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Updated: Apr 7, 2026
Evaluating Cell Death Signaling by Immunofluorescence in a Rat Model of Ischemic Stroke
Published on: January 3, 2025
Sur1-Trpm4 Cation Channel Expression in Human Cerebral Infarcts
Rupal I Mehta1, Cigdem Tosun, Svetlana Ivanova
1From the Departments of Pathology (RIM, RJC, JMS), Neurosurgery (SI, NT, MSK, VG, JMS), Neurology (BMF), and Physiology (JMS), University of Maryland School of Medicine, Baltimore, Maryland; and the Department of Molecular Biology and Genetics (CT), Izmir Institute of Technology, Izmir, Turkey.
Transient Receptor Potential Melastatin 4 (Trpm4) channels are upregulated after stroke, contributing to brain swelling and blood-brain barrier damage. Inhibiting these channels may offer a new therapeutic approach for ischemic stroke patients.
Area of Science:
- Neuroscience
- Cardiovascular Biology
- Cell Biology
Background:
- Transient Receptor Potential Melastatin 4 (Trpm4) channels are implicated in brain injury following stroke.
- Sur1-Trpm4 channels play key roles in cytotoxic and vasogenic edema, cell death, and blood-brain barrier disruption.
- Trpm4 is transcriptionally upregulated in neural and vascular cells in animal models of brain infarction.
Purpose of the Study:
- To investigate Trpm4 expression and its association with Sur1 in human postmortem brain specimens from focal cerebral ischemia patients.
- To determine the temporal expression of Trpm4 in the ischemic brain.
- To evaluate the therapeutic potential of targeting Sur1-Trpm4 channels in a preclinical stroke model.
Main Methods:
- Immunohistochemistry and in situ hybridization were used to analyze Trpm4 protein and mRNA expression in human brain tissue.
- Immunofluorescence and co-immunoprecipitation were employed to assess Trpm4 and Sur1 co-localization and association.
- A rat middle cerebral artery occlusion model was used to study the effects of glibenclamide, a Sur1 inhibitor, on stroke pathology.
Main Results:
- Increased Trpm4 protein and mRNA expression were observed in all human ischemic stroke specimens up to 1 month post-onset.
- Trpm4 colocalized and co-associated with Sur1 in ischemic endothelial cells and neurons, particularly in areas with vasogenic edema.
- Pharmacologic blockade of Sur1 channels with glibenclamide reduced perivascular tumor necrosis factor labeling in a rat stroke model.
Conclusions:
- Upregulation of Sur1-Trpm4 channels is a significant finding in human ischemic stroke.
- These channels are associated with blood-brain barrier disruption and cerebral edema.
- Targeting Sur1-Trpm4 channels represents a potential therapeutic strategy for managing cerebral ischemia.
