NMDA receptors antagonists alleviated the acute phase of traumatic brain injury

Document Type : Original Article

Authors

1 Qaen Faculty of Medical Science, Birjand University of Medical Sciences, Birjand, Iran

2 Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran

3 Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran

4 Department of Anatomy, School of Medicine, Iranshahr University of Medical Sciences, Iranshahr, Iran

5 Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

6 Department of Neuroscience, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

7 Department of Pharmaceutical Biomaterials, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

8 Department of Forensic Medicine, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

10.22038/ijbms.2024.80887.17500

Abstract

Objective(s): Traumatic brain injury (TBI) is a significant cause of mortality and disability worldwide. TBI has been associated with factors such as oxidative stress, neuroinflammation, and apoptosis, which are believed to be mediated by the N-methyl-D-aspartate (NMDA)-type glutamate receptor. Two NMDA receptor antagonists, ketamine and memantine, have shown potential in mitigating the pathophysiological effects of TBI.
Materials and Methods: To conduct the study, a controlled cortical impact model was used to induce TBI in rats. The rats with TBI were then divided into three groups: a group receiving only TBI, a group receiving TBI along with memantine, and a group receiving TBI along with ketamine. After 24 hr, the levels of oxidative stress markers (such as SOD, MDA, and total thiol) in the brain tissue were measured. Immunohistochemical staining was also performed seven days after TBI to assess the activation of glial cells and the TLR-4/NF-κB neuroinflammatory pathway.
Results: The results indicated that treatment with memantine led to a reduction in MDA levels and an increase in SOD and total thiol levels. Memantine also decreased astrogliosis and down-regulated the TLR-4/NF-κB pathway. On the other hand, ketamine increased the levels of anti-oxidant markers but did not significantly affect the MDA level. Additionally, ketamine decreased the expression of NF-κB seven days after TBI.
Conclusion: The findings suggest that NMDA receptor antagonists, such as ketamine and memantine, may have therapeutic effects on TBI by inhibiting oxidative stress and inflammatory responses. 

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences
Volume 28, Issue 2
February 2025
Pages 181-186

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