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DPP‐4 inhibitor reduces striatal microglial deramification after sensorimotor cortex injury induced by external force impact
Author(s) -
Hung YuWen,
Wang Yun,
Lee SheauLing
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201902818r
Subject(s) - sitagliptin , vildagliptin , traumatic brain injury , neuroprotection , dipeptidyl peptidase 4 , medicine , striatum , endocrinology , neuroinflammation , dipeptidyl peptidase 4 inhibitor , central nervous system , blood–brain barrier , pharmacology , chemistry , inflammation , diabetes mellitus , dopamine , type 2 diabetes , psychiatry
Dipeptidyl peptidase‐4 inhibitors (or gliptins), a class of antidiabetic drugs, have recently been shown to have protective actions in the central nervous system. Their cellular and molecular mechanisms responsible for these effects are largely unknown. In the present study, two structurally different gliptins, sitagliptin and vildagliptin, were examined for their therapeutic actions in a controlled cortical impact (CCI) model of moderate traumatic brain injury (TBI) in mice. Early post‐CCI treatment with sitagliptin, but not vildagliptin, significantly reduced body asymmetry, locomotor hyperactivity, and brain lesion volume. Sitagliptin attenuated post‐CCI microglial deramification in the ipsilateral dorsolateral (DL) striatum, while vildagliptin had no effect. Sitagliptin also reduced striatal expression of galectin‐3 and monocyte chemoattractant protein 1(MCP‐1), and increased the cortical and striatal levels of the anti‐inflammatory cytokine IL‐10 on the ipsilateral side. These data support a differential protective effect of sitagliptin against TBI, possibly mediated by an anti‐inflammatory effect in striatum to preserve connective network. Both sitagliptin and vildagliptin produced similar increases of active glucagon‐like peptide‐1 (GLP‐1) in blood and brain. Increasing active GLP‐1 may not be the sole molecular mechanisms for the neurotherapeutic effect of sitagliptin in TBI.