PMID- 25524827 OWN - NLM STAT- MEDLINE DCOM- 20151125 LR - 20171116 IS - 1097-4547 (Electronic) IS - 0360-4012 (Linking) VI - 93 IP - 5 DP - 2015 May TI - Different protective and reparative effects of olmesartan in stroke according to time of administration and withdrawal. PG - 806-14 LID - 10.1002/jnr.23532 [doi] AB - Angiotensin type 1 receptor blockers (ARBs) have induced improved functional recovery and reduced infarct volume in experimental animal models of stroke. Clinical data have indicated a positive correlation between prestroke treatment with ARBs and reduced stroke severity and better outcomes; however, the mechanisms of these beneficial effects are not yet well understood. This study compares the protective and possible reparative effects of continuous oral treatment with olmesartan (OLM) with OLM pretreatment and withdrawal after permanent middle cerebral artery occlusion (pMCAO) in rats. Fifty-two Sprague-Dawley rats were randomly assigned to five groups: MCAO(-/OLM) (OLM 10 mg/kg/day for 14 days after infarct), MCAO(OLM/OLM) (OLM 10 mg/kg/day for 7 days before and 14 days after infarct), MCAO(OLM/-) (OLM 10 mg/kg/day for 7 days before infarct), sham, and control. We analyzed functional recovery; lesion size; cell death; expression of the pro-oxidant enzyme NADPH oxidase 4 (NOX-4); isolectin-B4; and repair markers such as glial fibrillary acidic protein, vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor (BDNF). All of the OLM-treated groups showed significantly better functional scores and reduced infarct sizes and cell death compared with the control group 14 days after pMCAO. Levels of NOX-4, VEGF, and BDNF were significantly lower in the brains of the MCAO(OLM/OLM) and sham groups compared with the other groups. OLM treatment improved functional recovery and reduced lesion size and cell death after cerebral ischemia. Only the continuous administration of OLM before and after stroke reduced oxidative stress levels, with better tissue preservation, without triggering brain repair marker activation. CI - (c) 2014 Wiley Periodicals, Inc. FAU - Gutierrez-Fernandez, Maria AU - Gutierrez-Fernandez M AD - Department of Neurology and Stroke Centre, Neuroscience and Cerebrovascular Research Laboratory, La Paz University Hospital, Neuroscience Area of IdiPAZ (Health Research Institute), Autonoma University of Madrid, Madrid, Spain. FAU - Fuentes, Blanca AU - Fuentes B FAU - Rodriguez-Frutos, Berta AU - Rodriguez-Frutos B FAU - Ramos-Cejudo, Jaime AU - Ramos-Cejudo J FAU - Otero-Ortega, Laura AU - Otero-Ortega L FAU - Diez-Tejedor, Exuperio AU - Diez-Tejedor E LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20141218 PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (Angiotensin II Type 1 Receptor Blockers) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Imidazoles) RN - 0 (Tetrazoles) RN - 0 (Vascular Endothelial Growth Factor A) RN - 8W1IQP3U10 (olmesartan) RN - EC 1.6.3.- (NADPH Oxidase 4) RN - EC 1.6.3.- (NADPH Oxidases) RN - EC 1.6.3.- (Nox4 protein, rat) SB - IM MH - Angiotensin II Type 1 Receptor Blockers/*administration & dosage MH - Animals MH - Brain-Derived Neurotrophic Factor/metabolism MH - Disease Models, Animal MH - Double-Blind Method MH - Drug Administration Schedule MH - Female MH - Glial Fibrillary Acidic Protein/metabolism MH - Imidazoles/*administration & dosage MH - In Situ Nick-End Labeling MH - Magnetic Resonance Imaging MH - Male MH - NADPH Oxidase 4 MH - NADPH Oxidases/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Severity of Illness Index MH - Statistics, Nonparametric MH - Stroke/*drug therapy/pathology MH - Tetrazoles/*administration & dosage MH - Time Factors MH - Vascular Endothelial Growth Factor A/metabolism OTO - NOTNLM OT - cerebral infarct OT - olmesartan OT - protective and repair markers EDAT- 2014/12/20 06:00 MHDA- 2015/12/15 06:00 CRDT- 2014/12/20 06:00 PHST- 2014/07/28 00:00 [received] PHST- 2014/11/05 00:00 [revised] PHST- 2014/11/05 00:00 [accepted] PHST- 2014/12/20 06:00 [entrez] PHST- 2014/12/20 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] AID - 10.1002/jnr.23532 [doi] PST - ppublish SO - J Neurosci Res. 2015 May;93(5):806-14. doi: 10.1002/jnr.23532. Epub 2014 Dec 18.