Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Neuroprotective Effects of Mk-801 Against Cerebral Ischemia Reperfusion Publisher



Yaghoobi Z1, 2 ; Ataei S3 ; Riahi E1 ; Parviz M1 ; Sehati F1 ; Zare M4 ; Angizeh R5 ; Ashabi G1, 3, 6 ; Hosseindoost S7, 8
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Division of Neurobiology, Faculty of Biology, Ludwig-Maximilians-Universitat Munchen, Munchen, Germany
  3. 3. Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
  5. 5. Department of Exercise Physiology & Health, Faculty of Exercise Sciences, Shahid Rajaee Teacher Training University, Tehran, Iran
  6. 6. Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Pain Research Center, Neuroscience Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

Source: Heliyon Published:2024


Abstract

Introduction: & Objective: Cerebral ischemia/reperfusion (I/R) injury, the second cause of death globally, involves increased NMDA receptor activity leading to neuronal damage due to excessive sodium and calcium ion entry. Therefore, targeting NMDA receptor may potentially reduce cell death induced by brain injury. Our study aimed to investigate the role of NMDA receptors in hippocampal neuronal activity induced by I/R. Methods: In this study, Wistar rats were divided into four groups: sham, I/R, I/R + MK801, and I/R + NMDA. Cerebral I/R injury was induced by temporarily occluding the common and vertebral carotid arteries, followed by reperfusion. MK801 or NMDA was administered to the rats after a specific reperfusion time. Neuronal density and cell morphology in the hippocampal CA1 region were assessed using Nissl and H&E staining. The expression of BDNF, p-CREB, and c-fos was evaluated through Western blot analysis. Additionally, neuronal activity in CA1 pyramidal neurons were examined using single unit recording technique. Results: Our results showed that cerebral I/R injury caused significant damage to CA1 pyramidal neurons compared to the sham group. However, treatment with MK-801 improved hippocampal cell survival compared to the I/R group. Furthermore, MK-801 administration in I/R rats increased BDNF, c-fos, and p-CREB levels while decreasing cleaved caspase-3 activity compared to the I/R group. Additionally, electrophysiological data showed that MK-801 increased firing rates of CA1 pyramidal neurons during the reperfusion phase. Conclusion: MK-801 shows promise as a therapeutic agent for cerebral I/R injury by enhancing cell survival, upregulating neuroplasticity factors, and increasing firing rates of CA1 pyramidal neurons. It exerts a specific protective effect against cerebral I/R injury. © 2024 The Authors
Related Docs
1. The Neuroprotective Mechanisms of Kaempferol in Experimental Ischemic Stroke: A Preclinical Systematic Review, Molecular Neurobiology (2025)
2. Circulating Brain-Derived Neurotrophic Factor As a Potential Biomarker in Stroke: A Systematic Review and Meta-Analysis, Journal of Translational Medicine (2022)
3. Dexmedetomidine Administration As a Possible Cognitive Enhancer Through Increasing the Level of Brain-Derived Neurotrophic Factors in Surgical Patients: A Systematic Review and Meta-Analysis, BMC Anesthesiology (2024)
4. Nmda Receptor Adjusted Co-Administration of Ecstasy and Cannabinoid Receptor-1 Agonist in the Amygdala Via Stimulation of Bdnf/Trk-B/Creb Pathway in Adult Male Rats, Brain Research Bulletin (2017)
Experts (# of related papers)
Nima Rezaei (1)
Ghorbangol Ashabi (1)