Neuromodulatory effects of ultrasound stimulation on cervical cord injured rats

Abstract

Spinal cord injury is a devastating neurological condition that affects millions of people worldwide each year. Several neuromodulatory approaches have been applied to restore the function of injured individual, among which neuromodulation therapy has shown most promising results, so far. There is, however, some limitations persist with electrical neuromodulation therapies. Invasive method of spinal cord neuromodulation requires surgeries while non-invasive method shows limited improvements to restore hand function. However, the mechanism is yet unknown. In addition to the electrical and magnetic stimulation, therapeutic effect of ultrasound stimulation on neurons has recently been explored. The non-invasive therapeutic effect of low-intensity pulsed ultrasound is a novel approach that can modulate the neuronal function following a traumatic injury in brain and peripheral nerve. Because of the safety and efficacy low-intensity pulsed ultrasound stimulation has shown promising results in neurorehabilitation. The objective of this thesis was to investigate potential functional effects with ultrasound stimulation in chronic cervical spinal cord injured animal models via behavioural and electrophysiological studies. It was found that, the forelimb reaching and grasping success rate was higher during low-intensity pulsed ultrasound stimulation than without stimulation in rats with cervical cord injury. Furthermore, the rats showed higher grip forces in ultrasound stimulation group compared to the control group. However, the effect is not enough to restore the full forelimb function. Hence, a combinatory neuromodulatory approach was conducted to restore the hand function in cervical cord injured rats. First, a serotonergic agonist drug (Buspirone) with different doses was administered intraperitoneally to find out an optimum dose. The result showed that low doses of serotonergic agonist significant improved forelimb function in rats over high to medium dose group rats. After finding the optimum dose, a combinatory neuromodulatory approach- ultrasound and drug-based treatment was provided to the injured rats and compared to the only stimulation and control groups. The combination group of rats has shown the consistent recovery in the forelimb reaching and grasping task over the control group of rats indicated the potential of the approach. This thesis summarizes the therapeutic effects of low-intensity pulsed ultrasound and serotonergic against neuromodulation on forelimb functional recovery including reaching and grasping after cervical spinal cord injury, and offers a clinical translation of a novel non-invasive neuromodulation therapy for the paralyzed.