Acute Spinal Cord Injury Induces Genetic Damage in Multiple Organs of Rats

Medalha, Carla Christina; Polesel, Fernanda Sato; Silva, Victor Hugo Pereira da; Martins, Renato A.; Pozzi, Renan; Ribeiro, Daniel Araki

doi:10.1007/s10571-012-9825-3

Cited by 6 publications

(5 citation statements)

References 21 publications

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“…Interestingly, Medalha et al . have demonstrated that acute DNA damage extends beyond the spinal cord in SCI rats to affect blood, liver, and the kidneys using the comet assay to detect DNA strand breaks (Medalha et al, 2012). …”

Section: Evidence For Dna Damage In Acute Cns Injuries and Neurodegenmentioning

confidence: 99%

Oxidative stress, DNA damage, and the telomeric complex as therapeutic targets in acute neurodegeneration

Smith¹,

Park²,

Krause³

et al. 2013

Neurochemistry International

148

100

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Oxidative stress has been identified as an important contributor to neurodegeneration associated with acute CNS injuries and diseases such as spinal cord injury (SCI), traumatic brain injury (TBI), and ischemic stroke. In this review, we briefly detail the damaging effects of oxidative stress (lipid peroxidation, protein oxidation, etc.) with a particular emphasis on DNA damage. Evidence for DNA damage in acute CNS injuries is presented along with its downstream effects on neuronal viability. In particular, unchecked oxidative DNA damage initiates a series of signaling events (e.g. activation of p53 and PARP-1, cell cycle re-activation) which have been shown to promote neuronal loss following CNS injury. These findings suggest that preventing DNA damage might be an effective way to promote neuronal survival and enhance neurological recovery in these conditions. Finally, we identify the telomere and telomere-associated proteins (e.g. telomerase) as novel therapeutic targets in the treatment of neurodegeneration due to their ability to modulate the neuronal response to both oxidative stress and DNA damage.

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Section: Evidence For Dna Damage In Acute Cns Injuries and Neurodegenmentioning

confidence: 99%

Oxidative stress, DNA damage, and the telomeric complex as therapeutic targets in acute neurodegeneration

Smith¹,

Park²,

Krause³

et al. 2013

Neurochemistry International

148

100

View full text Add to dashboard Cite

show abstract

“…Dagci et al 2009a found DNA strand breaks in the brain and kidney of SCI rats [ 53 ]. Consistently, Medalha et al showed DNA strand breaks in the liver and kidney [ 77 ], and Sakarcan et al similarly reported oxidative DNA damage (i.e., 8-oxodG) in the kidney [ 34 ]. The brain is directly connected to the spinal cord, and similar effects as in the spinal cord might be predicted.…”

Section: Oxidative Dna Damage Is Understudied After Scimentioning

confidence: 78%

“…Using HPLC, Ozgonul et al found DNA damage biomarkers (i.e., 5-(hydroxymethyl) uracil (5HMU) and 2′-deoxyuridine (2dU)) in the urine at sub-acute time points (7 dpi) and early chronic time points (28 dpi) [ 55 ]. In addition, Medalha et al showed DNA strand breaks using the comet assay in the blood of SCI rats at 1 dpi [ 77 ]. These findings indicate that factors produced at the injury site can traverse the disrupted blood–brain barrier and may have systemic effects.…”

Section: Oxidative Dna Damage Is Understudied After Scimentioning

confidence: 99%

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

2022

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Oxidative stress occurs at various phases of spinal cord injury (SCI), promoting detrimental processes such as free radical injury of proteins, nucleic acids, lipids, cytoskeleton, and organelles. Oxidative DNA damage is likely a major contributor to the pathogenesis of SCI, as a damaged genome cannot be simply turned over to avert detrimental molecular and cellular outcomes, most notably cell death. Surprisingly, the evidence to support this hypothesis is limited. There is some evidence that oxidative DNA damage is increased following SCI, mainly using comet assays and immunohistochemistry. However, there is great variability in the timing and magnitude of its appearance, likely due to differences in experimental models, measurement techniques, and the rigor of the approach. Evidence indicates that 8-oxodG is most abundant at 1 and 7 days post-injury (dpi), while DNA strand breaks peak at 7 and 28 dpi. The DNA damage response seems to be characterized by upregulation of PCNA and PARP1 but downregulation of APEX1. Significant improvements in the analysis of oxidative DNA damage and repair after SCI, including single-cell analysis at time points representative for each phase post-injury using new methodologies and better reporting, will uncover the role of DNA damage and repair in SCI.

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“…In the present study, the plasma nDNA level on day 14 was independently associated with outcome, suggesting that the therapeutic window is within the first 14 days after injury. Medalha et al [49] demonstrated that acute DNA damage extends beyond the spinal cord in SCI rats to affect the blood, liver, and kidneys. Bao et al [50] administrated a monoclonal antibody against CD11d integrin, an integral leukocyte adhesion protein that reduces oxidative stress-related DNA oxidation after severe compression injury.…”

Section: Discussionmentioning

confidence: 99%

Serial plasma DNA levels as predictors of outcome in patients with acute traumatic cervical spinal cord injury

et al. 2019

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Background Acute traumatic cervical spinal cord injury (SCI) is a leading cause of disability in adolescents and young adults worldwide. Evidence from previous studies suggests that circulating cell-free DNA is associated with severity following acute injury. The present study determined whether plasma DNA levels in acute cervical SCI are predictive of outcome. Methods In present study, serial plasma nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) levels were obtained from 44 patients with acute traumatic cervical SCI at five time points from day 1 to day 180 post-injury. Control blood samples were obtained from 66 volunteers. Results Data showed a significant increase in plasma nDNA and mtDNA concentrations at admission in SCI patients compared to the control group. Plasma nDNA levels at admission, but not plasma mtDNA levels, were significantly associated with the Japanese Orthopaedic Association (JOA) score and Injury Severity Score in patients with acute traumatic cervical SCI. In patients with non-excellent outcomes, plasma nDNA increased significantly at days 1, 14 and 30 post-injury. Furthermore, its level at day 14 was independently associated with outcome. Higher plasma nDNA levels at the chosen cutoff point (> 45.6 ng/ml) predicted poorer outcome with a sensitivity of 78.9% and a specificity of 78.4%. Conclusions These results indicate JOA score performance and plasma nDNA levels reflect the severity of spinal cord injury. Therefore, the plasma nDNA assays can be considered as potential neuropathological markers in patients with acute traumatic cervical SCI.

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Acute Spinal Cord Injury Induces Genetic Damage in Multiple Organs of Rats

Cited by 6 publications

References 21 publications

Oxidative stress, DNA damage, and the telomeric complex as therapeutic targets in acute neurodegeneration

Oxidative stress, DNA damage, and the telomeric complex as therapeutic targets in acute neurodegeneration

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

Serial plasma DNA levels as predictors of outcome in patients with acute traumatic cervical spinal cord injury

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