Master of Science in Biomedical Engineering (MSBME), Wright State University, 2018, Biomedical Engineering

Amyotrophic Lateral Sclerosis (ALS) is a fatal, neurodegenerative disease that is characterized by the death of motoneurons. Life expectancy is only 3-5 years from diagnosis and current treatments only extend survival by 2-3 months. The mechanism of motoneuron death in ALS is still largely unknown, but abnormal motoneuron excitability has been extensively documented. Because the intrinsic excitability of a motoneuron is a defining measure of its normal function, characterizing and regulating motoneuron excitability has become one of the primary aims of ALS research. Although not previously explored in ALS, other clinical applications show the ability of certain electroceutical techniques to modulate the baseline of motor excitability long-term. The aim of this thesis is to determine the plausibility of electroceutical therapy as a technique for regulating motoneuron excitability in ALS by testing its effects on the SOD1-G93A high copy mouse model. Specifically, transcutaneous spinal direct current stimulation (tsDCS) is applied to the lumbar spinal cord of the awake transgenic mice. tsDCS is applied for 30 minutes daily over multiple weeks, beginning at symptom onset. A sham treatment group acts as the control against two stimulation groups: anodal (dorsal-to-ventral field) and cathodal (ventral-to- dorsal field). Treatment effects are measured on weight loss rate, motor function decline, and survival. The data show that our tsDCS protocol was unable to impact disease progression in any of these measures. While this preliminary study shows a lack of promise for electroceutical therapy as an effective ALS treatment, our novel approach of applying long-lasting and noninvasive electrical stimulation on awake mice led to significant technical limitations that may have contributed to the lack of predicted effects. Alternative methods should be considered to address these technical limitations before electroceuticals are concluded ineffective in ALS.

Committee: Sherif Elbasiouny Ph.D., P.E. (Advisor); Mark Rich M.D., Ph.D. (Committee Member); Ulas Sunar Ph.D. (Committee Member) Subjects: Biomedical Engineering; Electrical Engineering; Neurosciences

Doctor of Philosophy, The Ohio State University, 1982, Graduate School

Committee: Not Provided (Other) Subjects: Engineering

Master of Science, University of Akron, 2013, Biomedical Engineering

The impact of electrical stimulation (ES) on growth and regeneration of nerves has been widely studied, with field strength, type of ES, and duration of application all demonstrating impact on the regeneration. However, little information exists directly comparing the frequency of alternating current (AC) stimulation impacts these cell behaviors. This study investigated the biological behavior of chick dorsal root ganglia (DRG): growth of the neurites, spreading of cells from DRG body, cell viability, neurite density and neurite directionality, at 4 frequencies to determine the most efficient frequency with the healthiest neurite growth. E9 chick DRG were stimulated directly with platinum electrodes with AC sinusoidal signals of 2.5Vp-p amplitude and varying frequencies of 20Hz, 200Hz, 1MHz and 20MHz. Characterization of DRG was done using antibody staining. From this study, it can be concluded that application of AC EF increased the length, density and directionality of neurites at low frequencies. Also, application of ES increased cell spreading from the DRG body, which may guide the neurites. Moreover, neurites have greater growth in the high amplitude region of the stimulation chamber (or closer to the anode), indicating that the growth and density is influenced by the voltage intensity. From literature survey, the changes in the biological characteristics of DRG neurites may be due to changes in DRG conductivity.

Committee: Rebecca Willits Dr. (Advisor); Erik Engeberg Dr. (Committee Member); Hossein Tavana Dr. (Committee Member) Subjects: Biomedical Engineering; Biomedical Research; Neurosciences

Master of Sciences, Case Western Reserve University, 2010, EMC - Mechanical Engineering

The goal of this project was to have a prototype of an active Ankle Foot Orthosis (AFO) that would help control and assist plantar flexion and orsiflexion with a single motor acting as an antagonistic pair of uscles. To control the amount and direction of the torque about the ankle Insertion Point Eccentricity Control (IPEC), a way of moving a stored energy, was used. The device, a heavily altered Ankle Foot Orthosis (AFO), would help control and assist plantar flexion and dorsi-flexion. A challenge was also to keep the weight added to the standard AFO at no more than one pound. After initial testing, it was seen that the IPEC AFO is able to provide 3.51 ± .05 Nm about the ankle in dorsi-flexion and 3.88 ± .15 Nm in plantar flexion with a spring modulus of 17.76 lbs/inch and an initial tension of 17.24 lbs. The torque was found to be sufficient to move the foot during walking. The design's most important objective was to be advantageous and safe for the user. The user would range from a Spinal Cord Injury (SCI) subject to a stroke subject with drop-foot or other disorder concerning the ankle. The IPEC AFO cycles quickly enough for an SCI FES user. The IPEC AFO is an improvement because it leverages energy stored in the spring to reduce power required by the motor.

Committee: Roger Quinn PhD (Advisor); Roger Quinn PhD (Committee Chair); Ronald Triolo PhD (Committee Member); Dwight Davy PhD (Committee Member) Subjects: Biomedical Research; Engineering; Mechanical Engineering