Inflammation and spinal cord injury: Infiltrating leukocytes as determinants of injury and repair processes

Abstract

The immune response that accompanies spinal cord injury contributes to both injury and reparative processes. It is this duality that is the focus of this review. Here we consider the complex cellular and molecular immune responses that lead to the infiltration of leukocytes and glial activation, promote oxidative stress and tissue damage, influence wound healing, and subsequently modulate locomotor recovery. Immunomodulatory strategies to improve outcomes are gaining momentum as ongoing research carefully dissects those pathways, which likely mediate cell injury from those, which favor recovery processes. Current therapeutic strategies address divergent approaches including early immunoblockade and vaccination with immune cells to prevent early tissue damage and support a wound-healing environment that favors plasticity. Despite these advances, there remain basic questions regarding how inflammatory cells interact in the injured spinal cord. Such questions likely arise as a result of our limited understanding of immune cell/neural interactions in a dynamic environment that culminates in progressive cell injury, demyelination, and regenerative failure.

Effect of nimodipine on rat spinal cord injury

“…Research has shown that membrane damage is extensive and radicals, whose main role is to free or unsaturate fatty acid after the formation of lipid peroxide (LPO), therefore the content of LPO radical damage may reflect the degree of tissue cells (Trivedi et al, 2006;Lin et al, 2012;Chittiboina et al, 2012). SOD (superoxide dismutase) is the specificity of superoxide radical scavenging enzymes, it can significantly reduce free radical-mediated lipid peroxidation, lysosomal membrane stability, and thus the cell protective effect (Atılgan, 2012;Ouardouz et al, 2009;Hawryluk et al, 2008;Retraction, 2011;Paterniti et al, 2009;.…”

“…Blood flow changes after SCI, and extensive infiltration of inflammatory cells also result in a large amount of oxygen free radicals (Donnelly et al, 2008). After spinal cord injury, the major lipid peroxidation end product MDA and 4-Hydroxy Acrolein (4-HE) can be detected, indicating that lipid peroxidation is one of the pathological changes after spinal cord injury, experiments have proven to reduce lipid peroxidation after spinal cord injury to animals improving motor function (Trivedi et al, 2006;Paterniti et al, 2009;Retraction, 2011;Liu et al, 2011;Chittiboina et al, 2012). We also found that in the experiment, MDA levels in nimodipine group were significantly lower, indicating that nimodipine might play a role in anti-oxidation by scavenging free radicals.…”

The developing landscape of diagnostic and prognostic biomarkers for spinal cord injury in cerebrospinal fluid and blood

“…Infiltrating leukocytes and resident microglia release proteolytic and oxidative enzymes, 146 reactive oxygen species and an array of pro-inflammatory cytokines, including, for example, tumour 147 necrosis factor-alpha (TNF-α) (14,15). This spike in acute phase pro-inflammatory molecules can be 148 measured in human blood in the first 24h following injury (16).…”

Mesenchymal Stem Cell Therapy for Apoptosis After Spinal Cord Injury

“…In addition, grafted cells may provide a source of growth factors to enhance axonal elongation across spinal cord lesions (Wright et al, 2011). Moreover, SCI initiates an innate immune response that participates not only in secondary pathogenesis but also in wound healing (Trivedi et al, 2006). Even though the present data are promising, further research is needed to establish whether bone marrow cell treatments can serve as a safe and efficacious autologous source for the treatment of the injured SCI (Wright et al, 2011).…”