What is the Role of Immune Cells in the Pathophysiology Post Spinal Cord Injury?

Abstract

Introduction: Spinal cord injury triggers a host of immune responses that involve the release of Damage-associated molecular patterns (DAMPs), which in turn activate an inflammatory response. The inflammatory response following Spinal cord injuries (SCI) often becomes dysregulated and hyperactive, therefore giving way to secondary injury. This review focuses on the acute, ≤7 days, phase of SCI and discusses how various immune cells, including neutrophils, macrophages, microglia, and T cells, orchestrate SCI pathology. Elucidating these early-phase immune dynamics is very important because the degree of secondary tissue damage and the recovery outcome depend upon the nature of the initial immune response.

Methods: We synthesized primary studies dealing with immune cell behavior after SCI, focusing on neutrophils, macrophages, microglia, and T cells. Articles were identified from PubMed, MEDLINE, Embase, Cochrane, and McGill Library databases, considering studies in mouse models with experimental contusions or crush injuries. The articles were reviewed based on their investigation of immune infiltration and temporal immune responses.

Results: The acute immune response following SCI consists of rapid neutrophil infiltration within hours and a peak at 12-24 hours, which frequently correlates with the severity of the lesion. T-regulatory lymphocytes (Tregs) are recruited early on and help to modulate the inflammation, while microglia and macrophages follow and enter inflammatory states within one to three days. It was shown that while these cells promote injury, they also contribute to both injury and repair.

Conclusion: The early immune response after SCI is understudied. Gaining a more holistic understanding of it could allow us to develop immunotherapies which target and alter the inflammatory process during this critical window. Theoretically, medicines aimed at minimizing or preventing additional tissue damage and improving long-term recovery could be made possible by identifying the molecular drivers of early inflammation. According to the review, the acute period of SCI is an important topic for further exploration to guide treatments that aim to balance the early immune responses.