Dysregulation of long noncoding RNAs (lncRNAs) is associated with abnormal development and pathophysiology in the brain. Increasing evidence has indicated that ischemic stroke is becoming the most common cerebral disease in aging populations. The treatment of ischemic stroke is challenging, due in part to ischemia and reperfusion (I/R) injury. In this study, we revealed that potassium voltage‐gated channel subfamily Q member 1 opposite strand 1 (KCNQ1OT1) was significantly upregulated in ischemic stroke. Knockdown of KCNQ1OT1 remarkably reduced the infarct volume and neurological impairments in transient middle cerebral artery occlusion (tMCAO) mice. Mechanistically, KCNQ1OT1 acted as a competing endogenous RNA of miR‐200a to regulate downstream forkhead box O3 (FOXO3) expression, which is a transcriptional regulator of ATG7. Knockdown of KCNQ1OT1 might inhibit I/R‐induced autophagy and increase cell viability via the miR‐200a/FOXO3/ATG7 pathway. This finding offers a potential novel strategy for ischemic stroke therapy.

Multiple sclerosis (MS) is a chronic autoimmune and degenerative disease of the central nervous system, and conventional treatments have limited efficacy or side effects. Ghrelin, a 28-amino acid octanoylated peptide, has been reported to have neuroprotective effects, including anti-oxidation, anti-inflammation, and anti-apoptosis. Pyroptosis, also called inflammatory cell death, is triggered by overly active inflammasomes and accompanied by the production of numerous cytokines. As immune dysfunction is primarily involved in the pathogenesis of MS, this study aimed to explore the therapeutic effects and precise functional mechanisms of ghrelin against the nod-like receptor protein 3 (NLRP3) inflammasome and pyroptosis in experimental autoimmune encephalomyelitis (EAE). Sprague Dawley rats were immunized with guinea pig spinal cord homogenates and pertussis toxin to develop an EAE model. All rats were randomly divided into four groups: normal control group, EAE group, EAE + ghrelin group, and ghrelin control group. EAE rats showed abnormal behavioral scores and body weight changes. Histologic analysis displayed severe inflammatory infiltration and demyelination in the brain and spinal cord of EAE rats. Ghrelin treatments potently restored these abnormal changes. In addition, the ghrelin-treated EAE group showed significantly downregulated expression of inflammatory cytokines. The expression of proteins involved in the NLRP3 signaling pathway and pyroptosis was decreased as well. We also found that the anti-inflammatory effect of ghrelin was associated with inhibition of nuclear factor (NF)-κB activation. Compared with rats in the healthy control group, rats in the ghrelin control group did not show statistically significant changes in histologic examinations, pro-inflammatory cytokines production, or molecules involved in the NLRP3 signaling pathway, which indicated that ghrelin induced no side effects in the animals of our study. Our findings provide more insight into the use of ghrelin as a novel candidate for MS.