP in MS and proposed intervention. (A) ReIP can modulate several of the typical pathogenic mechanisms involved in MS. In the periphery, ReIP can alter lymphocyte populations and may also maintain blood brain barrier (BBB) permeability through reduction in matrix metalloproteinases (MMPs) and increases in transforming growth factor beta (TGF-beta). In the central nervous system, ReIP increases the expression of hypoxia inducible factor-1 alpha (HIF1-alpha), heat shock proteins (HSP) and erythropoietin (EPO), conferring neurons and glia protection against inflammatory insults and apoptosis. ReIP also reduces the production of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) and increases levels of anti-inflammatory cytokines such as interleukin (IL)-10. ReIP ameliorates oxidative stress by reducing the production of reactive oxygen species (ROS) and nitric oxide (NO). (B) Patients with relapsing remitting MS (RRMS) or progressive forms of MS could be randomized to receive daily, chronic arm ReIP for 1–2 years or a sham procedure. Relevant outcomes would include relapse rate for RRMS, and for all patients, measures of disability such as the expanded disability status score (EDSS), 25 foot-walking test (25FWT), the 9-hole peg test (9HPT) and measures of cognition. MRI biomarkers looking at lesion load and atrophy as well as plausible biomarkers could be of use as well. T, T-lymphocytes; B, B-lymphocytes; D, dendritic cell; M, microglia; N, neuron; A, astrocyte; O, oligodendrocyte; P, plasma cell; NF-κB, nuclear factor kappa-B.

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