Intracerebral hemorrhage (ICH) is a disease with high disability and mortality rates. Currently, the efficacy of therapies available for ICH is limited. Microglia-mediated neuroinflammation substantially exacerbates brain damage following ICH. Here, we investigated whether mitochondrial uncouplers conferred protection by suppressing neuroinflammation following ICH. To mimic ICH-induced neuroinflammation in vitro, we treated microglia with red blood cell (RBC) lysate. RBC lysate enhanced the expression of proinflammatory cytokines in microglia. A clinically used uncoupler, niclosamide (Nic), reduced the RBC lysateinduced expression of pro-inflammatory cytokines in microglia. Moreover, Nic ameliorated brain edema, decreased neuroinflammation, and improved neurological deficits in a well-established mouse model of ICH. Like niclosamide, the structurally unrelated uncoupler carbonyl cyanide p-triflouromethoxyphenylhydrazone (FCCP) reduced brain edema, decreased neuroinflammation, and improved neurological deficits following ICH. It has been reported that mitochondrial uncouplers activate AMP-activated protein kinase (AMPK). Mechanistically, Nic enhanced AMPK activation following ICH, and AMPK knockdown abolished the beneficial effects of Nic following ICH. In conclusion, mitochondrial uncouplers conferred protection by activating AMPK to inhibit microglial neuroinflammation following ICH.

Cerebral stroke is caused by the reduction or disruption of the blood supply to the brain, which results in cell death. Currently, the diagnosis of stroke is troublesome and expensive. In this study, samples of peripheral blood from eight male stroke patients and four male healthy controls were collected. RNA-seq of platelets was performed to detect the differential expression of mRNA in platelets isolated from the samples. Totally, 1091 (429 up-regulated and 662 down-regulated) differentially expressed genes were identified in patients with stroke compared with healthy controls. Analyses based on Gene Ontology and the KEGG pathway revealed that most annotated genes were involved in graft-versus-host disease, cell adhesion molecules signaling pathways, inflammation-related pathways, and so on. RNA expression levels of 15 inflammation-related genes were analyzed using qRT-PCR, especially egr2, which acts as a protector against stroke. In brief, RNA-seq analysis of platelets from all the samples indicated novel candidate genes and pathways that had the potential to be applied to clinical molecular diagnosis of stroke. Besides, this study provided insights into the function and underlying mechanism of stroke.