Inhibition of exosome release augments neuroinflammation following intracerebral hemorrhage

Abstract

Intracerebral hemorrhage (ICH) is a devastating disease that constitutes about 10%-15% in all strokes. It has a high mortality and morbidity without effective clinical management. 1 Upon the ictus of ICH, blood components influx into the brain and trigger a cascade of pathological events such as activation of microglia and infiltration of peripheral leukocytes, leading to a burst of production of inflammatory factors. These events exacerbate mass effect, accelerates

Intranasal Delivery of Gene-Edited Microglial Exosomes Improves Neurological Outcomes after Intracerebral Hemorrhage by Regulating Neuroinflammation

“…For depletion of Gr-1 + myeloid cells in vivo, mice were intraperitoneally injected with anti-mouse Gr-1 monoclonal antibody (MAbRB6-8C5; BioXcell, Lebanon, NH, USA) with a dose of 250 μg at 1 day before and 1 day after ICH surgery. In vivo rat IgG2b (LTF-2; BioXcell, Lebanon, NH, USA) was used as isotype control [ 29 , 30 ]. For the verification of Gr-1 + cell depletion, flow cytometry was performed.…”

Novel targets, treatments, and advanced models for intracerebral haemorrhage

“…They are increasingly described in neurodegenerative disease, but knowledge in ICH is limited. Importantly, there is preliminary evidence for exosome-mediated anti-inflammatory mechanisms in mice 87 and humans. 88 Exosomes are frequently derived from mesenchymal stem cells (MSCs) as these cells are known to exert beneficial effects after ICH which are believed to be at least partly mediated by exosomes.…”

Mesenchymal stem cell-derived extracellular vesicles/exosome: A promising therapeutic strategy for intracerebral hemorrhage

“…During the early activation of ICH microglia, both cell death and breakdown products trigger an inflammatory cascade leading to increased neuronal death. ICH induces an extensive neuroinflammatory response, which seems to be responsible for the exaggeration of brain damage [ [49] , [50] , [51] , [52] ]. Therefore, reducing neuroinflammation is regarded as a potential target for therapeutic intervention.…”