Muscle fatigue resistance during experimental autoimmune encephalomyelitis in rats

Abstract

Background: Muscle weakness and fatigue are important (functional) symptoms in patients with multiple sclerosis (MS) resulting from the pathological events in the central nervous system. Objective: We examined muscle fatigue resistance following the development of acute experimental autoimmune encephalomyelitis (EAE). Methods: Following familiarization (1w) female Lewis rats were divided in a control (CON, n=12) and EAE (n=12) group, the EAE group determined by the injection of purified myelin basic protein in combination with mycobacterium tuberculosis inducing (hind limb) paralytic disease after 12–14d. Approximately 3d after development of maximal clinical signs, fatigue resistance of the foot extensor muscle group (tibialis anterior (TA), extensor digitorum longus (EDL)) was examined using an isokinetic dynamometer and simultaneous stimulation of the common peroneal nerve. Hence, maximal muscle torque was registerd during 120 (3s rest intervals) maximal (1mA, 250ms) isokinetic contractions at 150Hz and 100°/s. Hereafter, TA and EDL were removed for immunohistochemical type I, IIa and IIb muscle fiber cross sectional area (CSA) determination. Results: Maximal muscle torque in CON was 98±14mN declining (p<0.05) to 64±10mN following 120 contractions. In EAE, however, maximal muscle torque remained stable at 53±9mN following 120 contractions. In EDL (preliminary data), type I and IIa CSA did not differ between CON (I:520±53μmxm, IIa:538±58μmxm) and EAE (I:635±78μmxm, IIa:572±73μmxm) animals. Type IIb CSA, however, was lower (p<0.05) in EAE (1163±85μmxm) vs. CON (1461±113μmxm). Similarly, In TA (preliminary data), type I and IIa CSA did not differ between CON (I:643±140μmxm, IIa:692±102μmxm) and EAE (I:753±147μmxm, IIa:696±123μmxm) animals. Type IIb CSA, however, was lower (p<0.05) in EAE (869±133μmxm) vs. CON (1750±208μmxm). Conclusions: EAE decreases maximal muscle torque yet does not affect muscle fatigue resistance. Preliminary data indicate that this might be due to decreased type IIb muscle fiber CSA.