The Role of Microglia in Modulating Neuroinflammation after Spinal Cord Injury

Abstract

The pathobiology of traumatic and nontraumatic spinal cord injury (SCI), including degenerative myelopathy, is influenced by neuroinflammation. The neuroinflammatory response is initiated by a multitude of injury signals emanating from necrotic and apoptotic cells at the lesion site, recruiting local and infiltrating immune cells that modulate inflammatory cascades to aid in the protection of the lesion site and encourage regenerative processes. While peripheral immune cells are involved, microglia, the resident immune cells of the central nervous system (CNS), are known to play a central role in modulating this response. Microglia are armed with numerous cell surface receptors that interact with neurons, astrocytes, infiltrating monocytes, and endothelial cells to facilitate a dynamic, multi-faceted injury response. While their origin and essential nature are understood, their mechanisms of action and spatial and temporal profiles warrant extensive additional research. In this review, we describe the role of microglia and the cellular network in SCI, discuss tools for their investigation, outline their spatiotemporal profile, and propose translationally-relevant therapeutic targets to modulate neuroinflammation in the setting of SCI.

Regulating Endogenous Neural Stem Cell Activation to Promote Spinal Cord Injury Repair

“…Deficits that occur due to SCI include those caused by the initial mechanical damage which results in damage to axons, breakdown of the blood-spinal cord barrier, as well as a cascade of secondary events that worsen the extent of injury [ 1 , 2 , 3 , 4 ]. Secondary events following SCI include vascular damage, inflammation, excitotoxicity, cell death, and the activation of astrocytes [ 2 , 5 , 6 , 7 ]. Combined, these events result in the infiltration of circulatory factors and cellular contents into the spinal cord [ 8 , 9 ].…”

“…Combined, these events result in the infiltration of circulatory factors and cellular contents into the spinal cord [ 8 , 9 ]. Blood-borne macrophages enter the spinal cord and resident microglia react to the injury by releasing cytokines and chemokines (such as IL-1β, IL-6, and TNF-α) resulting in a rapid inflammatory response in the first several weeks following SCI [ 6 , 10 , 11 ]. Additionally, myelin associated factors such as myelin oligodendrocyte glycoprotein (MOG), myelin-associated glycoprotein (MAG), and myelin basic protein (MBP) are released into the cellular milieu [ 12 , 13 ].…”

Regulatory Role of Mesenchymal Stem Cells on Secondary Inflammation in Spinal Cord Injury

“… 55 These cells primarily originate from resident microglia that are activated minutes to hours after SCI, but after 2 days they are mainly from circulating monocytes. 61 These monocyte- and microglia-derived macrophages are still hard to distinguish owing to their similar phenotypes and morphologies. 60 , 62 Based on their phenotypic and functional differences, macrophages can be divided into two main subtypes termed M1 and M2.…”

Repetitive Trans Spinal Magnetic Stimulation Improves Functional Recovery and Tissue Repair in Contusive and Penetrating Spinal Cord Injury Models in Rats

“…These two strategies are based on the knowledge acquired about the cellular and molecular events that take place after SCI. Indeed, at the cellular level, SCI induces a massive inflammation with the infiltration of circulating immune cells, such as macrophages, and induction of microglia reactivity [ 3 ]. At the same time, the initial traumatic injury leads to neuronal and oligodendroglial death [ 2 , 4 ].…”