Journal
FASEB JOURNAL
Volume 34, Issue 5, Pages 6950-6964Publisher
WILEY
DOI: 10.1096/fj.201902818R
Keywords
controlled cortical impact; dorsolateral striatum; microglial ramification; sitagliptin; traumatic brain injury; vildagliptin
Categories
Funding
- National Health Research Institutes (NHRI) [06A1-CSPP10-014,07A1-CSPP10-014]
- Taiwan Central Govement ST [06A1-NPSP06-034,07A1-NPSP11-034]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available