Alpha-lipoic acid (ALA) ameliorates early brain injury after subarachnoid hemorrhage in Sprague-Dawley (SD) rats via inhibiting STING-NLRP3 inflammatory signaling.

Neuroinflammation is intimately associated with poor prognosis in patients with subarachnoid hemorrhage (SAH). Alpha-lipoic acid (ALA), a disulfide antioxidant, has been shown to be neuroprotective in an in vivo model of neurological injury; however, the role of ALA in SAH has never been evaluated. In this study, the Sprague-Dawley rats SAH model was induced by endovascular perforation method. ALA was transplanted intravenously into rats, and SR-717, a stimulator of interferon genes (STING) agonist, was injected intraperitoneally. The effects of ALA on early brain injury were assayed by neurological score, hematoxylin and eosin staining and Nissl staining. Immunohistochemistry staining and Western blotting were used to analyze various proteins. ALA significantly reduced STING- NLRP3 protein expression and decreased cell death, which in turn mitigated the neurobehavioral dysfunction following SAH. Furthermore, coadministration of ALA and SR-717 promoted STING-NLRP3 signaling pathway activation following SAH, which reversed the inhibitory effect of ALA on STING-NLRP3 protein activation and increased the neurological deficits. In conclusion, ALA may be a promising therapeutic strategy for alleviating early brain injury after SAH.

Knockdown of sortilin improves the neurological injury and regional cerebral blood flow in rats after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a severe subtype of stroke. Sortilin protein is elevated in cerebrospinal fluid (CSF) of SAH patients. This study explored the mechanism of sortilin in SAH. SAH model was established by occipital cisternal blood injection. Neurological evaluation was performed on SAH rats using the Gracia scoring system and beam-balance tests. Regional cerebral blood flow (rCBF) and intracranial pressure (ICP) changes were measured using a laser Doppler blood flow monitor and an intraparenchymal Camino ICP probe. The correlation between rCBF changes and neurological deficit was analyzed using the Spearman method. Sortilin protein level in rat cerebral cortex and CSF was detected by Western blot. The Garcia score and beam-balance score of rats at 1, 12, 24, 48, and 72 h after SAH were lowered. Blood clots were observed on the ventral surface of the brain in SAH rats, around Willis ring, and ventral surface of brain stem, but no blood clots were found in the control group. At 1, 12, 24, 48, and 72 h after SAH in rats, the severity of SAH was aggravated, rCBF was decreased, and ICP was increased. The changes of rCBF in rat cerebral cortex at 1 and 72 h after SAH were correlated with the Garcia score. Sortilin was highly expressed in the cerebral cortex and CSF of SAH rats. Knockdown of sortilin improved the neurological injury and rCBF in rats. Sortilin was highly expressed in the cerebral cortex and CSF of SAH rats. Sortilin silencing improved neurological injury and CBF in rats.