Pioglitazone attenuates ischaemic stroke aggravation by blocking PPARγ reduction and inhibiting chronic inflammation in diabetic mice

作者：Yaru Guo, Wenqiang Zuo, Lu Yin, Tingting Gu, Shiquan Wang, Zongping Fang, Bai‐Ren Wang, Hailong Dong, Wugang Hou, Zhiyi Zuo, Jiao Deng · 发表于：European Journal of Neuroscience · 年份：2022 · DOI：10.1111/ejn.15789 · 被引用次数：4 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Peroxisome Proliferator-Activated Receptors、Acute Ischemic Stroke Management

Abstract Diabetes can cause vascular remodelling and is associated with worse outcome after ischaemic stroke. Pioglitazone is a commonly used anti‐diabetic agent. However, it is not known whether pioglitazone use before ischaemia could reduce brain ischaemic injury. Pioglitazone was administered to 5‐week‐old db + or db/db mice. Cerebral vascular remodelling was examined at the age of 9 weeks. Expression of peroxisome proliferator‐activated receptor‐γ (PPARγ), p‐PPARγ (S112 and S273), nucleotide‐binding domain (NOD)‐like receptor protein 3 (Nlrp3), interleukin‐1β (IL‐1β) and tumour necrosis factor‐α (TNF‐α) was evaluated in the somatosensory cortex of mice. Neurological outcome was evaluated 24 h after brain ischaemia. Results showed that early pioglitazone treatment provided a long‐lasting effect of euglycaemia but enhanced hyperlipidaemia in the db/db mice. Diabetic mice exhibited increased vascular tortuosity, narrower middle cerebral artery (MCA) width and IgG leakage in the brain. These changes were blocked by early pioglitazone treatment. In diabetic animals, PPARγ expression was reduced, and p‐PPARγ at S273 but not S112, Nlrp3, IL‐1β and TNF‐α were increased in the somatosensory cortex. PPARγ decrease and Nlrp3 increase were mainly in the neurons of the diabetic brain, which was reversed by early pioglitazone treatment. Pioglitazone attenuated the aggravated neurological outcome after stroke in diabetic mice. But this protective effect was abolished through restoring c...