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


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.


Microglia Brain injury Receptors 



protein kinase B


activator protein-1


amyloid precursor protein




adenosine triphosphate


blood-brain barrier


controlled cortical impact/injury


central FPI


cellular inhibitor of apoptosis protein-1


central nervous system


complement receptor


chemokine receptor 1




danger associated molecular patterns


endothelial cells


fluid percussion injury


Gila open access database


highly aggressively proliferating immortalized


high mobility group box protein 1


heat shock protein


interleukin 1 receptor


interleukin 1β


IL-1R associated kinase 4


interferon regulatory factor–3




lateral FPI


lysophosphatidic acid




mitogen-activated protein kinase


macrophage inflammatory protein-1α


messenger RNA


nicotinamide adenine dinucleotide phosphate


nuclear factor-kappa B


NADPH oxidase


adenylate cyclase-activating polypeptide


pathogens associated molecular patterns


polymerase chain reaction


peroxisome proliferator-activated receptors


receptor for advanced glycation end products


receptor-interacting protein


ribonucleic acid


RNA sequencing


reactive nitrogen species


reactive oxygen species


signal transducer and activator of transcription


traumatic brain injury


Toll-like receptor 4


tumor necrosis factor α


TNFα receptor 1


TNF receptor-associated death domain


TNF receptor-associated factor-2


translocator protein


weight drop


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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