Propofol Reduces Inflammatory Brain Injury after Subarachnoid Hemorrhage: Involvement of PI3K/Akt Pathway

Abstract

Background: Our previous study showed that propofol, one of the widely used anesthetic agents, can attenuate subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) via inhibiting inflammatory and oxidative reaction. However, it is perplexing whether propofol attenuates inflammatory and oxidative reaction through modulating PI3K/Akt pathway. The present study investigated whether PI3K/Akt pathway is involved in propofol's anti-inflammation, antioxidation, and neuroprotection against SAH-induced EBI. Materials and methods: Adult Sprague-Dawley rats underwent SAH and received treatment with propofol or vehicle after 2 and 12 hours of SAH. LY294002 was injected intracerebroventricularly to selectively inhibit PI3K/Akt signaling. Mortality, SAH grading, neurological scores, brain water content, evans blue extravasation, myeloperoxidase, malondialdehyde, superoxide dismutase, and glutathione peroxidase were measured 24 hours after SAH. Immunoreactivity of p-Akt, t-Akt, nuclear factor-kappa B (NF-kB) p65, nuclear factor erythroid-related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase (NQO1), and cyclooxygenase-2 (COX-2) in rat brain was determined by western blot. Tumor necrosis factor-a (TNF-a) and interleukin-1b (IL-1b) in rat brain were examined by ELISA. Results: Propofol significantly reduces neurological dysfunction, BBB permeability, brain edema, inflammation, and oxidative stress, all of which were reversed by LY294002. Propofol significantly upregulates the immunoreactivity of p-Akt, Nrf2, and NQO1, all of which were abolished by LY294002. Propofol significantly downregulates the overexpression of NF-kB p65, COX-2, TNF-a, and IL-1b, all of which were inhibited by LY294002. Conclusion: These results suggest that propofol attenuates SAH-induced EBI by inhibiting inflammatory reaction and oxidative stress, which might be associated with the activation of PI3K/Akt signaling pathway.

FXII regulates the formation of deep vein thrombosis via the PI3K/AKT signaling pathway in mice

“…Numerous studies have indicated that the PI3K/AKT signaling pathway is an important intracellular signaling pathway that plays a role in a variety of cellular physiological processes, including cell proliferation, cell apoptosis and inflammatory response (25)(26)(27). Chang et al reported that 7-ketocholesterol contributed to thrombosis via the induction of endothelial damage, apoptosis and inflammatory responses, which were associated with the activation of PI3K/AKT signaling (28).…”

CXCL-12 Attenuates Neuroinflammation via the CXCR4/PI3K/Akt Signaling Pathway in a Rat Model of SAH

“…Sugawara et al [38] found that intraperitoneal injection of simvastatin reduced nerve dysfunction and cerebral vasospasm in SAH rats, and intravenous injection of wortmannin (PI3K/Akt inhibitor) abolished the neuroprotective effects of simvastatin, which indicated that the PI3K/Akt signaling pathway is involved in the neuroprotective effect of cerebral vasospasm after SAH. Zhang HB et al [39] demonstrated that propofol attenuates SAHinduced EBI by inhibiting in ammation and oxidative stress, which was reversed by LY294002 (PI3K/Akt inhibitor) administration. Furthermore, broblast growth factor-2 alleviated neurological impairments, brain edema, and neuronal apoptosis following SAH.…”

Role of Anesthetics and Their Adjuvants in Neurovascular Protection in Secondary Brain Injury after Aneurysmal Subarachnoid Hemorrhage

“…A follow up study by the same authors showed that intraperitoneal administration of propofol 50 mg/kg at 2 h and repeated at 12 h after SAH in a rat endovascular perforation model reduced cerebral edema, blood–brain barrier permeability and improved neurological scores. Propofol’s EBI protection in this study was reversed by LY294002, a specific inhibitor of Phosphatidylinositol 3-kinase/Akt (PI3K/Akt) signaling pathway, suggesting a possible involvement of PI3K/Akt pathway in propofol’s protection [ 19 ].…”

“…Available experimental and clinical evidence, though somewhat limited in scope, have shown that propofol protects against SAH-induced EBI [ 18 , 19 ]. Whether propofol provides protection against SAH-induced DCI, however, remains unclear.…”