Journal article
Neuroprotective effects of naltrexone in a mouse model of post-traumatic seizures
Scientific reports, Vol.14(1), 13507
06/12/2024
DOI: 10.1038/s41598-024-63942-8
PMCID: PMC11169394
PMID: 38867062
Abstract
Traumatic Brain Injury (TBI) induces neuroinflammatory response that can initiate epileptogenesis, which develops into epilepsy. Recently, we identified anti-convulsive effects of naltrexone, a mu-opioid receptor (MOR) antagonist, used to treat drug addiction. While blocking opioid receptors can reduce inflammation, it is unclear if post-TBI seizures can be prevented by blocking MORs. Here, we tested if naltrexone prevents neuroinflammation and/or seizures post-TBI. TBI was induced by a modified Marmarou Weight-Drop (WD) method on 4-week-old C57BL/6J male mice. Mice were placed in two groups: non-telemetry assessing the acute effects or in telemetry monitoring for interictal events and spontaneous seizures both following TBI and naltrexone. Molecular, histological and neuroimaging techniques were used to evaluate neuroinflammation, neurodegeneration and fiber track integrity at 8 days and 3 months post-TBI. Peripheral immune responses were assessed through serum chemokine/cytokine measurements. Our results show an increase in MOR expression, nitro-oxidative stress, mRNA expression of inflammatory cytokines, microgliosis, neurodegeneration, and white matter damage in the neocortex of TBI mice. Video-EEG revealed increased interictal events in TBI mice, with 71% mice developing post-traumatic seizures (PTS). Naltrexone treatment ameliorated neuroinflammation, neurodegeneration, reduced interictal events and prevented seizures in all TBI mice, which makes naltrexone a promising candidate against PTS, TBI-associated neuroinflammation and epileptogenesis in a WD model of TBI.
Details
- Title: Subtitle
- Neuroprotective effects of naltrexone in a mouse model of post-traumatic seizures
- Creators
- Saul Rodriguez - University of IowaShaunik Sharma - University of IowaGrant Tiarks - University of IowaZeru Peterson - University of IowaKyle Jackson - University of IowaDaniel Thedens - University of Iowa, Electrical and Computer EngineeringAngela Wong - University of Iowa, Stead Family Department of PediatricsDavid Keffala-Gerhard - University of IowaVinit B Mahajan - Stanford UniversityPolly J Ferguson - University of IowaElizabeth A Newell - University of IowaJoseph Glykys - University of IowaThomas Nickl-JockschatAlexander G Bassuk - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.14(1), 13507
- Publisher
- Nature Publishing Group
- DOI
- 10.1038/s41598-024-63942-8
- PMID
- 38867062
- PMCID
- PMC11169394
- eISSN
- 2045-2322
- Language
- English
- Date published
- 06/12/2024
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Radiology; Electrical and Computer Engineering; Psychiatry; Critical Care; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Rheumatology, Allergy, and Immunology; Neurology (Pediatrics)
- Record Identifier
- 9984642758802771
Metrics
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