Forced Exercise Preconditioning Attenuates Experimental Autoimmune Neuritis by Altering T_h1 Lymphocyte Composition and Egress

Abstract

A short-term exposure to moderately intense physical exercise affords a novel measure of protection against autoimmune-mediated peripheral nerve injury. Here, we investigated the mechanism by which forced exercise attenuates the development and progression of experimental autoimmune neuritis (EAN), an established animal model of Guillain–Barré syndrome. Adult male Lewis rats remained sedentary (control) or were preconditioned with forced exercise (1.2 km/day × 3 weeks) prior to P2-antigen induction of EAN. Sedentary rats developed a monophasic course of EAN beginning on postimmunization day 12.3 ± 0.2 and reaching peak severity on day 17.0 ± 0.3 (N = 12). By comparison, forced-exercise preconditioned rats exhibited a similar monophasic course but with significant (p < .05) reduction of disease severity. Analysis of popliteal lymph nodes revealed a protective effect of exercise preconditioning on leukocyte composition and egress. Compared with sedentary controls, forced exercise preconditioning promoted a sustained twofold retention of P2-antigen responsive leukocytes. The percentage distribution of pro-inflammatory (Th1) lymphocytes retained in the nodes from sedentary EAN rats (5.1 ± 0.9%) was significantly greater than that present in nodes from forced-exercise preconditioned EAN rats (2.9 ± 0.6%) or from adjuvant controls (2.0 ± 0.3%). In contrast, the percentage of anti-inflammatory (Th2) lymphocytes (7–10%) and that of cytotoxic T lymphocytes (∼20%) remained unaltered by forced exercise preconditioning. These data do not support an exercise-inducible shift in Th1:Th2 cell bias. Rather, preconditioning with forced exercise elicits a sustained attenuation of EAN severity, in part, by altering the composition and egress of autoreactive proinflammatory (Th1) lymphocytes from draining lymph nodes.

Attenuation of experimental autoimmune neuritis with locally administered lovastatin‐encapsulating poly(lactic‐co‐glycolic) acid nanoparticles

“…; Calik et al . ). Similarly, depending on disease stage, macrophage subsets (M1, M2) may initiate induction of, or facilitate recovery from, EAN (Kiefer et al .…”

“…The mechanism by which these nanoparticles exert their protective effect is suggested by a reduced presence of CD68 + macrophage and CD4 + T-cell infiltrates in sciatic nerves compared to nerves harvested from empty nanoparticle-treated EAN rats. It is well established that proinflammatory CD8 + and CD4 + T-cell subsets play a penultimate role in the development of both EAN and AIDP/GBS (Zhang et al 2013;Calik et al 2015). Similarly, depending on disease stage, macrophage subsets (M1, M2) may initiate induction of, or facilitate recovery from, EAN Shin et al 2013).…”

“…Five days after administering PLGA nanoparticles, rats were actively induced with EAN as previously described (Sarkey et al 2007;Calik et al 2015). Rats were anesthetized with ketamine (100 mg/kg)-xylazine (5 mg/kg) and 100 lL of a freshly prepared fine-particle emulsion (1 : 1 v/v) containing 100 lg of a synthetic neuritogenic P2 peptide (53-78, Peptide Synthesis Core Facility of the Simpson Querrey Institute, Northwestern University) suspended in sterile saline and incomplete Freund's adjuvant (Sigma-Aldrich) supplemented with 5 mg/mL heat-inactivated Mycobacteria tuberculosis (strain H37Ra; Difco Laboratories, Detroit, MI, USA) was injected into the left hind footpad.…”

Blood nerve barrier permeability enables nerve targeting of circulating nanoparticles in experimental autoimmune neuritis

“…Weights and clinical progression of disease were assessed daily beginning on Day 7. Rats receive a score of 1 (loss of tail tone), 2 (disrupted gait), 3 (mild hemiparesis), 4 (severe paraparesis), or 5 (paraplegia), including increments of 0.5 [24,25].…”