Oxidative DNA Damage in the Pathophysiology of Spinal Cord Injury: Seems Obvious, but Where Is the Evidence?

Elle E M Scheijen1, Sven Hendrix2, David M Wilson1

  • 1Neurosciences, Biomedical Research Institute, Hasselt University, Agoralaan Building C, 3590 Diepenbeek, Belgium.

Insights

Oxidative DNA damage is a key factor in spinal cord injury (SCI) pathogenesis, but research is limited. Improved analysis methods are needed to understand DNA damage and repair roles in SCI recovery.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Spinal cord injury (SCI) involves oxidative stress, damaging cellular components like DNA.
  • Oxidative DNA damage is hypothesized to significantly contribute to SCI pathogenesis and cell death.
  • Current evidence linking oxidative DNA damage to SCI is limited and shows high variability.

Purpose of the Study:

  • To review the current evidence on oxidative DNA damage following SCI.
  • To highlight the need for improved methodologies in analyzing DNA damage and repair in SCI.
  • To underscore the potential role of DNA damage and repair in SCI pathogenesis and outcomes.

Main Methods:

  • Review of existing literature on oxidative DNA damage in SCI.
  • Analysis of studies using comet assays and immunohistochemistry to detect DNA damage.
  • Examination of DNA damage response markers such as 8-oxodG, DNA strand breaks, PCNA, PARP1, and APEX1.

Main Results:

  • Oxidative DNA damage is increased after SCI, but timing and magnitude vary.
  • Specific markers like 8-oxodG peak at 1-7 days post-injury (dpi), while DNA strand breaks peak at 7-28 dpi.
  • The DNA damage response involves upregulation of PCNA and PARP1, and downregulation of APEX1.

Conclusions:

  • Oxidative DNA damage is a significant factor in SCI, contributing to cell death.
  • Variability in findings necessitates standardized and advanced analytical techniques.
  • Further research using improved methodologies, including single-cell analysis, is crucial to elucidate the role of DNA damage and repair in SCI.

Related Concept Videos

Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Neurogenesis and Regeneration of Nervous Tissue01:15

Neurogenesis and Regeneration of Nervous Tissue

In the CNS, neurogenesis, the birth of new neurons from stem cells, is limited to the hippocampus in adults. In other regions of the brain and spinal cord, neurogenesis is almost non-existent due to inhibitory influences from neuroglia, especially oligodendrocytes, and the absence of growth-stimulating cues. The myelin produced by oligodendrocytes in the CNS inhibits neuronal regeneration. Furthermore, astrocytes proliferate rapidly after neuronal damage, forming scar tissue that physically...
Cellular Injury I: Introduction01:00

Cellular Injury I: Introduction

Cellular injury occurs when a cell cannot maintain homeostasis or adapt to stressors such as hypoxia, toxins, or trauma. Depending on severity and duration, injury may be reversible, allowing recovery, or irreversible, leading to cell death.General Mechanisms of Cell InjuryAlthough causes vary, most cellular injuries arise from a few key mechanisms that disrupt essential functions and often amplify one another. Cell survival depends on the extent and balance of these disturbances.ATP depletion...
Spinal Cord Injury ll: Pathophysiology01:14

Spinal Cord Injury ll: Pathophysiology

Spinal cord injury progresses through two interconnected phases: primary injury and secondary injury.Primary InjuryPrimary injury happens at the moment of trauma and involves immediate mechanical damage to the spinal cord.Compression happens when broken vertebrae, herniated discs, or accumulating blood (such as a hematoma) press directly against the spinal cord, distorting its normal shape and function. In cases of contusion, the cord is bruised by a blunt force (like penetrating injuries or...
Secondary Spinal Cord Injury llI: Pathophysiology01:25

Secondary Spinal Cord Injury llI: Pathophysiology

Early Ischemia and Ionic ImbalanceWithin minutes of spinal cord injury, a secondary cascade begins, progressing over hours to weeks. Vascular damage reduces blood flow, causing ischemia and mitochondrial dysfunction. ATP depletion leads to ion pump failure, membrane depolarization, sodium influx, potassium efflux, and water accumulation, resulting in cellular swelling. Increased intracellular calcium further disrupts mitochondria and accelerates cellular injury.Excitotoxicity and Neuronal...