Non-invasively triggered spreading depolarizations induce a rapid pro-inflammatory response in cerebral cortex

Area of Science:

• Neuroscience
• Neuroinflammation
• Molecular Biology

Background:

• Cortical spreading depolarization (CSD) is linked to neuroinflammation.
• Previous studies used invasive methods, confounding results with direct inflammation induction.
• A non-invasive method is needed to study CSD-induced inflammation.

Purpose of the Study:

• To investigate pro-inflammatory gene expression following non-invasively induced CSD.
• To differentiate CSD-induced inflammation from injury-related inflammation.
• To explore the upstream mediators and potential treatments for CSD-induced neuroinflammation.

Main Methods:

• Optogenetics was used for non-invasive CSD induction in Thy1-channelrhodopsin-2 mice.
• Minimally invasive KCl-induced CSDs were used for corroboration.
• mRNA expression of key inflammatory genes was measured using RT-qPCR.

Main Results:

• Non-invasive CSD significantly increased cortical interleukin-1β (IL-1β), CCL2, and TNF-α mRNA expression.
• A single CSD induced an ultra-early IL-1β response within 10 minutes.
• IL-1β was identified as an upstream mediator, with dexamethasone suppressing the response.

Conclusions:

• Non-invasive CSD induction reliably triggers pro-inflammatory gene expression in the brain.
• CSD-induced neuroinflammation plays a role in migraine pathogenesis.
• These findings have implications for understanding inflammatory processes in acute brain injury.