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Updated: Oct 15, 2025
Electromagnetic Controlled Closed-Head Model of Mild Traumatic Brain Injury in Mice
Published on: September 28, 2022
Deficiency in Androgen Receptor Aggravates Traumatic Brain Injury-Induced Pathophysiology and Motor Deficits in Mice
Yu-Hsin Chen1, Yen-Chou Chen1, Ling-Ling Hwang1
1Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
Abstract:
Androgens have been shown to have a beneficial effect on brain injury and lower reactive astrocyte expression after TBI. Androgen receptors (ARs) are known to mediate the neuroprotective effects of androgens. However, whether ARs play a crucial role in TBI remains unknown. In this study, we investigated the role of ARs in TBI pathophysiology, using AR knockout (ARKO) mice. We used the controlled cortical impact model to produce primary and mechanical brain injuries and assessed motor function and brain-lesion volume. In addition, the AR knockout effects on necrosis and autophagy were evaluated after TBI. AR knockout significantly increased TBI-induced expression of the necrosis marker alpha-II-spectrin breakdown product 150 and astrogliosis marker glial fibrillary acidic protein. In addition, the TBI-induced astrogliosis increase in ARKO mice lasted for three weeks after a TBI. The autophagy marker Beclin-1 was also enhanced in ARKO mice compared with wild-type mice after TBI. Our results also indicated that ARKO mice showed a more unsatisfactory performance than wild-type mice in a motor function test following TBI. Further, they were observed to have more severe lesions than wild-type mice after injury. These findings strongly suggest that ARs play a role in TBI.
Insights
Androgen receptors (ARs) are crucial for mitigating brain injury after TBI. AR knockout mice showed worsened outcomes, indicating ARs protect against TBI-related damage.
Area of Science:
- Neuroscience
- Traumatic Brain Injury Research
- Molecular Biology
Background:
- Androgens show neuroprotective effects post-brain injury, mediated by androgen receptors (ARs).
- The specific role of ARs in traumatic brain injury (TBI) pathophysiology remains unclear.
- Investigating ARs is vital for understanding TBI mechanisms and potential therapeutic targets.
Purpose of the Study:
- To elucidate the role of androgen receptors (ARs) in the pathophysiology of traumatic brain injury (TBI).
- To assess the impact of AR deficiency on neurological function and brain lesion development after TBI.
- To evaluate the effects of AR knockout on cellular processes like necrosis and autophagy post-TBI.
Main Methods:
- Utilized a controlled cortical impact model to induce TBI in AR knockout (ARKO) and wild-type mice.
- Assessed motor function and quantified brain-lesion volume following TBI.
- Evaluated markers of necrosis (alpha-II-spectrin breakdown product 150), astrogliosis (glial fibrillary acidic protein), and autophagy (Beclin-1) post-injury.
Main Results:
- AR knockout significantly exacerbated TBI-induced expression of necrosis and astrogliosis markers.
- Increased astrogliosis in ARKO mice persisted for three weeks post-TBI.
- ARKO mice exhibited impaired motor function and larger brain lesions compared to wild-type controls.
- Autophagy marker Beclin-1 was elevated in ARKO mice after TBI.
Conclusions:
- Androgen receptors play a significant protective role in the context of traumatic brain injury.
- AR deficiency leads to increased neuronal damage, inflammation, and functional deficits after TBI.
- These findings highlight ARs as potential therapeutic targets for managing TBI.
