LncRNA NKILA relieves astrocyte inflammation and neuronal oxidative stress after cerebral ischemia/reperfusion by inhibiting the NF-κB pathway

Ischemic stroke is one of the major diseases of the cerebral vasculature. Currently, Ischemic stroke is the leading cause of neurological disability worldwide and has a high morbidity and mortality rate. The NF-κB interacting lncRNA (NKILA), the recently identified, is a key booster of NF-κB pathway. Accumulating studies have shown that NKILA plays a cancer suppressor in a variety of malignancies by regulating the NF-κB pathway. Nevertheless, the role of NKILA in ischemic stroke remains to be elucidated.We constructed a mouse model of middle cerebral artery occlusion-reperfusion (MCAO/R). TTC staining and dry and wet weight method were used to evaluate infarction and water content of brain tissue. RT-qPCR was performed to detect NKILA expression in cerebral infarction tissues. After labeling astrocytes and neurons with GFAP and NeuN, respectively, EDU and TUNEL staining were performed. Inflammatory factor levels were detected by ELISA. Commercial kits were used to detect the levels of oxidative stress-related factors. In in vitro, the HT22/U251 cell co-culture model was used for oxygen-glucose deprivation and re-introduction (OGD/R) to verify the effect of NKILA on neuronal cell inflammation and oxidative stress through astrocytes.In in vivo experiments, NKILA significantly reduced cerebral infarction volume, brain water content and neurological score caused by MCAO/R. Moreover, NKILA blocked the activation of the NF-κB pathway, and inhibited astrocyte proliferation and neuron apoptosis as well as inflammation and oxidative stress. In in vitro experiments, NKILA significantly inhibited NF-κB pathway in HT22 cells. In addition, NKILA alleviated the inflammatory response and oxidative stress of U251 cells mediated by HT22 cells after OGD/R, and promoted U251 cell proliferation and inhibit their apoptosis.In summary, we found for the first time that NKILA alleviates inflammatory response and oxidative stress after cerebral ischemia/reperfusion by blocking the activation of NF-κB pathway.