BACKGROUND: Accumulated evidences have established that inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Sulindac is well known as a nonsteroidal anti-inflammatory drug. However, little is known regarding the effect of sulindac in acute cerebral ischemia. Here, we designed this study to investigate the potential protective effects of sulindac in focal cerebral ischemia and the mechanisms underlying in vivo. METHODS: Focal cerebral ischemia was induced in male Sprague-Dawley rats by permanent middle cerebral artery occlusion (pMCAO). Sulindac was administrated at dose of 4, 10, or 20mg/kg at 30 min before the operation. Neurological deficit scores, brain water content and infarct volumes were measured at 24h after pMCAO. Immunohistochemistry, western blot and reverse transcription-polymerase chain reaction were used for examining the mediators involved in Wnt/β-catenin signaling pathway, including the positive regulators dishevelled (Dvl) and β-catenin, the negative regulators adenomatous polyposis coli (APC), and P-β-catenin, as well as the downstream targets Bcl-2, Bax and claudin-5. RESULTS: Compared with Vehicle group, 20mg/kg sulindac reduced neurological deficits, brain water content and infarct volumes. The same dose of sulindac upregulated the expression of Dvl, β-catenin, Bcl2 and claudin-5, and downregulated APC, P-β-catenin and Bax compared with Vehicle group. CONCLUSIONS: These results showed that sulindac had a significant beneficial effect in cerebral ischemia; this effect may be correlated with the activation of the Wnt/β-catenin signaling.
BACKGROUND: Accumulated evidences have established that inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Sulindac is well known as a nonsteroidal anti-inflammatory drug. However, little is known regarding the effect of sulindac in acute cerebral ischemia. Here, we designed this study to investigate the potential protective effects of sulindac in focal cerebral ischemia and the mechanisms underlying in vivo. METHODS:Focal cerebral ischemia was induced in male Sprague-Dawley rats by permanent middle cerebral artery occlusion (pMCAO). Sulindac was administrated at dose of 4, 10, or 20mg/kg at 30 min before the operation. Neurological deficit scores, brain water content and infarct volumes were measured at 24h after pMCAO. Immunohistochemistry, western blot and reverse transcription-polymerase chain reaction were used for examining the mediators involved in Wnt/β-catenin signaling pathway, including the positive regulators dishevelled (Dvl) and β-catenin, the negative regulators adenomatous polyposis coli (APC), and P-β-catenin, as well as the downstream targets Bcl-2, Bax and claudin-5. RESULTS: Compared with Vehicle group, 20mg/kg sulindac reduced neurological deficits, brain water content and infarct volumes. The same dose of sulindac upregulated the expression of Dvl, β-catenin, Bcl2 and claudin-5, and downregulated APC, P-β-catenin and Bax compared with Vehicle group. CONCLUSIONS: These results showed that sulindac had a significant beneficial effect in cerebral ischemia; this effect may be correlated with the activation of the Wnt/β-catenin signaling.
Authors: Shailaja Kesaraju Allani; Ramanjaneyulu Rayala; Oscar Rivera; Howard M Prentice; Xi Chen; Veronica Ramírez-Alcántara; Joshua Canzoneri; Janet Menzie-Suderam; Xupei Huang; Constantin Georgescu; Jonathan D Wren; Gary A Piazza; Herbert Weissbach Journal: J Pharmacol Exp Ther Date: 2022-06-09 Impact factor: 4.402