Potential roles of vagus nerve stimulation on traumatic brain injury: Evidence from in vivo and clinical studies

Traumatic Brain Injury (TBI) is a one of the leading causes of death and disability worldwide. The consequences of TBI can be divided into two stages: 1) the immediate neuronal destruction during the initial trauma, resulting in the primary brain injury and pathophysiologic sequelae, and 2) the secondary brain injury, encompassing mitochondrial dysfunction, inflammation, cellular excitotoxicity, oxidative stress, and cortical edema, resulting in increased intracranial pressure (ICP) with exacerbated brain damage. Although the pathophysiology in TBI has been thoroughly investigated, the effectivity of therapeutic approaches for TBI is still lacking. Vagus nerve stimulation (VNS) has been used for treating medical refractory epilepsy and chronic drug-resistant depression. Several previous studies also demonstrated that VNS has beneficial effects for TBI in animal models and patients. The neuroprotective effects of VNS on TBI are possibly explained through several mechanisms, including a noradrenergic mechanism, anti-inflammatory effects, regulation of neurotransmitters, and attenuation of blood brain barrier breakdown, and brain edema. The aims of this review are to summarize and discuss the current evidence pertinent to the effect of VNS on both primary and secondary brain injury following TBI from both in vivo and clinical studies.