title: Vasopressin amplifies the production of proinflammatory mediators in traumatic brain injury.
abstract: Arginine vasopressin (AVP) has previously been shown to promote disruption of the blood-brain barrier, exacerbate edema, and augment the loss of neural tissue in various forms and models of brain injury. However, the mechanisms underlying these AVP actions are not well understood. These mechanisms were studied in AVP-deficient Brattleboro rats (Avp(di/di)), and their parental Long-Evans strain, using a controlled cortical impact model of traumatic brain injury (TBI). The increased influx of inflammatory cells into the injured cortex in wild-type versus Avp(di/di) rats was associated with higher levels of cortical synthesis of the CXC and CC chemokines found in wild-type versus Avp(di/di) rats. These chemokines were predominantly produced by the cerebrovascular endothelium and astrocytes. In astrocyte and brain endothelial cell cultures, AVP acted synergistically with tumor necrosis factor-alpha (TNF-alpha) to increase the TNF-alpha-dependent production of CXC and CC chemokines. These AVP actions were mediated by c-Jun N-terminal kinase (JNK), as shown by Western blotting and pharmacological inhibition of JNK activity. The activity of JNK was increased in response to injury, and the differences in the magnitude of its post-traumatic activation between Avp(di/di) and wild-type rats were observed. These data demonstrate that AVP plays an important role in exacerbating the brain inflammatory response to injury.
authors.affiliation: Department of Emergency Medicine, The Warren Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA. Joanna_Szmydynger-Chodobska@brown.edu
authors.forename: Joanna
authors.initials: J
authors.lastname: Szmydynger-Chodobska
authors.forename: Leora M
authors.initials: LM
authors.lastname: Fox
authors.forename: Kirsten M
authors.initials: KM
authors.lastname: Lynch
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Zink
authors.forename: Adam
authors.initials: A
authors.lastname: Chodobski
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D054360:Chemokine CXCL1 / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000378:metabolism; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D018836:Inflammation Mediators / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D051381:Rats; D011910:Rats, Brattleboro; D020318:Rats, Long-Evans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014667:Vasopressins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*
chemical_list: D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D014667:Vasopressins; D048031:JNK Mitogen-Activated Protein Kinases