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  4. Acute and non-resolving inflammation associate with oxidative injury after human spinal cord injury

Acute and non-resolving inflammation associate with oxidative injury after human spinal cord injury

Brain, 2021 · DOI: 10.1093/brain/awaa360 · Published: December 1, 2020

Spinal Cord InjuryNeurologyGenetics

Simple Explanation

This study examines the inflammatory response and tissue damage in human spinal cord injuries. It compares spinal cord tissue from individuals with traumatic injuries to those without, focusing on immune cells and oxidative damage. The research identifies different patterns of inflammation in the core of the injury versus the surrounding tissue. The lesion core showed infiltration of blood-derived macrophages, while the surrounding rim showed proliferation of microglia with a pro-inflammatory phenotype. The study also found evidence of long-term oxidative damage in the tissue surrounding the injury, suggesting it may contribute to ongoing problems after the initial trauma.

Study Duration
1.5 years
Participants
22 traumatic SCI patients and five non-traumatic control patients
Evidence Level
Not specified

Key Findings

  • 1
    Microglia were rapidly lost in the lesion core, while blood-borne macrophages dominated, showing an intermediate activation phenotype.
  • 2
    TMEM119 + microglia numbers were maintained through local proliferation in the surrounding rim and demonstrated a predominantly pro-inflammatory phenotype.
  • 3
    Oxidative neuronal injury remained significantly elevated up to months/years within the surrounding rim, indicating ongoing neuronal damage.

Research Summary

This study provides a detailed characterization of inflammatory responses and oxidative tissue injury in human traumatic spinal cord injury (SCI) lesions compared to non-traumatic control cords. The study identified distinct inflammatory patterns within the lesion core and the surrounding rim, with different types of immune cells and activation states dominating each area. The research found evidence of long-lasting oxidative damage in the lesion rim, suggesting its contribution to protracted injury and neurodegeneration after SCI.

Practical Implications

Targeted Therapies

The different inflammatory cellular composition and activation in the lesion core compared with its rim results in distinct inflammatory milieus of relevance for topical cell transplantation, but also neuroprotective, or immunomodulatory interventions in SCI patients.

Rehabilitation Strategies

Long-lasting oxidative tissue injury might be a substantial contributor to (i) an impaired response to rehabilitation; (ii) overall failure of recovery; or (iii) delayed loss of recovered function. This suggests the need for therapies addressing oxidative stress to improve rehabilitation outcomes.

Personalized Medicine

The identification of a subpopulation of SCI patients with B cell infiltration and antibody synthesis suggests that B cell- and antibody-mediated neurotoxic immune mechanisms may contribute to tissue injury in a subset of SCI patients. These patients may benefit from targeted immunotherapies.

Study Limitations

  • 1
    Lack of data on methylprednisolone treatment in the acute phase of injury
  • 2
    Inability to determine the influence of SCI severity on inflammation within the lesions
  • 3
    Challenges in detecting interleukins via immunohistochemistry in archival tissue

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