The pathophysiological role of acute inflammation after spinal cord injury

Inflammation and Regeneration, 2016 · DOI: 10.1186/s41232-016-0026-1 · Published: August 10, 2016

Simple Explanation

Traumatic spinal cord injury (SCI) causes irreparable severe motor and sensory dysfunction. Mechanical trauma rapidly leads to blood-spinal cord barrier disruption, neural cell death, axonal damage, and demyelination, followed by a cascade of secondary injury that expands the additional inflammatory reaction at the lesion site. Although the role of inflammation in this phase is complex, a number of studies have suggested that inflammatory responses spread the damage to the surrounding tissue, induce apoptotic cell death, and impair spontaneous regeneration and functional recovery. A better understanding of the pathophysiological role of inflammation in the acute phase of SCI will aid in the development of therapeutic strategy to enhance the functional recovery after SCI.

Study Duration

Not specified

Participants

Mouse SCI model, 528 human SCI subjects

Evidence Level

Not specified

Key Findings

1
BLT1-knockout mice exhibited a 23 % decrease in neutrophils and 10 % decrease in macrophages after SCI compared to the wild-type mice.
2
Hyperglycemia induced the overactivation of NF-kB in microglial cells as well as excessive inflammation, resulting in a poor functional recovery after SCI.
3
The infiltrating Ly6C+Ly6G−fraction showed proinflammatory properties with elevated expression of IL-1β and TNFα. In contrast, we confirmed that the Ly6C+Ly6G−fraction had elevated expression of both iNOS and arginase 1.

Research Summary

Traumatic SCI leads to secondary injury via inflammation, which can spread damage, induce cell death and impair recovery. However, inflammation also has beneficial aspects like neuroprotection and debris removal. IL-6 signaling has context-dependent actions in SCI. It acts primarily as a proinflammatory mediator and causes secondary injury during the acute phase but enhances the repair process after the sub-acute phase of SCI. Infiltrating Ly6C+Ly6G−immature monocyte fraction exhibited the same characteristics as myeloid-derived suppressor cells (MDSCs) and played a critical role in the resolution of acute inflammation and in the subsequent tissue repair after SCI

Practical Implications

Therapeutic Target: LTB4-BLT1 Pathway

Neutralizing LTB4 has potential as a therapeutic strategy during the acute phase of SCI due to its role in amplifying neutrophils and macrophages infiltration.

Clinical Implication: Glycemic Control

Achieving tight glycemic control in acute human SCI is important to obtain better neurological outcomes by preventing hyperglycemia-related overactivation of NF-kB in microglia.

Therapeutic Potential: MDSC Transplantation

MDSC-based therapeutic strategy for the acute phase of SCI is suggested by the clarified role of MDSCs after traumatic SCI, indicating their potential utility.

Study Limitations

1
The mechanism underlying this inflammatory resolution is largely unknown.
2
Whether or not neuroinflammation after SCI has a neurotoxic or neuroprotective effect remains highly controversial.
3
Only minor attention has been paid to the role of inflammation in tissue protection after SCI thus far

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