PATHOPHYSIOLOGY OF CEREBRAL EDEMA IN STROKE:
- Following ischemic insult, SUR1-TRPM4 ion channel expressed in all cells of the neurovascular unit.
- Early stages of ischemia, channel upregulation occurs at the luminal and abluminal surfaces of the vascular endothelium, mediating an ionic gradient from the intraluminal space to the interstitial space.
- Water transported from vasculature into the parenchyma.
- Formation of ionic gradient followed by or accompanied by breakdown of the BBB.
- Capillary structure is maintained, preventing extravasated of cells, while vasculature becomes open to water movement and movement of macromolecules s.a. Immunoglobulin / albumin.
- Opening facilitates osmotic and hydrostatic movement of water into brain.
- Tight junctions between vascular endothelial cells degraded by MMP9, which further facilitates fluid movement into the brain.
MECHANISM OF ACTION OF GLIBENCLAMIDE
- Glibenclamide is an anti-edema drug.
- Glibenclamide blocks the activity of the SUR1-TRPM4 ion channel.
- This channel is upregulated in the CNS only after ischemia / trauma.
- Glibenclamide blocks this cascade, protects the neurovascular unit.
- First impact is on the capillary endothelium, rather than neurons.
- Glibenclamide does not cross the uninjured BBB, only the channels up-regulated in the vascular endothelium are relevant until such time as the BBB is disrupted.
Jacobson, S., MacAllister, T. and Geliebter, D., 2020. Found in translation: The rationale behind the early development of glibenclamide in large hemispheric infarction. Neuroscience Letters, 716, p.134672.