Date of Award

8-29-2011

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience

Abstract

Guillain-Barré Syndrome (GBS) is a debilitating inflammatory autoimmune disease of the peripheral nervous system that is characterized by rapid-onset paraparesis with areflexia progressing to neuromuscular paralysis. The most common form of GBS observed in North America and Europe is acute inflammatory demyelinating polyneuropathy (AIDP). Enhanced infiltration of pro-inflammatory type 1 helper T (Th1) cells into peripheral nerves of AIDP patients leads to demyelination.

Increasing evidence supports exercise as an effective rehabilitative intervention. Exercise attenuates the onset and progression of autoimmune diseases. Whether exercise alters the progression of GBS remains unclear.

In this study, we determined the effects of forced-exercise on development and progression of experimental autoimmune neuritis (EAN), an animal model of AIDP. We report that a moderate regimen of forced-exercise significantly attenuates the severity of EAN in adult male Lewis rats. Rats were randomized to sedentary EAN and forced-exercise EAN groups. Rats assigned to the forced-exercise group were trained on a motorized treadmill for three weeks. Sedentary rats were allowed to explore the treadmill for the same duration without exercise. After three weeks, rats were immunized with complete Freund's adjuvant containing P2 peptide. Sedentary rats developed a monophasic course of EAN. In contrast, rats subjected to forced-exercise exhibited a significantly attenuated course of EAN. Near peak of disease, evoked compound muscle action potential (CMAP) amplitudes were significantly reduced in sedentary rats compared to forced-exercise rats with mild EAN. In contrast, forced-exercise did not protect against deficits in CMAP amplitudes and in sciatic nerve pathology in sedentary and forced-exercise rats with severe EAN. Lymphocytes recovered from the popliteal lymph nodes of forced-exercise EAN rats exhibited increased proliferative response to P2 peptide compared to sedentary EAN controls. The supernatant from those proliferation assays of forced-exercise EAN rats near onset and peak of disease show an increase in the anti-inflammatory cytokine interleukin-10. The percentage of Th1 lymphocytes present in lymph nodes, spleen, and blood of forced-exercise EAN rats were reduced compared with sedentary EAN controls. These data support a protective effect of forced-exercise against the development of EAN by enhancing anti-inflammatory cytokine release and decreasing percentages of pro-inflammatory Th1 lymphocytes.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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