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An Ex Vivo Laser-induced Spinal Cord Injury Model to Assess Mechanisms of Axonal Degeneration in Real-time
Published on: November 25, 2014
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Chronic oxycodone induces axonal degeneration in rat brain.
Ruping Fan1, Lisa M Schrott2, Thomas Arnold1
1Department of Emergency Medicine, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, USA.
BMC Neuroscience
|March 25, 2018
Summary
Chronic opioid use can cause brain damage, including demyelination and axonal injury. This study reveals that opioids activate the integrated stress response, leading to neuronal apoptosis and white matter damage.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- Opioid therapy for non-malignant pain has risen, raising concerns about neurotoxicity.
- Long-term opioid use is linked to brain structure changes like leukoencephalopathy and white matter lesions.
- Mechanisms of opioid neurotoxicity on the central nervous system (CNS) require further elucidation.
Purpose of the Study:
- To investigate the neurotoxic effects of chronic opioid administration.
- To explore the role of the integrated stress response (ISR) in opioid-induced neurodegeneration.
- To examine opioid-induced demyelination and axonal damage in an animal model and cell cultures.
Main Methods:
- Female rats were administered oxycodone (15 mg/kg) orally for 30 days.
- Oxycodone, morphine, and DAMGO effects were tested on MCF7 cells expressing μ-opioid receptors.
- Biomarkers for axonal damage, myelin integrity, apoptosis, and ISR were analyzed.
Main Results:
- Oxycodone treatment caused axonal track deformation, reduced fascicle size, myelin loss, and β-APP accumulation in rats.
- Opioid exposure activated pro-apoptotic pathways and the ISR in rat white matter and MCF7 cells.
- The ISR inhibitor ISRIB reduced opioid-induced Bax and CHOP expression in MCF7 cells.
Conclusions:
- Chronic opioid administration may induce neuronal degeneration via ISR activation and subsequent apoptotic signaling.
- Opioid use can promote demyelination in the CNS.
- These findings highlight potential neurotoxic mechanisms of long-term opioid therapy.
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