Spinal cord injury in mice affects central and peripheral pathology in a severity-dependent manner

Abstract

Chronic pain is a common medical complication experienced by those living with spinal cord injury (SCI) and leads to worsened quality of life. The pathophysiology of SCI pain is poorly understood, hampering the development of safe and efficacious therapeutics. We therefore sought to develop a clinically relevant model of SCI with a strong pain phenotype and characterize the central and peripheral pathology after injury. A contusion (50 kdyn) injury, with and without sustained compression (60 seconds) of the spinal cord, was performed on female C57BL/6J mice. Mice with compression of the spinal cord exhibited significantly greater heat and mechanical hypersensitivity starting at 7 days postinjury, concomitant with reduced locomotor function, compared with those without compression. Immunohistochemical analysis of spinal cord tissue revealed significantly less myelin sparing and increased macrophage activation in mice with compression compared with those without. As measured by flow cytometry, immune cell infiltration and activation were significantly greater in the spinal cord (phagocytic myeloid cells and microglia) and dorsal root ganglia (Ly6C 1 monocytes) after compression injury. We also decided to investigate the gastrointestinal microbiome, as it has been shown to be altered in patients with SCI and has recently been shown to play a role in immune system maturation and pain. We found increased dysbiosis of the gastrointestinal microbiome in an injury severity-dependent manner. The use of this contusioncompression model of SCI may help advance the preclinical assessment of acute and chronic SCI pain and lead to a better understanding of mechanisms contributing to this pain.

Grafted human ESC-derived astroglia repair spinal cord injury via activation of host anti-inflammatory microglia in the lesion area

“…Pathologically, the blood-spinal-cord barrier (BSCB) is disruptured after spinal cord injury 49 , 50 , and leads to the infiltration of peripheral inflammatory cells and factors into the lesion area 51 . Recent studies have shown that peripheral macrophages affect the microenvironment of lesion area after SCI 52 - 54 , and crosstalk between peripheral macrophages and vessels endothelial cells in the lesion area after SCI is a potential therapy for SCI 55 . Moreover, ependymal cells can behave as multipotent spinal cord stem cells and form new neurons and glial cells 56 - 59 , which may affect the microenvironment of lesion area after SCI.…”

Mapping trends and hotspot regarding gastrointestinal microbiome and neuroscience: A bibliometric analysis of global research (2002–2022)

“…Brain-derived neurotrophic factors and Toll-like receptors were the key research factors ( Zeraati et al, 2019 ; Haghighat et al, 2021 ). Pathological experiments were the primary study methodology, while probiotic therapy was the primary research topic ( Akbari et al, 2016 ; Kozyrev et al, 2020 ; Bannerman et al, 2022 ; Pochakom et al, 2022 ). Notably, including “schizophrenia” (burst strength 4.35), “pathology” (burst strength 3.81), and “psychiatric disorder” (burst strength 3.26), which are the current research frontiers in this field and are currently within the burst period.…”