Expression and Localization of the Orexin-1 Receptor (OX1R) After Traumatic Brain Injury in Mice
Abstract
Orexins are neuropeptides that have a wide range of physiological effects, and recent studies have suggested that the orexin system may be involved in traumatic brain injury. However, the expression and localization of orexin receptors have not been examined yet under brain injury conditions. In the present study, we used immunohistochemical techniques to investigate the expression of orexin-1 receptor (OX1R) and its time-dependent changes in the mouse brain after controlled cortical impact (CCI) injury. OX1R-like immunoreactivity was first detected 6 h after injury in the surrounding penumbra of the injury. The intensity of this immunoreactivity was increased at 12 h, peaked at day 1, and then decreased from day 2 to day 7. To identify the cellular localization of OX1R, we also performed double-immunohistochemical staining with OX1R and several cell marker antibodies. OX1R-like immunopositive cells were clearly co-localized with immunoreactivity for the neuronal marker NeuN at day 7. It was also expressed on the periphery of cells immunopositive for CD11b, a microglial cell marker, at days 1 and 7. These results suggest that orexin and its receptor may play roles in traumatic brain injury, and that OX1R is induced in neurons and microglial cells after traumatic brain injury.
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Mihara et al. 2011 observed that orexin neuronal fibers were more present in the area surrounding the injury at 24 h and 7 days after injury as compared to uninjured animals.
“Mihara et al. 2011 observed that orexin neuronal fibers were more present in the area surrounding the injury at 24 h and 7 days after injury as compared to uninjured animals.89”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as Mihara et al. 2011
At 7 days after injury, orexin receptor expression was observed in microglia and neurons, but not in astrocytes.
“At 7 days after injury, orexin receptor expression was observed in microglia and neurons, but not in astrocytes.”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as Mihara et al. 2011
Mihara et al. 2011 found that orexin receptor expression at 24 h post-injury occurred in microglia only.
“In their study, orexin receptor expression at 24 h post-injury occurred in microglia only.”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as Mihara et al. 2011
Mihara et al. 2011 observed that orexin neuronal fibers were more present in the area surrounding the injury at 24 h and 7 days after injury as compared to uninjured animals.
“Mihara et al. 2011 observed that orexin neuronal fibers were more present in the area surrounding the injury at 24 h and 7 days after injury as compared to uninjured animals.89”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [89]
Several studies found an increase of orexin receptors compared to sham-injured animals after TBI.
“Several studies found an increase of orexin receptors compared to sham-injured animals after TBI,75–79,89”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [89]
Mihara et al. 2011 found that orexin receptor expression at 24 h post-injury occurred in microglia only.
“In their study, orexin receptor expression at 24 h post-injury occurred in microglia only.”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [89]
At 7 days after injury, orexin receptor expression was observed in microglia and neurons, but not in astrocytes.
“At 7 days after injury, orexin receptor expression was observed in microglia and neurons, but not in astrocytes.”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [89]
Another study reports that orexin receptors peak at 24 h post-injury and decrease after, though only qualitative findings are shown.
“Another study,89 also follows this trend and reports that orexin receptors peak at 24 h post-injury and decrease after, though this study only shows qualitative, not quantitative findings.”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [89]
Cites
A controlled cortical impact model of traumatic brain injury in the rat
Edward Dixon, C., Clifton, G. L., Lighthall, J. W., Yaghmai, A. A., & Hayes, R. L. (1991) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(91)90104-8 · Cited by 1,141 · see citing works
Sleep-wake disturbances 6 months after traumatic brain injury: a prospective study
Baumann, C. R., Werth, E., Stocker, R., Ludwig, S., & Bassetti, C. L. (2007) · Brain · doi:10.1093/brain/awm109 · Cited by 380 · see citing works
Loss of hypocretin (orexin) neurons with traumatic brain injury
Baumann, C. R., Bassetti, C. L., Valko, P. O., Haybaeck, J., Keller, M., Clark, E., Stocker, R., Tolnay, M., & Scammell, T. E. (2009) · Annals of Neurology · doi:10.1002/ana.21836 · Cited by 185 · see citing works
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Effects of Traumatic Brain Injury on the Orexin/Hypocretin System
Somach, R. T., Lim, M. M., & Cohen, A. S. (2025) · Neurotrauma Reports · doi:10.1089/neur.2024.0111 · Cited by 2 · see citing works
- Authors
- Mihara, Y., Dohi, K., Yofu, S., Nakamachi, T., Ohtaki, H., Shioda, S., & Aruga, T.
- Affiliations
- SHOWA Medical University (JP)
- Corresponding author
- Shioda, Seiji
- Venue
- Journal of Molecular Neuroscience
- Published
- 2010-08-28
- Volume
- 43
- Issue
- 2
- Pages
- 162-168
- ISSN
- 0895-8696 (ISSN-L)
- 1559-1166
- OpenAlex
- W2018345588
- Cited by
- 31
- References
- 3
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 2 · 2014: 4 · 2013: 2 · 2012: 1
- FWCI
- 0.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Molecular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (22791695)
- Topics
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Keywords
- orexin-1 receptor, orexin system, traumatic brain injury, controlled cortical impact, receptor expression, neuronal localization, microglia, CD11b, NeuN, time-course expression
- MeSH terms
- Orexins, Animals, Astrocytes, Brain Injuries, Male, Mice, Inbred C57BL, Neurons, Neuropeptides, Microglia, Receptors, Neuropeptide, Receptors, G-Protein-Coupled, Intracellular Signaling Peptides and Proteins, Mice, Orexin Receptors
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