EGR1-associated inflammatory and neurovascular signatures suggest a potential link between migraine and ischemic stroke.

Migraine increases the risk of ischemic stroke, but the mechanisms are unclear. This study analyzed RNA-seq data from ischemic stroke and a mouse migraine model. Researchers aimed to identify shared molecular signatures and pathways. A nitroglycerin-induced migraine mouse model validated neurovascular changes in vivo. The analysis found shared upregulated genes in both conditions, including IL1B and EGR1. Key pathways involved immune and inflammatory responses, particularly signaling related to interleukin-1. Single-cell analysis revealed EGR1 as the only significantly shared gene in migraine. Elevated expression was observed in various cell types, including neurons and fibroblasts. Enhanced cell interactions were discovered among neuronal, vascular, and fibroblast populations through ANGPTL signaling. The migraine model showed increased neuronal activation and reduced ZO-1 expression, indicating vascular impairment. These findings suggest inflammatory and neurovascular connections between migraine and ischemic stroke. Further studies are necessary to explore EGR1's potential role in these pathways. Clinical relevance: This research highlights potential inflammatory links between migraine and ischemic stroke, guiding future treatment approaches.