Microglia Modulate Cortical Spreading Depolarizations After Ischemic Stroke: A Narrative Review

Area of Science:

• Neuroscience
• Neurocritical Care
• Neuroimmunology

Background:

• Cortical spreading depolarizations (CSDs) are waves of suppressed brain activity linked to poor outcomes in conditions like ischemic stroke.
• CSDs cause ionic and metabolic disruptions in the brain's peri-infarct zone, potentially worsening stroke-related tissue damage.
• Microglia, the brain's primary immune cells, are increasingly recognized for their role in CSD initiation and propagation.

Purpose of the Study:

• To review the role of CSDs in ischemic stroke.
• To explore how microglia modulate peri-infarct CSDs (iso-electric depolarizations).
• To discuss microglial calcium signaling as a potential therapeutic target for stroke.

Main Methods:

• Literature review and synthesis of recent studies on CSDs and microglia in ischemic stroke.
• Discussion of the pathophysiological mechanisms linking CSDs, microglia, and stroke outcomes.
• Exploration of microglial calcium dynamics as a therapeutic avenue.

Main Results:

• CSDs are implicated in exacerbating infarction and worsening clinical outcomes following ischemic stroke.
• Microglia play a significant role in the initiation and propagation of CSDs, particularly in the peri-infarct region.
• Microglial calcium signaling represents a promising target for mitigating CSD-associated damage in stroke.

Conclusions:

• CSDs are a significant factor in ischemic stroke pathology, contributing to infarct expansion and poorer outcomes.
• Targeting microglial function, specifically their calcium signaling pathways, may offer a novel therapeutic strategy to reduce CSD-induced brain damage after stroke.