title: Interferon-Stimulated Gene 15 Upregulation Precedes the Development of Blood-Brain Barrier Disruption and Cerebral Edema after Traumatic Brain Injury in Young Mice.
abstract: Recent studies show that myosin light chain kinase (MLCK) plays a pivotal role in development of cerebral edema, a known complication following traumatic brain injury (TBI) in children and a contributing factor to worsened neurologic recovery. Interferon-stimulated gene 15 (ISG15) is upregulated after cerebral ischemia and is neuroprotective. The significant role of ISG15 after TBI has not been studied. Postnatal Day (PND) 21 and PND24 mice were subjected to lateral closed-skull injury with impact depth of 2.0 or 2.25 mm. Behavior was examined at 7 d using two-object novel recognition and Wire Hang tests. Mice were sacrificed at 6 h, 12 h, 24 h, 48 h, 72 h, and 7 d. ISG15 and MLCK were analyzed by Western blot and immunohistochemistry, blood-brain barrier (BBB) disruption with Evans Blue (EB), and cerebral edema with wet/dry weights. EB extravasation and edema peaked at 72 h in both ages. PND21 mice had more severe neurological deficits, compared with PND24 mice. PND24 mice showed peak ISG15 expression at 6 h, and PND21 mice at 72 h. MLCK peaked in both age groups at 12 h and co-localized with ISG15 on immunohistochemistry and co-immunoprecipitation. These studies provide evidence, ISG15 is elevated following TBI in mice, preceding MLCK elevation, development of BBB disruption, and cerebral edema.
authors: 1 Neuroscience Center of Excellence, Louisiana State University Health Sciences Center , New Orleans, Louisiana.|2 Children's Hospital of New Orleans, Louisiana State University Health Sciences Center , New Orleans, Louisiana.|3 Department of Pediatrics, Louisiana State University Health Sciences Center , New Orleans, Louisiana.
authors: Janet L
authors: JL
authors: Rossi
authors: 4 Department of Neurosurgery, Louisiana State University Health Sciences Center , New Orleans, Louisiana.
authors: Tracey
authors: T
authors: Todd
authors: 4 Department of Neurosurgery, Louisiana State University Health Sciences Center , New Orleans, Louisiana.
authors: Zachary
authors: Z
authors: Daniels
authors: 1 Neuroscience Center of Excellence, Louisiana State University Health Sciences Center , New Orleans, Louisiana.
authors: Nicolas G
authors: NG
authors: Bazan
authors: 1 Neuroscience Center of Excellence, Louisiana State University Health Sciences Center , New Orleans, Louisiana.|4 Department of Neurosurgery, Louisiana State University Health Sciences Center , New Orleans, Louisiana.
authors: Ludmila
authors: L
authors: Belayev
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D001929:Brain Edema / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016207:Cytokines; C489550:G1p2 protein, mouse; D014452:Ubiquitins; D009219:Myosin-Light-Chain Kinase
keywords: ISG15; MLCK; behavior; cerebral edema; traumatic brain injury; young mice