Vildagliptin improves neurological function by inhibiting apoptosis and ferroptosis following intracerebral hemorrhage in mice

Intracerebral hemorrhage (ICH) is a fatal health problem which lacks effective treatment. The apoptosis caused by hematoma constituents, and the ferroptosis due to iron overload, are prominent contributors of neurologic impairment after ICH. Targeting cell death pathways may thus be a therapeutic strategy for neuroprotection and functional recovery in ICH. Vildagliptin (Vilda), a dipeptidyl peptidase (DPP)-4 inhibitor, has been reported to have potent anti-apoptosis and anti-ferroptotic capacity. However, it is not clear whether Vilda has anti-cell death efficacy in ICH. In the present study, the potential neuroprotective effect of Vilda in ICH mice was investigated. Mice were randomly divided into three groups: sham, ICH + saline or ICH + Vilda. ICH was induced by collagenase type VII micro-injection into the right basal ganglia. Vilda (50 mg/kg/day; gavage) daily treatment for 3 days after ICH improved neurological deficit scores, reduced hematoma volume, and inhibited degeneration of neurons. The activation of microglia/macrophages and infiltration of neutrophil were restrained by Vilda. Moreover, Vilda attenuated brain cell apoptosis as determined by TUNEL staining, raised Bcl-2 protein level, and simultaneously suppressed Bax as validated by western blots. In addition, Vilda reduced malondial-dehyde level, elevated glutathione peroxidase brain content, and alleviated iron deposition at 3 days after ICH in mice. In conclusion, Vilda exerts neuroprotective effects in ICH, at least in part by inhibiting neuroinflammation, and preventing neuronal apoptosis and ferroptosis following ICH.

Automated summary

Intracerebral hemorrhage is a fatal health problem with limited treatment options. This study found that Vildagliptin, a DPP-4 inhibitor, exerts neuroprotective effects in intracerebral hemorrhage by inhibiting cell death pathways.