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Neuroprotective effects of MK-801 against cerebral ischemia reperfusion
Zahra Yaghoobi1,2, Saeid Ataei3, Esmail Riahi1
1Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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.
Insights
MK-801 treatment improves survival of hippocampal neurons following cerebral ischemia/reperfusion (I/R) injury. This neuroprotective effect involves increased neuroplasticity and neuronal activity, suggesting therapeutic potential for brain injury.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Cerebral ischemia/reperfusion (I/R) injury is a leading cause of global mortality.
- NMDA receptor overactivation contributes to neuronal damage in I/R injury.
- Targeting NMDA receptors may offer a therapeutic strategy for brain injury.
Purpose of the Study:
- To investigate the role of NMDA receptors in hippocampal neuronal activity during I/R.
- To evaluate the neuroprotective effects of MK-801, an NMDA receptor antagonist, in a rat model of cerebral I/R injury.
Main Methods:
- Wistar rats underwent sham surgery or cerebral I/R induction.
- Groups received either MK-801 (NMDA receptor antagonist) or NMDA.
- Histological analysis (Nissl, H&E) assessed neuronal survival and morphology.
- Western blot measured BDNF, p-CREB, and c-fos expression.
- Single unit recording evaluated CA1 pyramidal neuron activity.
Main Results:
- Cerebral I/R induced significant CA1 pyramidal neuron damage.
- MK-801 treatment improved neuronal survival and morphology post-I/R.
- MK-801 increased BDNF, c-fos, and p-CREB levels and decreased cleaved caspase-3.
- Electrophysiological recordings showed MK-801 enhanced CA1 pyramidal neuron firing rates.
Conclusions:
- MK-801 demonstrates significant neuroprotective effects against cerebral I/R injury.
- The drug enhances cell survival, upregulates neuroplasticity markers, and increases neuronal firing.
- MK-801 shows promise as a therapeutic agent for cerebral I/R-induced brain injury.
