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Biol Psychiatry. 2014 Oct 1;76(7):575-84. doi: 10.1016/j.biopsych.2013.10.014. Epub 2013 Oct 25.

Immune activation promotes depression 1 month after diffuse brain injury: a role for primed microglia.

Author information

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.

KEYWORDS:

Cytokines; depression; fluid percussion injury; lipopolysaccharide; major histocompatibility complex II; microglia

PMID:
24289885
PMCID:
PMC4000292
DOI:
10.1016/j.biopsych.2013.10.014
[Indexed for MEDLINE]
Free PMC Article

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