Protective Effects of MK-801 on Apoptosis in Immature Rats With Traumatic Brain Injury
International Journal of Developmental Neuroscience, vol.85, no.5, 2025 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 85 Issue: 5
- Publication Date: 2025
- Doi Number: 10.1002/jdn.70043
- Journal Name: International Journal of Developmental Neuroscience
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
- Keywords: apoptosis, MK-801, traumatic brain injury
- Dokuz Eylül University Affiliated: Yes
Abstract
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.