Dexpanthenol and parallel stress-response alterations in the subacute phase after experimental subarachnoid hemorrhage.

backgroundEarly brain injury (EBI) following subarachnoid hemorrhage (SAH) involves a complex interplay of endoplasmic reticulum (ER) stress, mitochondrial dysfunction, oxidative imbalance, neuroinflammation and endothelial dysregulation that collectively shape neuronal vulnerability. Experimental strategies capable of modulating these interconnected stress responses remain incompletely characterized. Dexpanthenol (DEX), a pantothenic acid derivative involved in cellular energy metabolism, has been shown to influence redox balance and inflammatory signaling in experimental brain injury models, but its association with coordinated EBI-related molecular responses after SAH has not been fully explored.

methodsIn this study, adult male Wistar rats were assigned to Sham, DEX, SAH or SAH + DEX groups. SAH was induced by autologous arterial blood injection into the cisterna magna and DEX (500 mg/kg/day, intraperitoneal) was administered for seven consecutive days. Histopathology, immunohistochemistry and RT-qPCR were used to assess neuronal injury, ER stress markers, mitochondrial apoptotic signaling, redox regulation, inflammatory mediators, endothelial regulators and Sirtuin-1 (Sirt1) expression.

resultsSAH was associated with marked neuronal degeneration accompanied by activation of ER stress, apoptotic and inflammatory pathways, endothelial dysregulation and reduced expression of Sirt1 and Glutathione Peroxidase 4 (GPX4). DEX administration was associated with lower expression of ER stress, inflammatory and apoptotic markers, together with partial recovery of GPX4 and a non-significant upward trend in Sirt1 expression, compared with untreated SAH animals.

conclusionThese findings support the view that multiple injury-related pathways remain concurrently altered during the subacute post-hemorrhagic period and are associated with DEX treatment.