{"title":"Protective Effects of MK-801 on Apoptosis in Immature Rats With Traumatic Brain Injury.","authors":"Ayşe Çiğel, Oya Sayın, Seren Gülşen Gürgen, Talha Başar Koç, Ataç Sönmez","doi":"10.1002/jdn.70043","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":13914,"journal":{"name":"International Journal of Developmental Neuroscience","volume":"85 5","pages":"e70043"},"PeriodicalIF":1.6000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Developmental Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/jdn.70043","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"DEVELOPMENTAL BIOLOGY","Score":null,"Total":0}
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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.
期刊介绍：
International Journal of Developmental Neuroscience publishes original research articles and critical review papers on all fundamental and clinical aspects of nervous system development, renewal and regeneration, as well as on the effects of genetic and environmental perturbations of brain development and homeostasis leading to neurodevelopmental disorders and neurological conditions. Studies describing the involvement of stem cells in nervous system maintenance and disease (including brain tumours), stem cell-based approaches for the investigation of neurodegenerative diseases, roles of neuroinflammation in development and disease, and neuroevolution are also encouraged. Investigations using molecular, cellular, physiological, genetic and epigenetic approaches in model systems ranging from simple invertebrates to human iPSC-based 2D and 3D models are encouraged, as are studies using experimental models that provide behavioural or evolutionary insights. The journal also publishes Special Issues dealing with topics at the cutting edge of research edited by Guest Editors appointed by the Editor in Chief. A major aim of the journal is to facilitate the transfer of fundamental studies of nervous system development, maintenance, and disease to clinical applications. The journal thus intends to disseminate valuable information for both biologists and physicians. International Journal of Developmental Neuroscience is owned and supported by The International Society for Developmental Neuroscience (ISDN), an organization of scientists interested in advancing developmental neuroscience research in the broadest sense.
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