let-7g counteracts endothelial dysfunction and ameliorating neurological functions in mouse ischemia/reperfusion stroke model

Publication date: Available online 1 February 2020Source: Brain, Behavior, and ImmunityAuthor(s): David L. Bernstein, Sachin Gajghate, Nancy L. Reichenbach, Malika Winfield, Yuri Persidsky, Nathan A. Heldt, Slava RomAbstractStroke is a debilitating disease, accounting for almost 20% of all hospital visits, and 8% of all fatalities in the United States in 2017. Following an ischemic attack, inflammatory processes originating from endothelial cells within the brain microvasculature can induce many toxic effects into the impacted area, from both sides of the blood brain barrier (BBB). In addition to increased BBB permeability, impacted brain microvascular endothelial cells can recruit macrophages and other immune cells from the periphery and can also trigger the activation of microglia and astrocytes within the brain. We have identified a key microRNA, let-7g, which levels were drastically diminished as consequence of transient middle cerebral artery occlusion (tMCAO) in vivo and oxygen-glucose deprivation (OGD) in vitro ischemia/reperfusion conditions, respectively. We have observed that let-7g* liposome-based delivery is capable of attenuating inflammation after stroke, reducing BBB permeability, limiting brain infiltration by CD3+CD4+ T-cells and Ly6G+ neutrophils, lessening microglia activation and neuronal death. These effects consequently improved clinical outcomes, shown by mitigating post-stroke gait asymmetry and extremity motor function. Due to the role of the end...
Source: Brain, Behavior, and Immunity - Category: Neurology Source Type: research