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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\u2010CCI treatment with sitagliptin, but not vildagliptin, significantly reduced body asymmetry, locomotor hyperactivity, and brain lesion volume. Sitagliptin attenuated post\u2010CCI microglial deramification in the ipsilateral dorsolateral (DL) striatum, while vildagliptin had no effect. Sitagliptin also reduced striatal expression of galectin\u20103 and monocyte chemoattractant protein 1(MCP\u20101), and increased the cortical and striatal levels of the anti\u2010inflammatory cytokine IL\u201010 on the ipsilateral side. These data support a differential protective effect of sitagliptin against TBI, possibly mediated by an anti\u2010inflammatory effect in striatum to preserve connective network. Both sitagliptin and vildagliptin produced similar increases of active glucagon\u2010like peptide\u20101 (GLP\u20101) in blood and brain. Increasing active GLP\u20101 may not be the sole molecular mechanisms for the neurotherapeutic effect of sitagliptin in TBI.<\/jats:p>","DOI":"10.1096\/fj.201902818r","type":"journal-article","created":{"date-parts":[[2020,4,4]],"date-time":"2020-04-04T10:09:22Z","timestamp":1585994962000},"page":"6950-6964","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["DPP\u20104 inhibitor reduces striatal microglial deramification after sensorimotor cortex injury induced by external force impact"],"prefix":"10.1096","volume":"34","author":[{"given":"Yu\u2010Wen","family":"Hung","sequence":"first","affiliation":[{"name":"Institute of Cellular and System Medicine National Health Research Institutes Zhunan Town, Miaoli County Taiwan, R.O.C."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Neuropsychiatric Research National Health 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