NMDA receptors antagonists alleviated the acute phase of traumatic brain injury.
Mehrdad Hajinejad, Ahmadreza Gharaeian Morshed, Abdolreza Narouiepour, Maryam Izadpanahi, Mohammad Mahdi Taheri, Mohammad Hossein Sadeghian, Fatemeh Forouzanfar, Sajad Sahab Negah
Iranian journal of basic medical sciences January 1, 2025 DOI: 10.22038/ijbms.2024.80887.17500 via PubMed
Summary
AI-generated from the abstractIn a rat model of traumatic brain injury, two NMDA receptor antagonists, memantine and ketamine, each reduced aspects of brain damage. Memantine lowered a marker of oxidative damage (MDA), raised antioxidant levels (SOD and total thiol), and suppressed both astrogliosis and the TLR-4/NF-κB inflammatory pathway. Ketamine increased antioxidant markers but did not significantly affect MDA; it also decreased NF-κB expression seven days after injury. These findings suggest that both drugs may protect the brain after trauma by curbing oxidative stress and inflammation.
Study at a glance
| Characteristics | Controlled animal experiment Peer reviewed |
|---|---|
| Population | Rats with traumatic brain injury induced by controlled cortical impact |
| Interventions | Memantine Ketamine |
| Duration | 24 hours for oxidative stress markers, 7 days for immunohistochemical staining |
| Topics | Ketamine |
| Keywords | Memantine Neuroinflammation Oxidative stress Traumatic brain injury |
| Citations | 1 |
| Key finding | Both memantine and ketamine reduced oxidative stress and inflammation after traumatic brain injury in rats, though memantine had a broader effect on oxidative markers and inflammatory pathways. |
Abstract
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. 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. 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. 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.