Unraveling the Role of α2δ-1 in Cerebral Hemorrhage: Calcium Overload, Endoplasmic Reticulum Stress, and Microglial Apoptosis

Abstract

Objective

Cerebral hemorrhage is a severe condition associated with high morbidity and mortality. Understanding the underlying pathogenesis is crucial for developing effective therapeutic strategies. This study aimed to investigate the role of the dysregulated α2δ-1 protein in cerebral hemorrhage.

Materials and Methods

We observed a significant upregulation of α2δ-1 in cerebral hemorrhage tissue. Knockdown of α2δ-1 resulted in decreased intracellular calcium concentration and reduced phosphorylation of PLCr and IP3R in the presence of calcium. Additionally, α2δ-1-mediated calcium overload induced ERS in BV2 microglia, accompanied with increased phosphorylation of PERK and decreased ERS-related protein levels.

Results

α2δ-1 knockdown significantly inhibited BV2 microglia apoptosis and downregulated apoptosis-related proteins in the presence of calcium. Our study indicates the involvement of α2δ-1 in calcium-mediated signaling, endoplasmic reticulum stress, and BV2 microglia apoptosis.

Conclusions

The findings provide a basis for considering α2δ-1 as a potential therapeutic target in cerebral hemorrhage and secondary brain injury conditions associated with calcium dysregulation.