Work

Cathepsin B Inhibition Attenuates Acute Cerebral Ischemia-Reperfusion Injury and Suppresses Associated Apoptotic and Neuroinflammatory Responses

Year: 2026

Type: article

Abstract: Cerebral ischemia-reperfusion injury (CIRI) is driven by cell death and multiple secondary pathological responses, but its key regulatory mechanisms remain incompletely understood. Using a rat middle cerebral artery occlusion/reperfusion model and a PC12 cell oxygen-glucose deprivation/reoxygenation model, we investigated the role of cathepsin B (CTSB) in acute CIRI. CTSB inhibition markedly reduced cerebral infarct volume from 42.6% to 15.2% and restored cell viability from 45.2% to 82.5%. Genetic suppression of CTSB produced a comparable protective effect, further supporting its involvement in ischemia-reperfusion-induced injury. Temporal analyses revealed distinct expression patterns of CTSB, c-Jun N-terminal kinase 3, and BH3-interacting domain death agonist, while spatial and biochemical analyses suggested their association within the acute ischemia-reperfusion injury response. More importantly, the protective effects of CTSB inhibition extended beyond apoptosis, with concurrent attenuation of inflammatory responses, restoration of antioxidant defenses, and preservation of blood-brain barrier integrity. Together, these findings suggest that CTSB may serve as an important regulatory node linking cell death with multiple secondary injury processes and may represent a potential therapeutic target for acute CIRI.

Source: Inflammation

DOI: 10.1007/s10753-026-02639-8