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Molecular Neurobiology

, Volume 56, Issue 7, pp 5202–5228 | Cite as

Microglia Receptors in Animal Models of Traumatic Brain Injury

  • Daniel Younger
  • Madhuvika Murugan
  • Kakulavarapu V. Rama Rao
  • Long-Jun Wu
  • Namas ChandraEmail author
Article

Abstract

Microglia have been implicated as a key mediator of chronic inflammation following traumatic brain injury (TBI). The animal models of TBI vary significantly based on the type of brain injury (focal versus diffuse). This has made it extremely difficult to assess the role of microglia and the window of microglia activation. Hence, the focus of this review is to summarize the time course of microglia activation in various animal models of TBI. The review explores the repertoire of secondary injury mechanisms such as aberrant neurotransmitter release, oxidative stress, blood-brain barrier disruption, and production of pro-inflammatory cytokines that follow microglia activation. Since receptors act as sensors for activation, we highlight certain microglia receptors that have been implicated in TBI pathology, including fractalkine receptor (CX3CR1), purinergic receptor (P2Y12R), Toll-like receptor (TLR4), scavenger receptors, tumor necrosis factor receptor (TNF-1R), interleukin receptor (IL-1R), complement receptors, and peroxisome proliferator-activated receptor (PPAR). In addition to describing their downstream signaling pathways in TBI, we describe the functional consequences of their activation and the implication in behavioral outcomes. Taken together, this review will provide a holistic view of the role of microglia and its receptors in TBI based on animal studies.

Keywords

Microglia Brain injury Receptors 

Abbreviations

Akt

protein kinase B

AP-1

activator protein-1

APP

amyloid precursor protein

Arg-1

arginase-1

ATP

adenosine triphosphate

BBB

blood-brain barrier

CCI

controlled cortical impact/injury

cFPI

central FPI

cIAP-1

cellular inhibitor of apoptosis protein-1

CNS

central nervous system

CR

complement receptor

CX3CR1

chemokine receptor 1

CXCL1

fractalkine

DAMPS

danger associated molecular patterns

EC

endothelial cells

FPI

fluid percussion injury

GOAD

Gila open access database

HAPI

highly aggressively proliferating immortalized

HMGB1

high mobility group box protein 1

HSP

heat shock protein

IL-1R1

interleukin 1 receptor

IL-1β

interleukin 1β

IRAK4

IL-1R associated kinase 4

IRF-3

interferon regulatory factor–3

KO

knockout

LFPI

lateral FPI

LPA

lysophosphatidic acid

LPS

lipopolysaccharide

MAPK

mitogen-activated protein kinase

MIP-1α

macrophage inflammatory protein-1α

mRNA

messenger RNA

NADPH

nicotinamide adenine dinucleotide phosphate

NFκB

nuclear factor-kappa B

NOX

NADPH oxidase

PACAP30

adenylate cyclase-activating polypeptide

PAMPS

pathogens associated molecular patterns

PCR

polymerase chain reaction

PPAR

peroxisome proliferator-activated receptors

RAGE

receptor for advanced glycation end products

RIP

receptor-interacting protein

RNA

ribonucleic acid

RNA-seq

RNA sequencing

RNS

reactive nitrogen species

ROS

reactive oxygen species

STAT

signal transducer and activator of transcription

TBI

traumatic brain injury

TLR4

Toll-like receptor 4

TNF α

tumor necrosis factor α

TNF-R1

TNFα receptor 1

TRADD

TNF receptor-associated death domain

TRAF-2

TNF receptor-associated factor-2

TSPO

translocator protein

WD

weight drop

Notes

Funding Information

This work was supported by funding from the US Army Medical Research and Material Command (W81XWH-15-1-0303), New Jersey Commission for Brain Injury Research (CBIR17PIL020), and Rutgers Brain Health Institute (BHI-RUN-NJIT-2016).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interests.

Supplementary material

12035_2018_1428_MOESM1_ESM.docx (106 kb)
Supplementary Table 1 Microglial receptors and their functional relevance. (DOCX 106 kb)

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of BioengineeringNew Jersey Institute of TechnologyNewarkUSA
  2. 2.Department of NeurologyMayo ClinicRochesterUSA

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