Vagus Nerve Stimulation Delivered with Motor Training Enhances Recovery of Function after Traumatic Brain Injury

Abstract

Traumatic Brain Injury (TBI) is one of the largest health problems in the United States, and affects nearly 2 million people every year. The effects of TBI, including weakness and loss of coordination, can be debilitating and last years after the initial injury. Recovery of motor function is often incomplete. We have developed a method using electrical stimulation of the vagus nerve paired with forelimb use by which we have demonstrated enhanced recovery from ischemic and hemorrhagic stroke. Here we have tested the hypothesis that vagus nerve stimulation (VNS) paired with physical rehabilitation could enhance functional recovery after TBI. We trained rats to pull on a handle to receive a food reward. Following training, they received a controlled-cortical impact (CCI) in the forelimb area of motor cortex opposite the trained forelimb, and were then randomized into two treatment groups. One group of animals received VNS paired with rehabilitative therapy, whereas another group received rehabilitative therapy without VNS. Following CCI, volitional forelimb strength and task success rate in all animals were significantly reduced. VNS paired with rehabilitative therapy over a period of 5 weeks significantly increased recovery of both forelimb strength and success rate on the isometric pull task compared with rehabilitative training without VNS. No significant improvement was observed in the Rehab group. Our findings indicate that VNS paired with rehabilitative therapy enhances functional motor recovery after TBI.

Vagus nerve stimulation paired with tactile training improved sensory function in a chronic stroke patient

“…Though as yet unproven, we suspect that the enhanced sensory function in this patient resulted from extensive somatosensory receptive field plasticity, enhanced by the combination of VNS and tactile stimulation (Fig. 3) (Harrison, 2013;Jenkins, 1987;Khodaparast, 2013Pruitt, 2016;Reinecke, 2003;Xerri, 1998).…”

“…Behavioral deficits in animal models of chronic ischemic stroke, intracerebral hemorrhage, and traumatic brain injury improve significantly more when VNS is paired with rehabilitative training compared to rehabilitation alone Khodaparast, 2013Pruitt, 2016). Importantly, VNS provides no benefit when it is delivered two hours after the end of daily rehabilitation .…”

“…VNS is used to reduce seizure frequency in some patients with epilepsy (Howland, 2014) with a 30 seconds on, 5 minutes off stimulation paradigm. Animal research indicates that brief, 0.5 second bursts of 0.8 mA VNS triggers release of norepinephrine and acetylcholine in the cerebral cortex, which can restore synaptic connectivity after brain injury and improve function if delivered during rehabilitative training , 2014, Hulsey, 2016, 2017, Khodaparast, 2013Nichols, 2011;Porter, 2012;Pruitt, 2016). It is not yet known, whether brief bursts of VNS paired with tactile discrimination training can improve the recovery of sensory function after stroke.…”

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

“…Recovery of motor function is associated with plasticity in spared motor circuits [79][80][81], and VNS paired with rehabilitation may enhance this plasticity to support recovery. Pruitt et al [82] evaluated whether VNS therapy could improve recovery of motor function in a controlled cortical impact model of severe TBI. Rats were trained to proficiency on a skilled forelimb task and then received a controlled cortical impact centered on the motor cortex.…”

The gut reaction to traumatic brain injury

“…mice with the hormone ghrelin following TBI blocks the increase in TNF-a and MLCK expression along with the increase in intestinal permeability. 21 Similarly, electrical stimulation of the vagus nerve before TBI in mice, 25,26 increasing glutamine levels in the diet following TBI in rats, 27,28 or injection of the antioxidantsedative propofol following TBI in rats 29 blocks the increase in TNF-a expression as well as the increase in intestinal permeability following TBI. Conversely, mice deficient for nuclear factor erythroid 2-related factor 2 (Nrf2) have higher TNF-a expression and higher intestinal permeability than wild-type mice following TBI.…”