Evaluation of changes in the locomotion and histology of sciatic nerve following experimental autoimmune encephalomyelitis
Introduction: Involvement of peripheral nerves in the experimental model of multiple sclerosis (MS) is rarely observed. The objective of this study was to investigate the changes in the locomotion in a mouse model of experimental autoimmune encephalomyelitis (EAE) and correlate with histological changes, if any, in the sections of sciatic nerve and lumbar part of spinal cord. Material and Methods: C57BL/6 mice (10 weeks, n = 8) were immunized with single subcutaneous injection of 300 µg of MOG35-55 and 200 µL of complete Freund’s adjuvant (CFA) to produce EAE models. Limp tail with weakness of hindlimb was observed on day 10 and improvement in the weakness was observed on day 20 onwards. Footprint analysis was done to evaluate the impairment in the locomotion on day 0, 5, 10, 15 and 20 of the experiment. Results: One way repeated measure ANOVA found significant reduction in the mean hindlimb stride length on day 10 and 15 (left) and on day 15 and day 20 (right) when compared to mean stride length in day 0 (p<0.05). Histological analysis showed evidence of macrophage infiltration around the dilated blood vessels in the epineurium of sciatic nerve and evidence of damage in the myelinated white matter of lateral funiculus of the lumbar sections of the spinal cord in EAE mice. Conclusion: It is concluded that in mouse model of EAE, the impairment of locomotion due to damage in the lumbar part of spinal cord can be associated with inflammatory changes in the sciatic nerve.
BHASIN, M., WU, M. and TSIRKA, SE. Modulation of microglial/ macrophage activation by macrophage inhibitory factor (TKP) or tuftsin (TKPR) attenuates the disease course of experimental autoimmune encephalomyelitis. BMC Immunology, 2007, vol. 8, n. 1, p. 10. PMid:17634104. http://dx.doi.org/10.1186/1471-2172-8-10.
BRUCK, W. The pathology of multiple sclerosis is the result of focal inflammatory demyelination with axonal damage. Journal of Neurology, 2005, vol. 252, suppl 5, p. v3-v9. PMid:16254699. http://dx.doi.org/10.1007/s00415-005-5002-7.
COURATIER, P., BOUKHRIS, S., MAGY, L., TRAORÉ, H. and VALLAT, J-M. Involvement of the peripheral nervous system in multiple sclerosis. Revue Neurologique, 2004, vol. 160, n. 12, p. 1159-1163. PMid:15602361. http://dx.doi.org/10.1016/S0035-3787(04)71160-1.
DYER, CA. Novel oligodendrocyte transmembrane signaling systems. Investigations utilizing antibodies as ligands. Molecular Neurobiology, 1993, vol. 7, n. 1, p. 1-22. PMid:8391270. http://dx.doi.org/10.1007/BF02780606.
HAGEN, K., MELLGREN, S.I. and BOVIM, G. Myelin diseases affecting both the central and the peripheral nervous system. Tidsskrift for Den norske legeforening, 1998, vol. 118, n. 23, p. 3600-3602.
HARTUNG, HP., KIESEIER, BC. and HEMMER, B. Purely systemically active anti-inflammatory treatments are adequate to control multiple sclerosis. Journal of Neurology, 2005, vol. 252, suppl 5, p. v30-v37. PMid:16254700. http://dx.doi.org/10.1007/s00415-005-5006-3.
HEMMER, B., ARCHELOS, JJ. and HARTUNG, HP. New concepts in the immunopathogenesis of multiple sclerosis. Nature Reviews. Neuroscience, 2002, vol. 3, n. 4, p. 291-301. PMid:11967559. http://dx.doi.org/10.1038/nrn784.
JAVED, A. and REDER, AT. Therapeutic role of beta-interferons in multiple sclerosis. Pharmacology & Therapeutics, 2006, vol. 110, n. 1, p. 35-56. PMid:16229894. http://dx.doi.org/10.1016/j.pharmthera.2005.08.011.
KERSCHENSTEINER, M., STADELMANN, C., BUDDEBERG, BS., MERKLER, D., BAREYRE, FM., ANTHONY, DC., LININGTON, C., BRÜCK, W. and SCHWAB, ME. Targeting experimental autoimmune encephalomyelitis lesions to a predetermined axonal tract system allows for refined behavioral testing in an animal model of multiple sclerosis. American Journal of Pathology, 2004, vol. 164, n. 4, p. 1455-1469. PMid:15039233. http://dx.doi.org/10.1016/S0002-9440(10)63232-4.
PENDER, MP. and SEARS, TA. Involvement of the dorsal root ganglion in acute experimental allergic encephalomyelitis in the Lewis rat. A histological and electrophysiological study. Journal of the Neurological Sciences, 1986, vol. 72, n. 2-3, p. 231-242. PMid:3486944. http://dx.doi.org/10.1016/0022-510X(86)90011-0.
POGORZELSKI, R., BANIUKIEWICZ, E. and DROZDOWSKI, W. Subclinical lesions of peripheral nervous system in multiple sclerosis patients. Neurologia i Neurochirurgia Polska, 2004, vol. 38, n. 4, p. 257-264. PMid:15383952.
ROSBO, NK., HOFFMAN, M., MENDEL, I., YUST, I., KAYE, J., BAKIMER, R., FLECHTER, S., ABRAMSKY, O., MILO, R., KARNI, A. and BEN-NUN, A. Predominance of the autoimmune response to myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis: reactivity to the extracellular domain of MOG is directed against three main regions. European Journal of Immunology, 1997, vol. 27, n. 11, p. 3059-3069. PMid:9394837. http://dx.doi.org/10.1002/eji.1830271144.
SAROVA-PINHAS, I., ACHIRON, A., GILAD, R. and LAMPL, Y. Peripheral neuropathy in multiple sclerosis: a clinical and electrophysiologic study. Acta Neurologica Scandinavica, 1995, vol. 91, n. 4, p. 234-238. PMid:7625146. http://dx.doi.org/10.1111/j.1600-0404.1995. tb06996.x.
SILVA, GA., PRADELLA, F., MORAES, A., FARIAS, A., DOS SANTOS, LM. and DE OLIVEIRA, AL. Impact of pregabalin treatment on synaptic plasticity and glial reactivity during the course of experimental autoimmune encephalomyelitis. Brain and Behavior, 2014, vol. 4, n. 6, p. 925-935. PMid:25365796. http://dx.doi.org/10.1002/brb3.276.
SONG, RB., OLDACH, MS., BASSO, DM., DA COSTA, RC., FISHER, LC., MO, X. and MOORE, SA. A simplified method of walking track analysis to assess short-term locomotor recovery after acute spinal cord injury caused by thoracolumbar intervertebral disc extrusion in dogs. Veterinary Journal, 2016, vol. 210, p. 61-67. PMid:26900008. http://dx.doi.org/10.1016/j.tvjl.2016.01.013.
SWANBORG, RH. Experimental autoimmune encephalomyelitis in rodents as a model for human demyelinating disease. Clinical Immunology and Immunopathology, 1995, vol. 77, n. 1, p. 4-13. PMid:7554482. http://dx.doi.org/10.1016/0090-1229(95)90130-2.