Glucocorticoid Alleviates Stress-induced Hypothalamic Nerve Injury by Inhibiting the GSDMD-dependent Pyroptosis Pathway

Background: Excessive stress leads to stress injury but the underlying mechanism is not completely understood and current preventive protocols are inadequate. This study aimed to investigate if glucocorticoid (GC) reduces nerve damage in the hypothalamus caused by stress and to clarify the mechanisms involved. Methods: Behavioral alterations in stressed rats were observed using the open field test. Changes in the levels of stress hormones, inflammatory factors, and stress-related injury factors were detected using enzyme-linked immunosorbent assay (ELISA). Pathological alterations in the hypothalamus were observed using thionine staining and hematoxylin & eosin (HE) staining. The expression levels of proteins linked to pyroptosis were determined using western blotting. Results: Stressed rats presented obvious anxiety-like behavior; the levels of stress hormones, inflammatory factors, and injury-related factors fluctuated abnormally. Morphological findings indicated substantial damage in the hypothalamus. Stress-induced nerve injury was alleviated by low-dose GC treatment, which also dramatically decreased the concentrations of inflammation-associated markers and expression of the gasdermin D (GSDMD)-related pyroptosis pathway. Conclusions: Low-dose GC alleviates hypothalamic nerve injury by inhibiting the GSDMD-dependent pyroptosis pathway in stressed rats.