The Role of Neuroinflammation: Dissecting the Relationship between Aura and Brain Inflammation
Our team’s recent findings, soon to be published, have identified a novel discovery: people with migraine with aura exhibit clear signs of brain inflammation. This insight was derived from advanced neuroimaging and the detection of increased blood levels of the inflammatory marker soluble urokinase plasminogen activator receptor (uPAR). These findings align with decades of preclinical studies indicating that neuroinflammation plays a role in migraine with aura, particularly within the visual cortex However, the specific cellular and molecular mechanisms underlying these changes remain poorly understood.
To further explore these recent insights, we plan on using positron emission tomography (PET) to map brain activity of uPAR – an inflammatory receptor found on activated macrophages and microglia. We will use Ga-NOTA-AE105, a uPAR tracer to compare its uptake among people with migraine with aura, those with migraine without aura, and healthy controls. In addition, we will also examine alterations in tracer uptake during provoked migraine attacks with aura.
Sub-projects exploring neuroinflammation
Sub-Project 7: uPAR Expression in Migraine with Aura and Control Populations
Objective:
To identify increases in uPAR activity associated with migraine with aura and distinct from migraine without aura and healthy controls.
Potential Significance:
Demonstrating distinct macrophagic and microglial responses specific to migraine with aura in neuroinflammation can bridge the gap between preclinical and clinical aura models. This might also shed light on the mechanisms that predispose individuals to aura attacks and potentially link aura occurrence to the subsequent onset of migraine pain. These insights will be instrumental in guiding the development of targeted treatments for both migraine aura and pain.
Sub-Project 8: uPAR Expression Before and After Provoked Migraine Aura
Objective:
Due to the unpredictable nature of spontaneous migraine auras, we aim to examine uPAR tracer activity by inducing provoked migraine aura using CGRP infusion.
Potential Significance:
Identifying an increase in neuroinflammation, particularly within the visual cortex and overlying parameningeal tissues post-aura, provides unique evidence that links clinical symptoms to specific pathophysiological processes. These insights might offer clues into how migraine aura and its neurobiological substrate is related to the pathogenesis of migraine pain.