Blood-brain barrier (BBB) damage after ischemia significantly influences stroke outcome. Compound LFHP-1c was previously discovered with neuroprotective role in stroke model, but its mechanism of action on protection of BBB disruption after stroke remains unknown. Here, we show that LFHP-1c, as a direct PGAM5 inhibitor, prevented BBB disruption after transient middle cerebral artery occlusion (tMCAO) in rats. Mechanistically, LFHP-1c binding with endothelial PGAM5 not only inhibited the PGAM5 phosphatase activity, but also reduced the interaction of PGAM5 with NRF2, which facilitated nuclear translocation of NRF2 to prevent BBB disruption from ischemia. Furthermore, LFHP-1c administration by targeting PGAM5 shows a trend toward reduced infarct volume, brain edema and neurological deficits in nonhuman primate

Objective To study the presence of microflammation state in ESRD patients and the relationship between microinflammation state and atherosclerosis. Methods Inflammatory cytokines and carotid artery B ultrasound data of 246 ESRD patients and 43 cases with normal renal function as control were collected. The presence of microflammation state and its relationship to atherosclerosis were studied. Results The levels of inflammatory cytokines(CRP,IL 6,TNF ?)in ESRD patients were mostly in normal range, but still much higher than those in control.According to the level of CRP,the patients were divided into three groups.Significant differences of carotid artery B ultrasound and prevalence of cerebrocardiovasculer events were found between two groups with CRP levels less and higher than 4 mg/L. According to the history of atherosclerosis cerebrocardiovasculer disease,patients were divided into two groups. Levels of CRP, IL 6, TNF ?were higher in patients with cerebrocardiovasculer disease than those in patients without, but still in normal range. Conclusions There is a microinflammation status in ESRD patients. The microinflammation status may be a risk factor of high prevalence and mortality of atherosclerosis related cardiovascular events in ESRD patients.