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D-allose Attenuates Pyroptosis of Neurons after Cerebral ischemia-reperfusion injury via Regulation of the Gal-3/NLRP3 Pathway

      Abstract

      Objective: Cerebral ischemia-reperfusion injury (CIRI) is a particularly severe pathological condition that arises when blood is restored to an injured area after cerebral ischemia. Neuronal cell death stands out as the most severe detrimental outcome of CIRI. Therefore, it is critical to explore neuroprotective strategies following CIRI. This study aimed to assess the potential neuroprotective effects of D-allose in the context of CIRI by targeting the Gal-3/NLRP3 pathway and reducing neuronal cell death. Methods: In this study, we employed a middle cerebral artery occlusion (MCAO) model that included pretreatment with D-allose. Assessment of MCAO injury included behavioral analysis, neurological function scoring, and triphenyl tetrazolium chloride (TTC) staining. Apoptosis following CIRI and D-allose treatment was determined using TUNEL. Furthermore, we examined the expression of pyroptosis related molecules and Gal-3 using q-PCR, Western Blotting, and immunofluorescence staining. Results: Behavioral analysis, neurological function scoring and TTC staining, revealed that pretreatment with D-allose alleviated MCAO-induced brain injury. Additionally, D-allose treatment was associated with reduced expression of pyroptosis-related molecules and Gal-3 following CIRI. In the MCAO+AAV-shGal-3 group, wherein Gal-3 expression was down-regulated, the expression of pyroptosis-related molecules was lower compared to the MCAO+NC group. However, D-allose treatment did not further enhance this reduction. Conclusions: These findings strongly indicate that D-allose might play a neuroprotective role in CIRI by downregulating Gal-3 expression, thereby inhibiting activation of the pyroptosis pathway.