ABS 047: Effects of Astrocytic Metabolic Dysfunction and Glucose Stress on Gene Expression During Cortical Spreading Depression

Shahmeer Khan ¹

¹ Wayne State University

The Van Wickle Journal (2026) Volume 2, ABS047

Introduction: Cortical Spreading Depression (CSD) is a propagating wave of neuronal depolarization that has been underlined with migraine aura, epilepsy, and contributes to secondary injury in neurological disorders. Previous studies have shown that CSD severity is influenced by astrocytic ion regulation and metabolic state, and that genes such as Fos, Ptgs2, Hmox1, and Prkcd are altered during CSD events. However, it remains unclear whether gene expression changes associated with CSD are driven primarily by acute depolarization events or by underlying astrocytic metabolic dysfunction.

Methods: In this study, transcriptomic analyses were performed to compare cortical spreading depression under two specific conditions within rodent populations: astrocyte-specific deletion of the Na+/K+-ATPase subunit Atp1a2 and surgically induced cortical spreading depression.

Results: The analysis revealed that gene expression changes associated with cortical spreading depression differ depending on metabolic context. Astrocyte-specific Atp1a2 deletion resulted in significant alterations in stress and activity-related genes (FosB, Hmox1). Acute CSD induction under glucose stress did not produce comparable transcriptional changes.

Discussion: These results suggest that chronic astrocytic metabolic dysfunction, rather than acute depolarization alone, may prime cortical tissue for altered CSD susceptibility. By emphasizing metabolic and astrocyte-specific mechanisms, this study provides a framework for future efforts towards therapeutic strategies aimed at reducing CSD susceptibility in migraine and other neurological disorders.