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Benusa et al. Neuroimmunol Neuroinflammation 2020;7:23-39 Neuroimmunology
DOI: 10.20517/2347-8659.2019.28 and Neuroinflammation

Review Open Access

Microglial process convergence on axonal segments
in health and disease

Savannah D. Benusa, Audrey D. Lafrenaye

Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Correspondence to: Dr. Audrey D. Lafrenaye, Department of Anatomy and Neurobiology, Virginia Commonwealth University
Medical Center, P.O. Box 980709, Richmond, VA 23298, USA. E-mail: audrey.lafrenaye@vcuhealth.org

How to cite this article: Benusa SD, Lafrenaye AD. Microglial process convergence on axonal segments in health and disease.
Neuroimmunol Neuroinflammation 2020;7:23-39. http://dx.doi.org/10.20517/2347-8659.2019.28

Received: 31 Dec 2019 First Decision: 6 Feb 2020 Revised: 19 Feb 2020 Accepted: 27 Feb 2020 Published: 21 Mar 2020

Science Editor: Jeffrey Bajramovic Copy Editor: Jing-Wen Zhang Production Editor: Tian Zhang

Abstract
Microglia dynamically interact with neurons influencing the development, structure, and function of neuronal networks.
Recent studies suggest microglia may also influence neuronal activity by physically interacting with axonal domains
responsible for action potential initiation and propagation. However, the nature of these microglial process interactions
is not well understood. Microglial-axonal contacts are present early in development and persist through adulthood,
implicating microglial interactions in the regulation of axonal integrity in both the developing and mature central nervous
system. Moreover, changes in microglial-axonal contact have been described in disease states such as multiple sclerosis
(MS) and traumatic brain injury (TBI). Depending on the disease state, there are increased associations with specific
axonal segments. In MS, there is enhanced contact with the axon initial segment and node of Ranvier, while, in TBI,
microglia alter interactions with axons at the site of injury, as well as at the axon initial segment. In this article, we review
the interactions of microglial processes with axonal segments, analyzing their associations with various axonal domains
and how these interactions may differ between MS and TBI. Furthermore, we discuss potential functional consequences
and molecular mechanisms of these interactions and how these may differ among various types of microglial-axonal
interactions.

Keywords: Microglia, multiple sclerosis, traumatic brain injury, microglia-axonal interactions

INTRODUCTION
Microglia are the innate immune cells of the central nervous system (CNS) and the primary mediators
of the neuroinflammatory response. They are derived from a pool of primitive macrophages from the
[1-3]
yolk sac that appear during early embryonic development . Microglia are ontogenetically distinct from

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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