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A Neuronal Apoptosis Model induced by Spinal Cord Compression in Rat
Published on: June 29, 2021
Anti-Apoptotic Effects of Dapsone After Spinal Cord Injury in Rats
Camilo Ríos1, Sandra Orozco-Suarez, Hermelinda Salgado-Ceballos
1Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez S.S.A., Ave. Insurgentes Sur No. 3877, 14269, Mexico City, DF, Mexico.
Abstract:
Spinal cord injury (SCI) is a condition producing irreversible damage to the neurological function. Among the leading mechanisms associated to cell death after SCI, excitotoxicity, oxidative stress, inflammatory response and apoptosis are considered potential targets to prevent tissue damage. We recently reported that dapsone an anti-inflammatory drug, decreases the activity of myeloperoxidase, lipid peroxidation, improve neurological function and increase the amount of spared tissue after SCI in rats. In this study, we characterized the anti-apoptotic effect of dapsone administered at 12.5 mg/kg/24 h dose, starting at 3 and 5 h after SCI. We monitored the activity of caspases-8, 9, and 3 and quantitated Annexin V and TUNEL positive cells in the core of the lesion. Results showed increased activities of caspase-8, 9 and 3 at 72 h by SCI to reach increments of 69, 143 and 293 %, respectively, as compared to sham group. Meanwhile, dapsone, administered at 3 and 5 after SCI, reduced caspase-8 activity by 36 and 44 % respectively, whereas the activity of caspase-9 was diminished by 37 %. Likewise, the activity of caspase-3 showed a decrease of 38 %. Finally, both Annexin V and TUNEL-positive cells were significantly reduced by DDS as compared to untreated SCI animals. Results showed that dapsone exerted anti-apoptotic effect after SCI.
Insights
Dapsone reduces cell death after spinal cord injury (SCI) by inhibiting apoptosis. This anti-inflammatory drug significantly decreased caspase activity and the number of apoptotic cells, promoting tissue survival post-SCI.
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- Spinal cord injury (SCI) causes irreversible neurological damage.
- Key mechanisms of cell death include excitotoxicity, oxidative stress, inflammation, and apoptosis.
- Dapsone, an anti-inflammatory drug, has previously shown neuroprotective effects in SCI models.
Purpose of the Study:
- To investigate the anti-apoptotic effects of dapsone in a rat model of SCI.
- To evaluate the impact of dapsone on caspase activity and apoptotic cell markers.
Main Methods:
- Dapsone (12.5 mg/kg/24 h) was administered 3 and 5 hours post-SCI.
- Caspase-8, -9, and -3 activities were measured at 72 hours.
- Annexin V and TUNEL staining quantified apoptotic cells in the lesion core.
Main Results:
- SCI significantly increased caspase-8, -9, and -3 activities (69-293%) compared to sham.
- Dapsone administration reduced caspase-8 (36-44%), caspase-9 (37%), and caspase-3 (38%) activities.
- Dapsone significantly decreased Annexin V and TUNEL-positive cells, indicating reduced apoptosis.
Conclusions:
- Dapsone exhibits significant anti-apoptotic effects following spinal cord injury.
- Early administration of dapsone mitigates key apoptotic pathways after SCI.
- These findings support dapsone as a potential therapeutic agent for SCI.

