Details

Autor(en) / Beteiligte

• Urday, Sebastian
• Sheth, Kevin N.
• Simard, J. Marc

Titel

Chapter 10 - Sur1–Trpm4-Promising Target for Brain Edema Treatment in Brain Edema: From Molecular Mechanisms to Clinical Practice

Ist Teil von

• Brain Edema, 2017, p.183-198

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2017

Link zum Volltext

Beschreibungen/Notizen

• Brain edema after acute neurological injury causes significant morbidity and mortality. In this chapter, we highlight the critical role of the sulfonylurea receptor 1–transient receptor potential M4 (SUR1–TRPM4) channel in the pathogenesis of brain edema across various neurocritical care conditions. We emphasize that SUR1–TRPM4 activation is pivotal at every stage in edema formation. It contributes to every type of edema (cytotoxic, ionic, and vasogenic) and to total microvascular failure, which results in the extravasation of blood and the formation of petechial hemorrhages. We present examples from experimental models that demonstrate that selective blockade of SUR1–TRPM4 with glibenclamide results in improvement in edema, lesion volume, mortality, and neurological function. Clinical studies supporting the role of SUR1–TRPM4 in edema formation in humans are also presented. Although definitive phase III studies are needed, the ability to block SUR1–TRPM4 over a broad time window with a safe medication (glibenclamide) is emerging as a highly promising approach to treat brain edema.