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Updated: Sep 12, 2025
A Novel Model of Mild Traumatic Brain Injury for Juvenile Rats
Published on: December 8, 2014
Protective Effects of MK-801 on Apoptosis in Immature Rats With Traumatic Brain Injury
Ayşe Çiğel1, Oya Sayın2, Seren Gülşen Gürgen3
1Department of Physiology, Izmir Democracy University Faculty of Medicine, Izmir, Turkey.
Insights
MK-801, an NMDA receptor antagonist, reduces apoptosis in the hippocampus following traumatic brain injury (TBI) in young rats. This neuroprotective effect is achieved by downregulating key apoptotic markers, suggesting therapeutic potential for TBI.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Traumatic brain injury (TBI) is a significant cause of childhood morbidity and mortality.
- Understanding the mechanisms of TBI-induced neuronal damage is crucial for developing effective treatments.
Purpose of the Study:
- To evaluate the neuroprotective effects of MK-801, a noncompetitive NMDA receptor antagonist, on hippocampal damage in young rats following TBI.
- To assess the impact of MK-801 on apoptotic markers in the hippocampus after contusion injury.
Main Methods:
- Wistar Albino rats were divided into control, TBI, and MK-801 treatment groups.
- MK-801 (1 mg/kg) was administered intraperitoneally immediately after TBI induction.
- Apoptotic damage was assessed by measuring immunoreactivity for BAX, cytochrome c, and caspase-3 in the hippocampus.
Main Results:
- TBI significantly increased BAX and cytochrome c immunoreactivity in the hippocampus compared to controls.
- MK-801 treatment markedly reduced BAX and cytochrome c immunoreactivity in TBI rats.
- Caspase-3 immunoreactivity was intense in TBI rats but significantly reduced in the MK-801 group.
Conclusions:
- MK-801 significantly reduces hippocampal apoptosis following TBI in young rats.
- The drug downregulates key pro-apoptotic markers: BAX, cytochrome c, and caspase-3.
- MK-801 demonstrates neuroprotective potential by interfering with the intrinsic apoptotic pathway after TBI.
Introduction:
Traumatic brain injury (TBI) is a major public health problem and an essential cause of morbidity and mortality during childhood. The aim of this study was to evaluate the apoptotic effects of MK-801, a noncompetitive NMDA receptor antagonist, on hippocampal damage in 10-day-old rat pups exposed to contusion injury.
Methods:
Forty-two Wistar Albino rats were randomly assigned to three groups (n = 14 per group): control, trauma and MK-801 treatment. In the treatment group, MK-801 was administered intraperitoneally at a dose of 1 mg/kg immediately after induction of TBI. Apoptotic damage in the hippocampal dentate gyrus (DG) and CA1 regions was assessed using immunoreactivity for BAX, cytochrome c and caspase-3.
Results:
The control group showed low levels of BAX and cytochrome c immunoreactivity in the hippocampus, whereas the TBI group exhibited markedly increased reactions. Cytochrome c immunoreactivity appeared in a granular pattern within neurons of the DG region. In the MK-801 treatment group, both BAX and cytochrome c immunoreactivities were reduced compared to the TBI group. While only weak caspase-3 immunoreactivity was observed in the control group, intense immunoreactivity was detected in both the DG and CA1 regions of the hippocampus in the TBI group. In contrast, caspase-3 immunoreactivity was notably reduced in the MK-801 group compared to the TBI group.
Conclusion:
This study demonstrated that treatment with MK-801 significantly reduces apoptosis in the hippocampus by downregulating key pro-apoptotic markers, including BAX, cytochrome c and caspase-3. These findings suggest that MK-801 exerts a neuroprotective effect by interfering with the intrinsic apoptotic pathway following TBI.
