Inhibition of NLRP3 Inflammasome Ameliorates Cerebral Ischemia-Reperfusion Injury in Diabetic Mice

• Published in: Journal of neural transplantation & plasticity Vol. 2018; no. 2018; pp. 1 - 8
• Main Authors: Zhang, Hong-Fei, You, Zhi-Jian, Tao, Tao, Wang, Yong-Wei, Lai, Lu-Ying, Fang, Ying-Ying, Gu, Ruo-Nan, Li, Feng-Xian, Hong, Pu, Xu, Shi-Yuan
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2018; Hindawi; Hindawi Limited; Wiley
• Subjects: Analysis; Animals; Brain Ischemia - complications; Brain Ischemia - metabolism; Brain Ischemia - prevention & control; Cerebral ischemia; Diabetes; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - metabolism; Disease Models, Animal; Glucose; Heterocyclic Compounds, 4 or More Rings - administration & dosage; Inflammasomes - metabolism; Ischemia; Laboratory animals; Male; Medical research; Messenger RNA; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Pathogenesis; Reperfusion injury; Reperfusion Injury - complications; Reperfusion Injury - metabolism; Reperfusion Injury - prevention & control; RNA; Software; Statistical analysis; Streptozocin; Stroke; Stroke - complications; Stroke - metabolism; Sulfones - administration & dosage; Survival analysis; Type 2 diabetes; Variance analysis; Veins & arteries; China; United States > US
• ISSN: 2090-5904; 0792-8483; 1687-5443
• DOI: 10.1155/2018/9163521

Sustained activation of NLRP3 inflammasome is closely related to diabetes and stroke. However, it is unknown whether NLRP3 inflammasome plays an essential role in stroke in diabetes. We aim to investigate the effect and the potential mechanism of NLRP3 inflammasome in diabetic mice with cerebral ischemia-reperfusion injury. A type 2 diabetic mouse model was induced by a high-fat diet and streptozotocin (STZ). Diabetic mice received MCC950 (the specific molecule NLRP3 inhibitor) or vehicle 60 minutes before the middle cerebral artery occlusion (MCAO) and reperfusion. MCC950 reduced the neurological deficit score of 24 h after cerebral ischemia reperfusion and improved the 28-day survival rate of cerebral ischemia-reperfusion injury in diabetic mice. Furthermore, we found that the mRNA transcription levels of NLRP3, IL-1β, and caspase-1 in the core ischemic area were remarkably amplified in diabetic mice with cerebral ischemia-reperfusion injury, whereas this phenomenon was obviously attenuated by MCC950 pretreatment. In conclusion, the NLRP3 inflammasome was involved in the complex diseases of diabetic stroke. MCC950, the NLRP3 specific inhibitor, ameliorated diabetic mice with cerebral ischemia-reperfusion injury and improved the 28-day survival rate during the recovery stage of ischemic stroke.