Orlandini for animal care, Henrique B. Biehl and Carlos E. L. Santos for their assistance with confocal microscopy (Centro de Microscopia Eletrônica da UFRGS). Technical assistance

was provided by Silvia Barbosa and Antônio Severino. We also thank Ana Paula Horn and Lauren Valentim for their helpful information in immunofluorescence. This study was supported by grants from CNPq and CAPES. There was no conflict of interests. “
“For the growing number of people who have the risk of, or experienced cerebral infarction or TIA (Weimar et al., 2010 and Hata et al., 2005), development of a novel compound to protect neurons from click here focal ischemia, or even to promote cerebral repair, is urgently required. In the incretin family, glucagon-like peptide-1 (GLP-1), or insulinotropic UK-371804 mouse secreted from L cells in the gastrointestinal tract as a response to food ingestion (Cefalu, 2010 and Rizzo et al., 2009), acts as a trophic factor for β cells in the islets by enhancing insulin biosynthesis/release and their proliferation ( Turton et al., 1996). In addition to the β cell-trophic/insulinotropic

effect, GLP-1 exerts a neurotrophic effect in the brain ( McClean et al., 2010 and Perry et al., 2002). Indeed, GLP-1 can enter the brain; the GLP-1 receptors (GLP-1R) is expressed widely in the central nervous system ( During et al., 2003 and Turton et al., 1996); and the activation of GLP-1R was found to improve cognitive performance ( Li et al., 2010a and During et al., 2003). However, once secreted Acyl CoA dehydrogenase into the blood, GLP-1 is rapidly degraded and inactivated following release

of the intrinsic antagonizing enzyme, dipeptidylpeptidase-4 (DPP-4). Exendin-4 (Ex-4), a long-acting analog of GLP-1 (a GLP-R agonist), developed for intravenous treatment of type II diabetes mellitus (DM-2), demonstrated a neuroprotective property in vivo after cerebro-ventricular administration (Li et al., 2009). Ex-4 also exerted a neurotrophic property in vitro (Li et al., 2010c). Moreover, in a transgenic mouse model of Alzheimer’s disease (AD) combined with streptozocin-induced DM-2, a continuous subcutaneous injection of Ex-4 reduced the levels of amyloid-β (Aβ) protein in the brain ( Li et al., 2010b). Alogliptin benzoate (AGL), a potent and highly selective inhibitor of DPP-4, developed for once-daily oral treatment of DM-2, demonstrated a lower incidence of unfavorable side effects such as hypoglycemia and hyperphagia, compared to previous drugs (Moritoh et al., 2008 and Feng et al., 2007). Although treatment with AGL for a prolonged period in DM-2 patients is expected to protect β cells and prevent atherosclerotic vascular damage, it is unknown whether AGL, independent of its insulinotropic properties, protects neurons against lethal ischemia.