Abstract
Although the increased expression of members of the chondroitin sulfate proteoglycan family, such as neuron-glial antigen 2 (NG2), have been well documented after an injury to the spinal cord, a complete picture as to the cellular origins and function of this NG2 expression has yet to be made. Using a spinal cord injury (SCI) mouse model, we describe that some infiltrated bone marrow-derived macrophages (BMDMΦ) are early contributors to NG2/CSPG4 expression and secretion after SCI. We demonstrate for the first time that a lesion-related form of cellular debris generated from damaged myelin sheaths can increase NG2/CSPG4 expression in BMDMΦ, which then exhibit enhanced proliferation and decreased phagocytic capacity. These results suggest that BMDMΦ may play a much more nuanced role in secondary spinal cord injury than previously thought, including acting as early contributors to the NG2 component of the glial scar.
Highlights
Spinal cord injury (SCI) is a devastating and potentially life-threatening form of injury that can cause life-long chronic pain and other injury-associated symptoms and places an immense financial and social burden on the patients and their families
Consistent with previous studies, we found that neuron-glial antigen 2 (NG2) positive cells were detected in the marginal region of the lesion core in spinal cord injury (SCI) mice (Figure 1A), with NG2 expression found to be 10 times greater in mice with a demyelinating injury vs. control mice (Novotna et al, 2011; Hackett et al, 2016; Levine, 2016; Kucharova and Stallcup, 2017; Hesp et al, 2018)
Our previous study demonstrated that 1 week after SCI, the bone marrow-derived cells (BMDCs) around the lesion epicenter were BMDMφ since these BMDCs colocalized with key macrophage markers such as F4/80, CD68, and IBA-1, indicating that a vast majority of these cells were BMDMφ, rather than locally activated microglia (Wang et al, 2015)
Summary
Spinal cord injury (SCI) is a devastating and potentially life-threatening form of injury that can cause life-long chronic pain and other injury-associated symptoms and places an immense financial and social burden on the patients and their families. One key persistent characteristic of SCI that can occur as a result of the initial mechanical trauma, as well as develop as a progressive and chronic feature of secondary injury, is the demyelination of axons within and proximal to the injury site (Totoiu and Keirstead, 2005). It is this demyelination that leads to impaired axonal function and neuronal survival after injury (Almad et al, 2011).
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