L arginine and radiofrequency electromagnetic field attenuate inflammatory and apoptotic injury after experimental subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) triggers intense neuroinflammatory and apoptotic cascades that contribute to secondary brain injury, delayed cerebral ischemia, and poor neurological outcomes. Inflammatory mediators such as interleukin-6 (IL-6) and signal transducer and activator of transcription 3 (STAT3) amplify oxidative stress and endothelial dysfunction, whereas suppression of the hypoxia-inducible factor-1α (HIF-1α)/endothelial nitric oxide synthase (eNOS)/vascular endothelial growth factor (VEGF) pathway impairs hypoxic adaptation and neuronal survival. L-arginine (L-ARG), a nitric oxide precursor, and radiofrequency electromagnetic field (RF-EMF) therapy each exhibit neuroprotective potential through anti-inflammatory and microcirculatory mechanisms. Adult male Wistar rats were assigned to Control, SAH, SAH + L-ARG, SAH + RF, and SAH + L-ARG + RF groups (n = 8 per group). SAH was induced by autologous arterial blood injection into the cisterna magna, followed by daily treatment with L-ARG (500 mg/kg, p.o.) and/or RF-EMF (27.12 MHz, 30 min/day) for seven days. SAH markedly increased NF-κB, TNF-α, Cas-3, IL-6, and STAT3 expression while suppressing HIF-1α, eNOS, and VEGF transcripts. Combined treatment was associated with the most pronounced improvements across measured molecular markers, including reduced inflammation and apoptosis and normalization of mitochondrial regulators (↓BAX, ↑BCL-2). These findings suggest that combined L-ARG and RF-EMF exposure is associated with attenuation of inflammation and apoptosis-related molecular injury after experimental SAH; however, functional and perfusion-based outcomes are required before therapeutic efficacy can be inferred.