Restoration of axon conduction and motor deficits by therapeutic treatment with glatiramer acetate.
Bottom Line: The underlying multifactorial anti-inflammatory, neuroprotective effect of GA is in the induction of reactive T cells that release immunomodulatory cytokines and neurotrophic factors at the injury site.These GA-induced cytokines and growth factors may have a direct effect on axon function.Finally, GA improved callosal axon conduction and nodal protein organization in EAE.
Affiliation: Department of Neurology, UCLA School of Medicine, Los Angeles, California.Show MeSH
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Mentions: To assess the functional implications of and build upon the mechanistic insight achieved by cellular and structural assessments of GA-induced CNS improvements, we measured callosal axon conduction in coronal slices from vehicle-treated and therapeutic GA-treated EAE animals (subjects from Fig. 1A experiment, in which treatment was initiated on day 16). Our group has routinely studied axon conduction in brain slices by using an electrophysiological assay to measure local field potential change in response to stimulating a CAP in CC with a square wave current pulse (Crawford et al., 2009b, Patel et al., 2013A). With respect to time, the typical CAP shows two distinct voltage deflections: N1, predominantly from large myelinated axons, and N2, predominantly from smaller non-myelinated axons (Fig. 7A). During EAE, both N1 and N2 CAP amplitudes were decreased to nearly 50% of normal (P < 0.001; Fig. 7A–C). We report significantly increased N1 and N2 CAP amplitudes in GA-treated EAE CC compared with vehicle-treated EAE CC (P < 0.001; Fig. 7A–C). This indicates that GA is neuroprotective of both myelinated and non-myelinated callosal axons. Given our immunohistochemical findings, these functional improvements may be due to a combination of reduced axon loss, increased functional myelination, and reduced axon damage.
Affiliation: Department of Neurology, UCLA School of Medicine, Los Angeles, California.