Noninvasive Vagus Nerve Stimulation Protects Neurons in the Perihematomal Region and Improves the Outcomes in a Rat Model of Intracerebral Hemorrhage

Background: Intracranial hemorrhage (ICH) is a devastating stroke subtype with a high rate of mortality and disability. Therapeutic options available are primarily limited to supportive care and blood pressure control, whereas the surgical approach remains controversial. In this study, we explored the effects of noninvasive vagus nerve stimulation (nVNS) on hematoma volume and outcome in a rat model of collagenase-induced ICH. Methods: Adult male Wistar rats were randomized into two study groups: (1) ICH-treated (rats treated with five 2-min nVNS) and (2) ICH-control (ICH with sham nVNS). Each group received either a 0.1-U or a 0.2-U collagenase dose. After assessing neurological function, rats were euthanized at 24 h for spectrophotometric hemoglobin assay, hematoma volume measurements, and histological studies. Results: The ICH-treated group that received the 0.1-U collagenase dose demonstrated significantly smaller hematoma volume and improved motor function compared with the ICH-control with the same dose. Furthermore, the pooled data for the ICH-treated groups (both 0.1 U and 0.2 U of collagenase) revealed a reduction in neuronal loss in the perihematomal region in the histopathological studies. This effect was not significant for the group that received a 0.2-Ucollagenase dose. Conclusions: nVNS therapy in acute settings may provide a neuroprotective effect and limit hematoma expansion in smaller volumes, improving neurological function post-ICH.