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Activity-based Training on a Treadmill with Spinal Cord Injured Wistar Rats
Published on: January 16, 2019
Tibolone Improves Locomotor Function in a Rat Model of Spinal Cord Injury by Modulating Apoptosis and Autophagy
Stephanie Sánchez-Torres1,2, Carlos Orozco-Barrios3, Hermelinda Salgado-Ceballos1
1Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico.
Abstract:
Spinal cord injury (SCI) harms patients' health and social and economic well-being. Unfortunately, fully effective therapeutic strategies have yet to be developed to treat this disease, affecting millions worldwide. Apoptosis and autophagy are critical cell death signaling pathways after SCI that should be targeted for early therapeutic interventions to mitigate their adverse effects and promote functional recovery. Tibolone (TIB) is a selective tissue estrogen activity regulator (STEAR) with neuroprotective properties demonstrated in some experimental models. This study aimed to investigate the effect of TIB on apoptotic cell death and autophagy after SCI and verify whether TIB promotes motor function recovery. A moderate contusion SCI was produced at thoracic level 9 (T9) in male Sprague Dawley rats. Subsequently, animals received a daily dose of TIB orally and were sacrificed at 1, 3, 14 or 30 days post-injury. Tissue samples were collected for morphometric and immunofluorescence analysis to identify tissue damage and the percentage of neurons at the injury site. Autophagic (Beclin-1, LC3-I/LC3-II, p62) and apoptotic (Caspase 3) markers were also analyzed via Western blot. Finally, motor function was assessed using the BBB scale. TIB administration significantly increased the amount of preserved tissue (p < 0.05), improved the recovery of motor function (p < 0.001) and modulated the expression of autophagy markers in a time-dependent manner while consistently inhibiting apoptosis (p < 0.05). Therefore, TIB could be a therapeutic alternative for the recovery of motor function after SCI.
Insights
Tibolone (TIB) shows promise in treating spinal cord injury (SCI). This study found TIB preserved tissue, inhibited apoptosis, and improved motor function recovery in rats with SCI.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Pharmacology
Background:
- Spinal cord injury (SCI) presents significant health and socioeconomic challenges globally.
- Current therapeutic strategies for SCI remain limited, highlighting the need for novel treatments.
- Apoptosis and autophagy are key cellular processes influencing SCI outcomes and represent potential therapeutic targets.
Purpose of the Study:
- To investigate the neuroprotective effects of Tibolone (TIB) on apoptosis and autophagy following SCI.
- To determine if TIB administration promotes motor function recovery after SCI.
- To evaluate TIB's impact on cellular markers of cell death and survival post-injury.
Main Methods:
- A moderate contusion SCI model was established in Sprague Dawley rats.
- Rats received daily oral doses of TIB post-injury.
- Tissue analysis included morphometry, immunofluorescence, and Western blot for apoptosis and autophagy markers.
- Motor function was assessed using the BBB scale at various time points.
Main Results:
- TIB administration significantly increased preserved tissue volume (p < 0.05).
- TIB treatment consistently inhibited apoptosis (Caspase 3) and modulated autophagy markers (Beclin-1, LC3, p62) in a time-dependent manner (p < 0.05).
- Significant motor function recovery was observed in TIB-treated rats (p < 0.001).
Conclusions:
- Tibolone demonstrates significant neuroprotective effects in a rat SCI model.
- TIB effectively inhibits apoptosis and modulates autophagy, contributing to tissue preservation.
- TIB holds potential as a therapeutic agent for enhancing motor function recovery after spinal cord injury.
