Dipeptidyl Peptidase-4 deficiency effectively protects the brain and neurological function in rodent after acute Hemorrhagic Stroke

Abstract

This study tested the hypothesis that abrogated dipeptidyl peptidase-4 (DPP4) activity played a crucial role on reducing stroke volume and preserving neurological function in rodent after acute hemorrhagic stroke (AHS). Animals (n=6/each group) were categorized into group 1 (sham-control of F344 rat), group 2 (sham-control of DPP4-deficiency rat), group 3 [AHS by right cerebral injection of autologous blood (100 µL) in F344 rat], group 4 (AHS + sitagliptin/600 mg/kg 3 h prior to and at 3 h then once per day after AHS) and group 5 (AHS in DPP4-deficiency rat). The results of corner test showed the neurological function was significantly improved from days 3, 7, and 14 in groups 4 and 5 than in group 3 (all p<0.001). By days 1 and 14 after AHS procedure, the circulating levels of SDF-1α and GLP-1 were significantly increased from groups 1/2 to group 5 (all p<0.001), whereas circulating DPP4 activity was significantly increased in group 3 than other groups (all p<0.001). The brain ischemic area (BIA) was highest in group 3, lowest in groups 1/2 and significantly lower in group 5 than in group 4 (all p<0.0001). The protein expressions of oxidative-stress/inflammatory/apoptotic/cell-proliferation signaling, and the cellular expressions of inflammatory/DNA-damaged biomarkers exhibited a similar pattern to BIA among the groups (all p<0.01). In conclusion, deprivation of DPP4 activity protected the brain from AHS damage and preserved neurological function.

Omarigliptin Protects the Integrity of the Blood–Brain Barrier After Intracerebral Hemorrhage in Mice

“…36 DPP4 deficiency effectively protects the brain and neurological function in rodent after ICH. 37 MK3102 is a potent DPP4 inhibitor. The expression of DPP4 was prominently reduced by MK3102 in ICH mice.…”

Anagliptin alleviates lipopolysaccharide‑induced inflammation, apoptosis and endothelial dysfunction of lung microvascular endothelial cells

“…Dipeptidyl peptidase-4 (DPP4), also known as CD26, is a widely expressed serine membrane-anchored peptidase that exists on the surface of various types of cell (7). Its expression level varies from cell to cell (8,9). In different organs and tissues (such as lung, muscle and heart), DPP4 activity is associated with its presence in the microvasculature (10).…”

CD26 and Cancer

“…In our study, we have demonstrated that individuals with angiodysplasia showed higher sCD26 and soluble DPP4 levels [ 49 ]. The presence in endothelial cells (also rich in CD26 [ 20 ]) of PAR-2, enhances angiogenesis on one hand [ 55 , 56 ] (CCL2 expression is also induced by soluble DPP4 [ 25 ]), and the well-known role of DPP4 activity in degrading pro-angiogenic chemokines, on the other [ 57 , 58 , 59 ], is a further unresolved issue probably with profound impacts in cancer treatment [ 24 ].…”