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Updated: Jun 9, 2026

Controlled Cortical Impact Model for Traumatic Brain Injury
Published on: August 5, 2014
Expression and localization of the orexin-1 receptor (OX1R) after traumatic brain injury in mice
Yuko Mihara1, Kenji Dohi, Sachiko Yofu
1Department of Emergency and Critical Care Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
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.
Insights
Orexin-1 receptors (OX1R) are found in neurons and microglial cells after traumatic brain injury. This suggests orexins play a role in brain injury recovery and response.
Area of Science:
- Neuroscience
- Neuroinflammation
- Traumatic Brain Injury
Background:
- Orexins are neuropeptides with diverse physiological roles.
- Emerging evidence suggests orexin system involvement in traumatic brain injury (TBI).
- Orexin receptor expression and localization post-TBI remain uncharacterized.
Purpose of the Study:
- To investigate the expression and localization of orexin-1 receptor (OX1R) in the mouse brain following controlled cortical impact (CCI) injury.
- To determine the time-dependent changes in OX1R expression after TBI.
- To identify the specific cell types expressing OX1R post-TBI.
Main Methods:
- Immunohistochemistry was used to detect OX1R expression.
- Controlled cortical impact (CCI) model was employed in mice.
- Double-immunohistochemical staining with neuronal (NeuN) and microglial (CD11b) markers was performed.
Main Results:
- OX1R immunoreactivity was detected 6 hours post-injury, peaking at day 1 and decreasing by day 7.
- OX1R was co-localized with the neuronal marker NeuN at day 7.
- OX1R was expressed on microglial cells (CD11b+) at days 1 and 7 post-injury.
Conclusions:
- Orexin-1 receptors are dynamically expressed in the brain after TBI.
- OX1R is induced in both neurons and microglial cells following traumatic brain injury.
- These findings suggest a potential role for the orexin system in TBI pathophysiology and recovery.

