pH and proton-sensitive receptors in brain ischemia.

Area of Science:

• Neuroscience
• Molecular Biology
• Pathophysiology

Background:

• Extracellular proton concentration increases significantly during brain ischemia.
• Mammalian brains express various proton receptors, including acid-sensing ion channels (ASICs) and proton-sensitive G protein-coupled receptors (GPCRs).
• Recent evidence highlights the functional importance of GPCRs (GPR4, GPR65, GPR68) in brain injury.

Purpose of the Study:

• To review recent findings on the differential contribution of proton-sensitive GPCRs to brain acid signaling.
• To elucidate the role of these GPCRs in cerebrovascular function, neuroinflammation, and neuronal injury following acidosis and brain ischemia.

Main Methods:

• Literature review of recent findings on proton-sensitive GPCRs in the brain.
• Analysis of differential expression patterns of GPR4, GPR65, and GPR68 in brain cells (endothelium, microglia, neurons).

Main Results:

• GPR4 is highly expressed in brain endothelium.
• GPR65 is found in a subset of microglia.
• GPR68 is predominantly expressed in brain neurons.

Conclusions:

• Proton-sensitive GPCRs play differential roles in brain acid signaling.
• These receptors are crucial in modulating cerebrovascular function, neuroinflammation, and neuronal injury during ischemic events.
• Understanding these mechanisms can inform therapeutic strategies for brain ischemia.