Date of Degree

9-2017

Document Type

Dissertation

Degree Name

Ph.D.

Program

Biology

Advisor(s)

Zaghloul Ahmed

Committee Members

Andrzej Wieraszko

Alejandra Alonso

John Martin

Bassem El-Khodor

Subject Categories

Behavioral Neurobiology | Molecular and Cellular Neuroscience | Other Neuroscience and Neurobiology | Systems Neuroscience

Keywords

Spinal Cord Injury

Abstract

Central nervous system injuries usually produce motor impairments that are exacerbated by pathologically altered muscle tone. Abnormal muscle tone interferes with voluntary movement and is associated with loss of dexterity. Prior work in our laboratory demonstrated that 30-second trans-spinal direct current (DC) stimulation can temporarily modify muscle tone in anesthetized spastic mice after spinal cord injury (SCI). These experiments described DC-induced muscle tone responses to be polarity-dependent. That is, anodal stimulation (current passed from the lumbar spine to sciatic nerve) decreased muscle tone, and cathodal stimulation (current passed from the sciatic nerve to the lumbar spine) increased it. The present study investigates the therapeutic potential of noninvasive trans-spinal DC stimulation (tsDCS) to modulate spasticity in awake mice with SCI. The study aims to investigate the following: 1- The effects of short-term tsDCS and repeated-sessions of tsDCS on muscle tone and on skilled and unskilled locomotion. 2- The long-term modulatory effects of tsDCS on the stretch reflex of the triceps surae muscle (TS), using the rate-dependent depression (RDD) of Hoffmann’s reflex. 3- The changes in muscle tone as a result of combining tsDCS with several pharmacological agents, including gabapentin, morphine and MK-801. To assess spasticity in the awake SCI mouse model, an innovative computer-controlled stretch apparatus with a mouse holder was designed and constructed in our laboratory. The design permitted spasticity assessment by stretching the TS at different speeds, while the animal received noninvasive tsDCS treatment. The treatment protocol consisted of seven consecutive daily tsDCS sessions (20 min/day), followed by spasticity evaluations for four weeks after stimulation ended. The mice were also evaluated for two different types of locomotion: 1- unskilled locomotion using the DigiGait treadmill system, and 2- skilled locomotion using a computer-controlled ladder wheel, constructed in our laboratory. Results show that anodal tsDCS significantly reduced several indices of spasticity during treatment, and for at least four weeks after simulation ended. Additionally, anodal-tsDCS treated animals exhibited significantly improved unskilled and skilled locomotion, and significant increase in RDD. Anodal treatment also improved the spasticity-reducing effects of gabapentin and MK-801, and decreased morphine-induced rigidity. In conclusion, these results show anodal tsDCS to be therapeutically effective in ameliorating SCI-induced spasticity in mice when used alone, or in combination with gabapentin or MK-801.

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