title: Telmisartan-mediated metabolic profile conferred brain protection in diabetic hypertensive rats as evidenced by magnetic resonance imaging, behavioral studies and histology.
abstract: Type 2 diabetes and hypertension are associated with cognitive dysfunction that includes pathological changes in brain tissue. It was speculated that the beneficial hypotensive effect of telmisartan, an angiotensin receptor 1 blocker, and its unique hypoglycemic effect due to its PPARγ-activation, could ameliorate the ​ pathological changes in the brain​ that accompany​ these diseases. We examined the effect of telmisartan on brain changes in magnetic resonance imaging (MRI) T2-weighted scans, and behavioral and histological findings in the Cohen-Rosenthal Diabetic Hypertensive (CRDH) rat. Baseline and post-treatment values with telmisartan/vehicle (3 months) of blood pressure, blood glucose levels, behavioral tests, brain MRI scanning and immunohistological staining were obtained. Telmisartan significantly lowered blood pressure and blood glucose levels; induced consistent T2 reduction in specific gray and white regions including hippocampus, corpus callosum, amygdala and cortical regions; and significantly improved performance on behavioral tasks. Immunohistological analysis of the brain revealed significant amelioration of diabetes/hypertension-induced changes in white matter regions and microglia, evidenced by preserved myelin (LBF marker), and improved microglial neuronal markers GFAP, GAP43 and Iba1 expression. In conclusion, the behavioral performance, longitudinal MRI study and histology staining revealed the protective effects of telmisartan on brain microstructure and cognitive function.
authors.affiliation: Hypertension Research Unit, Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Israel.
authors.forename: Firas M
authors.initials: FM
authors.lastname: Younis
authors.affiliation: Department of Neurobiology, Faculty of Life Sciences, Tel Aviv University, Israel.
authors.forename: Tamar
authors.initials: T
authors.lastname: Blumenthal-Katzir
authors.affiliation: Hypertension Research Unit, Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Israel.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hollander
authors.affiliation: Department of Neurology, Laboratory of Experimental Neurology and Neuroimmunology, AHEPA University Hospital, University of Thessaloniki, Macedonia, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Grigoriadis
authors.affiliation: Department of Neurology, Laboratory of Experimental Neurology and Neuroimmunology, AHEPA University Hospital, University of Thessaloniki, Macedonia, Greece.
authors.forename: Olga
authors.initials: O
authors.lastname: Touloumi
authors.affiliation: Department of Neurology, Laboratory of Experimental Neurology and Neuroimmunology, AHEPA University Hospital, University of Thessaloniki, Macedonia, Greece.
authors.forename: Roza
authors.initials: R
authors.lastname: Lagoudakic
authors.affiliation: Hypertension Research Unit, Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Israel. Electronic address: rtalma@post.tau.ac.il.
authors.forename: Talma
authors.initials: T
authors.lastname: Rosenthal
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D006973:Hypertension / Q000150:complications / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D018782:Maze Learning / Q000187:drug effects; D055442:Metabolome / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects; D000077333:Telmisartan
chemical_list: D001562:Benzimidazoles; D001565:Benzoates; D001786:Blood Glucose; D000077333:Telmisartan
keywords: Brain MRI; CRDH; Diabetes; Hypertension; Telmisartan