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The innate immune response plays a role in neuroinflammation following <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content> injury via activation of multiprotein complexes termed inflammasomes that regulate the activation of caspase 1 and the processing of the pro\u2010inflammatory cytokines <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2 and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201018. We report here that the expression of components of the nucleotide\u2010binding and oligomerization domain (NOD)\u2010like receptor protein\u20101 (<jats:styled-content style=\"fixed-case\">NLRP<\/jats:styled-content>\u20101) inflammasome, apoptosis speck\u2010like protein containing a caspase recruitment domain (<jats:styled-content style=\"fixed-case\">ASC<\/jats:styled-content>), and caspase 1 are significantly elevated in spinal cord motor neurons and cortical neurons after <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content> trauma. Moreover, <jats:styled-content style=\"fixed-case\">NLRP<\/jats:styled-content>1 inflammasome proteins are present in exosomes derived from <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content> of <jats:styled-content style=\"fixed-case\">SCI<\/jats:styled-content> and traumatic brain\u2010injured patients following trauma. To investigate whether exosomes could be used to therapeutically block inflammasome activation in the <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content><jats:italic>,<\/jats:italic> exosomes were isolated from embryonic cortical neuronal cultures and loaded with short\u2010interfering <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> (si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>) against <jats:styled-content style=\"fixed-case\">ASC<\/jats:styled-content> and administered to spinal cord\u2010injured animals. Neuronal\u2010derived exosomes crossed the injured blood\u2013spinal cord barrier, and delivered their cargo <jats:italic>in vivo,<\/jats:italic> resulting in knockdown of <jats:styled-content style=\"fixed-case\">ASC<\/jats:styled-content> protein levels by approximately 76% when compared to <jats:styled-content style=\"fixed-case\">SCI<\/jats:styled-content> rats treated with scrambled si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>. Surprisingly, si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> silencing of <jats:styled-content style=\"fixed-case\">ASC<\/jats:styled-content> also led to a significant decrease in caspase 1 activation and processing of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2 after <jats:styled-content style=\"fixed-case\">SCI<\/jats:styled-content>. These findings indicate that exosome\u2010mediated si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> delivery may be a strong candidate to block inflammasome activation following <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content> injury.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13036-fig-0005-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><jats:p>We propose the following signaling cascade for inflammasome activation in peripheral tissues after CNS injury: CNS trauma induces inflammasome activation in the nervous system and secretion of exosomes containing inflammasome protein cargo into cerebral spinal fluid. The inflammasome containing exosomes then fuse with target cells to activate the innate immune response in peripheral tissues. We suggest that these findings may be used to develop new therapeutics to treat the devastating inflammation and cell destruction evoked by CNS injuries. IL\u20101\u03b2 and IL\u201018\u00a0=\u00a0pro\u2010inflammatory cytokines.<\/jats:p>","DOI":"10.1111\/jnc.13036","type":"journal-article","created":{"date-parts":[[2015,1,27]],"date-time":"2015-01-27T12:54:01Z","timestamp":1422363241000},"page":"39-48","source":"Crossref","is-referenced-by-count":203,"title":["Exosome\u2010mediated inflammasome signaling after central nervous system injury"],"prefix":"10.1111","volume":"136","author":[{"given":"Juan Pablo","family":"de Rivero Vaccari","sequence":"first","affiliation":[{"name":"Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of Medicine Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Frank","family":"Brand","sequence":"additional","affiliation":[{"name":"Departments of Physiology and Biophysics University of Miami Miller School of Medicine Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Adamczak","sequence":"additional","affiliation":[{"name":"Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of Medicine Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie W.","family":"Lee","sequence":"additional","affiliation":[{"name":"Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of Medicine Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Perez\u2010Barcena","sequence":"additional","affiliation":[{"name":"Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of Medicine Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Y.","family":"Wang","sequence":"additional","affiliation":[{"name":"Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of Medicine Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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