Role of phospholipase A2s and lipid mediators in secondary damage after spinal cord injury

Abstract

Inflammation is considered to be an important contributor to secondary damage after spinal cord injury (SCI). This secondary damage leads to further exacerbation of tissue loss and functional impairments. The immune responses that are triggered by injury are complex and are mediated by a variety of factors that have both detrimental and beneficial effects. In this review, we focus on the diverse effects of the phospholipase A(2) (PLA(2)) superfamily and the downstream pathways that generate a large number of bioactive lipid mediators, some of which have pro-inflammatory and demyelinating effects, whereas others have anti-inflammatory and pro-resolution properties. For each of these lipid mediators, we provide an overview followed by a discussion of their expression and role in SCI. Where appropriate, we have compared the latter with their role in other neurological conditions. The PLA(2) pathway provides a number of targets for therapeutic intervention for the treatment of SCI and other neurological conditions.

Neuroinflammation: the devil is in the details

“…Another example of traumatic CNS injury is spinal cord injury (SCI). SCI is characterized both by the acute and focal contusion, as well as by an extensive secondary injury composed of ischemia, excitotoxicity, and inflammation (David et al 2012). The initial, acute period of inflammation is characterized by an influx of neutrophils and monocytes into the damaged region of the spinal cord (Pineau et al 2010).…”

Maresin 1 Promotes Inflammatory Resolution, Neuroprotection, and Functional Neurological Recovery After Spinal Cord Injury

“…Spinal cord injury (SCI) causes an immune response (David et al, 2012a;Gomez-Nicola and Perry, 2015;Steinman, 2015) composed of activated resident glial cells (microglia and astrocytes) and blood-derived leukocytes (neutrophils, monocytes, and lymphocytes) that enter the damaged spinal cord (Hawthorne and Popovich, 2011;Prüss et al, 2011;David et al, 2012a). These immune cells are required for effective clearance of damaged cell and myelin debris and for the release of bioactive molecules that lead to tissue healing and repair (Popovich and Longbrake, 2008;David et al, 2012a). However, they also secrete several factors that mediate cytotoxicity to neurons, glia, axons, and myelin (Popovich and Longbrake, 2008;David et al, 2012a).…”

“…These immune cells are required for effective clearance of damaged cell and myelin debris and for the release of bioactive molecules that lead to tissue healing and repair (Popovich and Longbrake, 2008;David et al, 2012a). However, they also secrete several factors that mediate cytotoxicity to neurons, glia, axons, and myelin (Popovich and Longbrake, 2008;David et al, 2012a). Therefore, the inflammatory response exerts both helpful and detrimental actions after SCI, so its final outcome on this pathology depends on the balance between mechanisms that regulate different aspects of the inflammatory response.…”

Beneficial effects of IL-37 after spinal cord injury in mice

“…After spinal cord contusion or compression injury, there is a rapid initiation of inflammation in rodents and in humans (2). This response is orchestrated by endogenous microglial cells and by circulating leukocytes, especially monocytes and neutrophils, which invade the lesion site during the first hours and days after injury (2)(3)(4). Although these cells are required for the clearance of cellular and myelin debris, they also release cytokines and cytotoxic factors, which are harmful to neurons, glia, axons, and myelin, resulting in secondary damage to adjacent regions of the spinal cord that had been previously unaffected by the insult (2,5,6).…”