Lithium reduces cerebral ischemia/reperfusion injury in dexamethasone-treated rats: The role of the PI3K/Akt pathway.

Background: Insufficient blood flow to the brain or loss of vascular integrity and bleeding within the brain tissue can damage neuronal cells and cause stroke. Aim: This study aimed to investigate the possible protective effect of lithium against cerebral ischemia reperfusion injury (CIRI) in dexamethasone-treated rats by focusing on changes in the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) pathway. Methods: Dexamethasone (10 mg/kg) was intraperitoneally injected into Wistar albino rats for 5 days. On the fifth day of the experiment, CIRI was triggered by bilateral carotid artery occlusion for one hour, followed by reperfusion for 1 hour. Three groups were investigated: sham, CIRI, and CIRI + Li groups. Rats in the CIRI + Li group were treated with lithium (50 mg/kg) via intraperitoneal injection 30 minutes before the induction of cerebral ischemia. At the end of the experiment, the serum blood glucose levels and body weights were measured. The levels of malondialdehyde, myeloperoxidase, glutathione, nuclear factor erythroid 2, heme oxygenase-1, and superoxide dismutase and Akt in the cerebral tissue were recorded. PI3K, phosphorylated Akt (Ser473), phosphorylated glycogen synthase kinase 3β (Ser9), and silent mating-type information regulation 2 homolog 1 levels were measured. Furthermore, histopathological and P-Akt (Ser473) immunohistochemical investigations of cerebral tissues were performed. Results: CIRI suppressed the PI3K/Akt pathway and increased oxidative stress markers in dexamethasone-treated rats. Lithium pre-injection ameliorated all pathological changes observed with CIRI and upregulated the PI3K/Akt pathway. Conclusion: Lithium can protect against CIRI even in the presence of metabolic disturbances, such as those induced by high-dose dexamethasone. The ameliorative effects of lithium were associated with PI3K/Akt pathway upregulation and oxidative stress downregulation.