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Published on: July 11, 2017
Delayed administration of dapsone protects from tissue damage and improves recovery after spinal cord injury
Araceli Diaz-Ruiz1, Hermelinda Salgado-Ceballos, Sergio Montes
1Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez S.S.A., México D.F., México.
Abstract:
After spinal cord injury (SCI), a complex cascade of pathophysiological processes increases the primary damage. The inflammatory response plays a key role in this pathology. Recent evidence suggests that myeloperoxidase (MPO), an enzyme produced and released by neutrophils, is of special importance in spreading tissue damage. Dapsone (4,4'-diaminodiphenylsulfone) is an irreversible inhibitor of MPO. Recently, we demonstrated, in a model of brain ischemia/reperfusion, that dapsone has antioxidant, antiinflammatory, and antiapoptotic effects. The effects of dapsone on MPO activity, lipid peroxidation (LP) processes, motor function recovery, and the amount of spared tissue were evaluated in a rat model of SCI. MPO activity had increased 24.5-fold 24 hr after SCI vs. the sham group, and it had diminished by 38% and 19% in the groups treated with dapsone at 3 and 5 hr after SCI, respectively. SCI increased LP by 45%, and this increase was blocked by dapsone. In rats treated with dapsone, a significant motor function recovery (Basso-Beattie-Bresnahan score, BBB) was observed beginning during the first week of evaluation and continuing until the end of the study. Spontaneous recovery 8 weeks after SCI was 9.2 ± 1.12, whereas, in the dapsone-treated groups, it reached 13.6 ± 1.04 and 12.9 ± 1.17. Spared tissue increased by 42% and 33% in the dapsone-treated groups (3 and 5 hr after SCI, respectively) vs. SCI without treatment. Dapsone significantly prevented mortality. The results show that inhibition of MPO by dapsone significantly protected the spinal cord from tissue damage and enhanced motor recovery after SCI.
Insights
Dapsone, an inhibitor of myeloperoxidase (MPO), significantly reduced spinal cord damage and improved motor function recovery in rats after spinal cord injury (SCI). This neuroprotective effect highlights dapsone
Area of Science:
- Neuroscience
- Pharmacology
- Inflammation Research
Background:
- Spinal cord injury (SCI) triggers complex pathophysiological processes, including inflammation, that exacerbate primary damage.
- Myeloperoxidase (MPO), an enzyme released by neutrophils, plays a critical role in secondary tissue damage following SCI.
- Dapsone is an established MPO inhibitor with demonstrated antioxidant, anti-inflammatory, and antiapoptotic effects in other models.
Purpose of the Study:
- To evaluate the efficacy of dapsone in mitigating MPO activity, lipid peroxidation, and tissue damage after SCI in a rat model.
- To assess the impact of dapsone treatment on motor function recovery and the amount of spared spinal cord tissue post-SCI.
Main Methods:
- Rats with SCI were treated with dapsone at 3 and 5 hours post-injury.
- Measurements included MPO activity, lipid peroxidation (LP) levels, motor function (Basso-Beattie-Bresnahan score), and histological assessment of spared tissue.
- Mortality rates were also monitored.
Main Results:
- Dapsone treatment significantly reduced elevated MPO activity (by 38% and 19% at 3 and 5 hr post-SCI, respectively) and blocked SCI-induced lipid peroxidation.
- Dapsone administration led to significant motor function recovery (BBS scores improved from 9.2 to 13.6/12.9) and increased spared spinal cord tissue (by 42% and 33%).
- Dapsone treatment also significantly reduced mortality following SCI.
Conclusions:
- Inhibition of MPO by dapsone provides significant neuroprotection against secondary damage after SCI.
- Dapsone treatment enhances motor function recovery and preserves spinal cord tissue, suggesting therapeutic potential for SCI management.
- Early intervention with dapsone may be crucial for maximizing functional recovery and reducing mortality after spinal cord injury.
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