Ashley M Fenn1, John C Gensel2, Yan Huang1, Phillip G Popovich3, Jonathan Lifshitz4, Jonathan P Godbout5. 1. Department of Neuroscience, Ohio State University, Columbus, Ohio. 2. Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, Kentucky. 3. Department of Neuroscience, Ohio State University, Columbus, Ohio; Center for Brain and Spinal Cord Repair, Ohio State University, Columbus, Ohio; Institute for Behavioral Medicine Research, Ohio State University, Columbus, Ohio. 4. Barrow Neurological Institute at Phoenix Children's Hospital, Department of Child Health, University of Arizona, College of Medicine-Phoenix, Phoenix, Arizona. 5. Department of Neuroscience, Ohio State University, Columbus, Ohio; Center for Brain and Spinal Cord Repair, Ohio State University, Columbus, Ohio; Institute for Behavioral Medicine Research, Ohio State University, Columbus, Ohio. Electronic address: jonathan.godbout@osumc.edu.
Abstract
BACKGROUND: Traumatic brain injury (TBI) is associated with a higher incidence of depression. The majority of individuals who suffer a TBI are juveniles and young adults, and thus, the risk of a lifetime of depressive complications is a significant concern. The etiology of increased TBI-associated depression is unclear but may be inflammatory-related with increased brain sensitivity to secondary inflammatory challenges (e.g., stressors, infection, and injury). METHODS: Adult male BALB/c mice received a sham (n = 52) or midline fluid percussion injury (TBI; n = 57). Neuroinflammation, motor coordination (rotarod), and depressive behaviors (social withdrawal, immobility in the tail suspension test, and anhedonia) were assessed 4 hours, 24 hours, 72 hours, 7 days, or 30 days later. Moreover, 30 days after surgery, sham and TBI mice received a peripheral injection of saline or lipopolysaccharide (LPS) and microglia activation and behavior were determined. RESULTS: Diffuse TBI caused inflammation, peripheral cell recruitment, and microglia activation immediately after injury coinciding with motor coordination deficits. These transient events resolved within 7 days. Nonetheless, 30 days post-TBI a population of deramified and major histocompatibility complex II(+) (primed) microglia were detected. After a peripheral LPS challenge, the inflammatory cytokine response in primed microglia of TBI mice was exaggerated compared with microglia of controls. Furthermore, this LPS-induced microglia reactivity 30 days after TBI was associated with the onset of depressive-like behavior. CONCLUSIONS: These results implicate a primed and immune-reactive microglial population as a possible triggering mechanism for the development of depressive complications after TBI.
BACKGROUND:Traumatic brain injury (TBI) is associated with a higher incidence of depression. The majority of individuals who suffer a TBI are juveniles and young adults, and thus, the risk of a lifetime of depressive complications is a significant concern. The etiology of increased TBI-associated depression is unclear but may be inflammatory-related with increased brain sensitivity to secondary inflammatory challenges (e.g., stressors, infection, and injury). METHODS: Adult male BALB/c mice received a sham (n = 52) or midline fluid percussion injury (TBI; n = 57). Neuroinflammation, motor coordination (rotarod), and depressive behaviors (social withdrawal, immobility in the tail suspension test, and anhedonia) were assessed 4 hours, 24 hours, 72 hours, 7 days, or 30 days later. Moreover, 30 days after surgery, sham and TBI mice received a peripheral injection of saline or lipopolysaccharide (LPS) and microglia activation and behavior were determined. RESULTS: Diffuse TBI caused inflammation, peripheral cell recruitment, and microglia activation immediately after injury coinciding with motor coordination deficits. These transient events resolved within 7 days. Nonetheless, 30 days post-TBI a population of deramified and major histocompatibility complex II(+) (primed) microglia were detected. After a peripheral LPS challenge, the inflammatory cytokine response in primed microglia of TBI mice was exaggerated compared with microglia of controls. Furthermore, this LPS-induced microglia reactivity 30 days after TBI was associated with the onset of depressive-like behavior. CONCLUSIONS: These results implicate a primed and immune-reactive microglial population as a possible triggering mechanism for the development of depressive complications after TBI.
Authors: Ashley M Fenn; Christopher J Henry; Yan Huang; Allison Dugan; Jonathan P Godbout Journal: Brain Behav Immun Date: 2011-10-17 Impact factor: 7.217
Authors: Colm Cunningham; Suzanne Campion; Katie Lunnon; Carol L Murray; Jack F C Woods; Robert M J Deacon; J Nicholas P Rawlins; V Hugh Perry Journal: Biol Psychiatry Date: 2008-09-18 Impact factor: 13.382
Authors: Dustin J Donnelly; John C Gensel; Daniel P Ankeny; Nico van Rooijen; Phillip G Popovich Journal: J Neurosci Methods Date: 2009-04-23 Impact factor: 2.390
Authors: Angela W Corona; Diana M Norden; John P Skendelas; Yan Huang; Jason C O'Connor; Marcus Lawson; Robert Dantzer; Keith W Kelley; Jonathan P Godbout Journal: Brain Behav Immun Date: 2012-08-19 Impact factor: 7.217
Authors: Carol Murray; David J Sanderson; Chris Barkus; Robert M J Deacon; J Nicholas P Rawlins; David M Bannerman; Colm Cunningham Journal: Neurobiol Aging Date: 2010-05-14 Impact factor: 4.673
Authors: Kristina G Witcher; Chelsea E Bray; Titikorn Chunchai; Fangli Zhao; Shane M O'Neil; Alan J Gordillo; Warren A Campbell; Daniel B McKim; Xiaoyu Liu; Julia E Dziabis; Ning Quan; Daniel S Eiferman; Andy J Fischer; Olga N Kokiko-Cochran; Candice Askwith; Jonathan P Godbout Journal: J Neurosci Date: 2021-01-15 Impact factor: 6.167
Authors: Corina O Bondi; Bridgette D Semple; Linda J Noble-Haeusslein; Nicole D Osier; Shaun W Carlson; C Edward Dixon; Christopher C Giza; Anthony E Kline Journal: Neurosci Biobehav Rev Date: 2014-12-10 Impact factor: 8.989