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Effects of Therapeutic Hypothermia on Apoptosis and Autophagy After Spinal Cord Injury in Rats
- Source :
- Spine. 40(12)
- Publication Year :
- 2015
-
Abstract
- Study design Animal study. Objective To further investigate the effects of therapeutic hypothermia (TH), the present study compared autophagy and apoptosis after treatment with either therapeutic moderate systemic hypothermia or methylprednisolone sodium succinate (MP) in a rat model of acute spinal cord injury (SCI). Summary of background data The neuroprotective effects of TH have recently become an important topic in the field of SCI research. Methods All rats were subjected to a 25-g/cm spinal cord contusion over the ninth thoracic vertebrae. After the induction of SCI, the control group did not receive any further treatment, TH group immediately received moderate systemic hypothermia for 4 hours, and MP group was administered high-dose MP. The rats were killed either 2 or 7 days after SCI, and the injured spinal cord tissues were obtained. Apoptosis and autophagy were assessed by immunohistochemical analyses and Western blot analyses. In addition, the microarchitecture of the autophagosomes was evaluated using transmission electron microscopy, and the motor activity of the rats was assessed using the Basso-Beattie-Bresnahan (BBB) locomotor rating scale. Results Compared with controls, there was a significant reduction in the expression levels of cleaved caspase-8, -9, and -3 in the TH- and MP-treated groups 2 days after SCI. Moreover, compared with the control group, the expression of LC3II and Beclin-1 exhibited a significant decrease on day 2 after treatment with TH. The numbers of transferase dUTP nicked-end labeling and LC3-positive cells were significantly lower on days 2 and 7. The Basso-Beattie-Bresnahan ratings were significantly higher 6 weeks after SCI in both the TH- and MP-treated groups than in the control group. Conclusion Both TH and MP have neuroprotective effects on injured spinal cord tissues via the inhibition of apoptosis and autophagy. Thus, the application of moderate systemic hypothermia may be a useful treatment modality after acute SCI. Level of evidence N/A.
- Subjects :
- Male
Time Factors
Blotting, Western
Apoptosis
Pharmacology
Motor Activity
Neuroprotection
Rats, Sprague-Dawley
Microscopy, Electron, Transmission
Hypothermia, Induced
medicine
Autophagy
Animals
Orthopedics and Sports Medicine
Methylprednisolone Hemisuccinate
Spinal cord injury
Spinal Cord Injuries
Behavior, Animal
business.industry
Hypothermia
medicine.disease
Spinal cord
Immunohistochemistry
Blot
Disease Models, Animal
medicine.anatomical_structure
Neuroprotective Agents
Spinal Cord
Cytoprotection
Anesthesia
Thoracic vertebrae
Neurology (clinical)
medicine.symptom
business
Apoptosis Regulatory Proteins
Subjects
Details
- ISSN :
- 15281159
- Volume :
- 40
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Spine
- Accession number :
- edsair.doi.dedup.....27ececb4c1befb74550bafb5df914177