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Updated: Jun 12, 2025
Controlled Cortical Impact Model for Traumatic Brain Injury
Published on: August 5, 2014
Neuroprotection unveiled: melatonin mitigates apoptotic pathways in traumatic brain injury
Sezer Onur Gunara1,2, Mehmet Yigit Akgun1,2, Ugur Seker3
1Department of Neurosurgery, Koc University Hospital, Istanbul, Türkiye.
Objective:
This study investigated the neuroprotective effects of melatonin in mice subjected to traumatic brain injury (TBI), focusing on caspase-dependent apoptotic signaling pathways.
Materials And Methods:
A total of 21 mice were divided into three groups: control, trauma (TBI), and trauma + melatonin (TBI + M). TBI was induced in the TBI and TBI + M groups via a free-fall impact on the frontal lobes. A single dose of 10 mg/kg of melatonin was intraperitoneally administered to the TBI + M group. Brain tissues were collected for histological evaluation and immunohistochemical analysis of apoptotic proteins.
Results:
The control group showed normal brain morphology, while the trauma group exhibited significant tissue loss and demyelination. The TBI + M group demonstrated reduced demyelination compared to the trauma group. An immunohistochemical analysis revealed increased expression of Bax and decreased expression of Bcl-2 in the trauma group, both of which were mitigated by melatonin treatment. The expression levels of caspase-3 and caspase-9 were elevated in the trauma group, whereas the TBI + M group showed expression levels comparable to the control group.
Conclusion:
TBI increased apoptotic protein expression, indicating neurodegeneration. The administration of melatonin at 10 mg/kg attenuated TBI-induced apoptosis and demyelination while promoting anti-apoptotic protein expression in the experimental model. These findings suggest a potential therapeutic role for melatonin in the management of TBI.
Insights
Melatonin treatment reduced brain damage and demyelination after traumatic brain injury (TBI) in mice. It also decreased apoptosis by modulating key proteins, suggesting a therapeutic role for melatonin in TBI management.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Traumatic brain injury (TBI) is a significant cause of mortality and disability.
- Apoptosis plays a critical role in TBI-induced neurodegeneration.
- Current TBI treatments are limited, necessitating the exploration of novel therapeutic agents.
Purpose of the Study:
- To investigate the neuroprotective effects of melatonin in a mouse model of TBI.
- To elucidate the role of melatonin in modulating caspase-dependent apoptotic pathways following TBI.
Main Methods:
- TBI was induced in mice using a free-fall impact model.
- Mice were divided into control, TBI, and TBI + melatonin groups.
- Histological and immunohistochemical analyses were performed to assess brain damage and apoptotic protein expression.
Main Results:
- TBI caused significant brain tissue loss, demyelination, and increased expression of pro-apoptotic proteins (Bax, caspase-3, caspase-9).
- Melatonin treatment (10 mg/kg) attenuated demyelination and reduced the expression of pro-apoptotic proteins.
- Melatonin administration also led to increased expression of anti-apoptotic protein Bcl-2.
Conclusions:
- Melatonin exhibits significant neuroprotective effects against TBI in mice.
- Melatonin attenuates TBI-induced apoptosis and demyelination by modulating apoptotic signaling pathways.
- Melatonin holds promise as a potential therapeutic agent for managing TBI.
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