Spinal Motor Neuronal Degeneration After Knee Joint Immobilization in the Guinea Pig

Abstract

Objective This study used a unilateral knee joint immobilization model in adult guinea pigs to test the hypothesis that retrograde degeneration of motor neurons in the spinal cord is the result of attenuation of knee joint activities. Methods A total of 32 adult guinea pigs were used and divided into 8 groups based on the duration of knee joint immobilization. Light microscopic studies of Nissl, nitric oxide synthase immunohistochemistry, horseradish peroxidase, and fast blue were carried out to examine the neurons in the spinal cord. Electron microscopy was also performed to examine the neurons and axons. Results After various periods of knee joint immobilization, a variety of features of motor neuronal degeneration were observed. Specific characteristics included gradual increases in the expressions of neuronal nitric oxide synthase and ultrastructural changes in affected motor neurons including reduction of cell organelles, indentation of the nuclear envelop, and small compact clumps of chromatin in the nuclei. Observation of the peripheral nerve (femoral nerve) also revealed demyelination alterations in some axons innervating the muscles of the knee joint. Interestingly, motor neuronal degenerative changes and demyelination were reversible after the knee joint immobilization was removed and knee joint activity was restored. These findings may assist in further development of models for spinal dysfunction such as the chiropractic subluxation complex. Conclusion We conclude that motor neuronal degeneration in the spinal cord and axons in this study was the result of knee joint immobilization. Increases in motor neuronal nitric oxide-mediated oxidative stress level after reduction of target tissue activity may contribute to the mechanism for degenerative changes in the motor neurons in adult spinal cord of the guinea pig.