The Role of Transcutaneous Vagus Nerve Stimulation in Treatment of Acute Brain Injury

Acute brain injury is a major global health problem associated with high mortality and morbidity, limited therapeutic options, prolonged hospital stays, and long-term disability that significantly impairs quality of life and increases healthcare costs. Noninvasive transcutaneous VNS developed as a safer approach for treating cerebral edema, epileptic seizures, and blood-brain barrier disruption, for facilitating the recovery of motoric and cognitive functions, and for immunomodulation. Transcutaneous VNS improves cerebral perfusion pressure and tissue oxygenation, supports reperfusion of the penumbral zone, and reduces neuronal hyperexcitability, thereby suppressing seizures.It may exert anti-inflammatory effects by reducing microglial cytokine and chemokine production. Additionally, vagal stimulation promotes acetylcholine-mediated suppression of pro-inflammatory cytokines, including TNF, IL-1β, IL-6, and IL-18. Another anti-inflammatory mechanism involves ghrelin, a peptide hormone whose serum levels increase under vagal stimulation. Elevated ghrelin reduces TNF-α and other pro-inflammatory cytokines and may limit intracerebral hemorrhage by inhibiting the NLRP3 inflammasome and activating the Nrf2/ARE signaling pathway. Biomarkers such as S100 protein and neuron-specific enolase (NSE) are valuable indicators of brain tissue damage and clinical outcomes; tVNS may reduce their levels and support non-invasive monitoring of disease progression. The technique is considered safe in patients . To date, tVNS has not been evaluated in clinical trials in Croatia, nor reported in case studies or cohort analyses. Study outcomes will be correlated with patients' clinical status, duration and course of hospitalization, complication rates, and overall treatment outcomes.