PMID- 23602966 OWN - NLM STAT- MEDLINE DCOM- 20140117 LR - 20130603 IS - 1872-6240 (Electronic) IS - 0006-8993 (Linking) VI - 1517 DP - 2013 Jun 23 TI - Alogliptin, a dipeptidylpeptidase-4 inhibitor, for patients with diabetes mellitus type 2, induces tolerance to focal cerebral ischemia in non-diabetic, normal mice. PG - 104-13 LID - S0006-8993(13)00528-3 [pii] LID - 10.1016/j.brainres.2013.04.015 [doi] AB - Effective interventions that provide obvious neuroprotection are currently fairly limited. Glucagon-like peptide-1 (GLP-1), an enhancer of insulin production with a trophic effect on beta cells in the islets, has been found to be trophic for neuronal cells. Alogliptin benzoate (AGL), a selective inhibitor of dipeptidylpeptidase-4 (DPP-4) functioning as a long-acting agonist of GLP-1, is in clinical use worldwide for patients with diabetes mellitus type 2. To clarify whether administration of AGL, independent of the insulinotropic effect, protects the brain against focal ischemia, we investigated the effect of AGL on the development of cerebral infarction in non-diabetic normal mice. Male C57BL/6J mice were administered AGL (7.5, 15, or 30mug) once a day for three weeks by intragastric gavage. After the induction of temporary focal ischemia, volumes of infarcted lesions and neurological deficits were analyzed at 24h (acute phase) and seven days (chronic phase). In the acute phase, significant reductions were observed in the volumes of infarcted lesions (p=0.009), and in the severity of neurological deficits (p=0.004), in the group treated with 15mug of alogliptin benzoate, but not the 7.5 or 30mug-treated groups. This significant reduction in volumes of infarcted lesions persisted into the chronic phase. At the end of the AGL treatment; before the induction of ischemia, the levels of brain-derived neurotrophic factor (BDNF), a potent neuroprotectant in the brain, were elevated in the cortex (p=0.008), or in the whole forebrain (p=0.023). AGL could be used as a daily neuroprotectant or an enhancer of BDNF production aiming to attenuate cerebral injuries, for the growing number of people who have the risk of ischemic stroke. CI - Copyright (c) 2013 Elsevier B.V. All rights reserved. FAU - Yang, Dong AU - Yang D AD - Laboratory of Neurology and Neurosurgery, National Cerebral and Cardiovascular Research Center, Suita 565-8565, Japan. FAU - Nakajo, Yukako AU - Nakajo Y FAU - Iihara, Koji AU - Iihara K FAU - Kataoka, Hiroharu AU - Kataoka H FAU - Yanamoto, Hiroji AU - Yanamoto H LA - eng PT - Journal Article DEP - 20130417 PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Piperidines) RN - 56HH86ZVCT (Uracil) RN - JHC049LO86 (alogliptin) SB - IM MH - Analysis of Variance MH - Animals MH - Brain Edema/etiology/prevention & control MH - Brain Infarction/etiology/prevention & control MH - Brain Ischemia/complications/*drug therapy/pathology/*prevention & control MH - Brain-Derived Neurotrophic Factor/metabolism MH - Dipeptidyl-Peptidase IV Inhibitors/*therapeutic use MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Gene Expression Regulation/drug effects MH - Laser-Doppler Flowmetry MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Microcirculation/physiology MH - Nervous System Diseases/etiology/prevention & control MH - Piperidines/*therapeutic use MH - Prosencephalon/blood supply/drug effects/metabolism MH - Time Factors MH - Uracil/*analogs & derivatives/therapeutic use EDAT- 2013/04/23 06:00 MHDA- 2014/01/18 06:00 CRDT- 2013/04/23 06:00 PHST- 2013/01/02 00:00 [received] PHST- 2013/04/05 00:00 [revised] PHST- 2013/04/08 00:00 [accepted] PHST- 2013/04/23 06:00 [entrez] PHST- 2013/04/23 06:00 [pubmed] PHST- 2014/01/18 06:00 [medline] AID - S0006-8993(13)00528-3 [pii] AID - 10.1016/j.brainres.2013.04.015 [doi] PST - ppublish SO - Brain Res. 2013 Jun 23;1517:104-13. doi: 10.1016/j.brainres.2013.04.015. Epub 2013 Apr 17.