Electrical stimulation of the vagus nerve protects against cerebral ischemic injury through an anti-inflammatory mechanism

Introduction Ischemic strokes, caused by cerebral artery stenosis or occlusion, lead to a reduction or abrupt interruption of local cerebral blood flow, resulting in anoxia in the arterial territory, secondary vascular endothelial injury, and the initiation of various pathological conditions (Jian et al., 2013; Kim et al., 2013; Wang et al., 2014). With technological advances, the clinical diagnosis of stroke has improved (Hofmann et al., 2012; Ii and Tomimoto, 2013), but therapies are only partially effective. Inflammation is one of the most important pathophysiological processes following ischemic stroke. Pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) can induce inflammation, promote the secretion of other inflammatory mediators, and aggravate ischemic neuronal damage (Mohagheghi et al., 2013). Vagus nerve stimulation (VNS) has long been used to treat various conditions. It was initially used in anti-epileptic therapy, and then for the treatment of Alzheimer’s disease, migraine, traumatic brain injury and neuropathic pain (George et al., 2002; Sjögren et al., 2002; Bohotin et al., 2003; Mauskop, 2005). Recent studies have shown that VNS may also have a neuroprotective effect in ischemic brain injury (Masada et al., 1996b; Miyamoto et al., 2003; Tracey, 2007; Sun et al., 2012). The vagus nerve mediates communication between the central nervous system and the immune system, and activation of the vagus nerve inhibits inflammation (Goehler et al., 1999; Mravec, 2011; Picq et al., 2013). Thus, the vagus nerve is a potential therapeutic target for protecting the brain against damage caused by ischemic stroke. In the present study, we examined the neuroprotective effects of VNS and its impact on inflammatory cytokines in a rat model of cerebral ischemia.