Abstract
Cortical spreading depolarization (SD) waves negatively affect neuronal survival and outcome after ischemic stroke. We here aimed to investigate the effects of vagus nerve stimulation (VNS) on SDs in a rat model of focal ischemia. To this end, we delivered non-invasive VNS (nVNS) or invasive VNS (iVNS) during permanent middle cerebral artery occlusion (MCAO), and found that both interventions significantly reduced the frequency of SDs in the cortical peri-infarct area compared to sham VNS, without affecting relative blood flow changes, blood pressure, heart rate or breathing rate. In separate groups of rats subjected to transient MCAO, we found that cortical stroke volume was reduced 72 h after transient MCAO, whereas stroke volume in the basal ganglia remained unchanged. In rats treated with nVNS, motor outcome was improved 2 days after transient MCAO, but was similar to sham VNS animals 3 days after ischemia. We postulate that VNS may be a safe and efficient intervention to reduce the clinical burden of SD waves in stroke and other conditions.
Highlights
Despite great therapeutic advances in recent years, ischemic stroke remains a major cause of death and disability worldwide, mainly because most therapeutic options are limited to the first hours after stroke onset and are usually performed by highly specialized comprehensive stroke centers
To determine the effects of vagus nerve stimulation (VNS) on spreading depolarization (SD) in a stroke model, we induced focal ischemia by permanent middle cerebral artery occlusion (MCAO) in rats, as this model is characterized by a high rate of SDs during the vessel occlusion time [12]
By measuring relative changes in cortical cerebral blood flow (CBF) using laser speckle contrast imaging through cranial window preparations, we confirmed that the area of interest was located in peri-infarct cortex (Fig 1A–1C)
Summary
Despite great therapeutic advances in recent years, ischemic stroke remains a major cause of death and disability worldwide, mainly because most therapeutic options are limited to the first hours after stroke onset and are usually performed by highly specialized comprehensive stroke centers. There is a clear need to develop novel adjunctive treatment strategies that can be applied and do not interfere with established therapeutic protocols such as thrombolysis and thrombectomy. One such potential intervention is cervical invasive or noninvasive vagus nerve stimulation (VNS), which is an FDA-approved and clinically widely used adjunctive therapy for partial epilepsy, drug-resistant depression and primary headache disorders. VNS has shown beneficial effects on stroke volume and outcome in different animal models of focal ischemia [1,2,3,4,5,6].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
