title: Fingolimod (FTY720) Reduces Cortical Infarction and Neurological Deficits During Ischemic Stroke Through Potential Maintenance of Microvascular Patency.
abstract: Fingolimod (FTY720) reduces infarct volume and improves neurological deficits in different rodent stroke models by modulating inflammatory and immune processes. However, studies on FTY720 regarding its non-immunological efficacy on ischemic cerebral tissue are sparse. Here we investigated whether FTY720 has cytoprotective and restorative properties following ischemic stroke in mice. Male mice received FTY720 (1mg/kg) or a vehicle solution intraperitoneally immediately prior to transient middle cerebral artery occlusion (tMCAO; 30 min.) and 48 hours thereafter. Infarct volume was determined on T2-weighted magnetic resonance images on day 1 and 7 after tMCAO. Motor function was assessed by the ladder rung walking test using a foot fault score. Specific immunostainings were performed to quantify neuronal density, astrocytic reactivity, microvascular density and expression of synaptophysin in the cortical perilesional area on consecutive brain slices. The amount of brain-derived neurotrophic factor (BDNF) was examined using ELISA analyses. FTY720 treatment significantly reduced infarct volumes and motor deficits compared to controls. Neuronal survival, astrogliosis as well as synaptogenesis and BDNF expression in the penumbra of the infarcted cortex did not significantly differ between the treatment groups. Taken together, our data support the hypothesis that the key mode of FTY720 action in stroke is the reduction of microvascular thrombosis and not a direct effect at the neurovascular unit (NVU).
authors: Michael K
authors: MK
authors: Schuhmann
authors: Milos
authors: M
authors: Krstic
authors: Christoph Kleinschnitz, MD, University Clinic Essen, Department of Neurology, Hufelandstraße 55, 45147 Essen, Germany. neurologie@uk-essen.de.
authors: Christoph
authors: C
authors: Kleinschnitz
authors: University Hospital Würzburg, Department of Neurology, Josef-Schneider Strasse 11, 97080 Würzburg, Germany. felix.fluri@gmx.ch.
authors: Felix
authors: F
authors: Fluri
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D020520:Brain Infarction / Q000188:drug therapy*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004195:Disease Models, Animal; D000068876:Fingolimod Hydrochloride / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000187:drug effects*; D020521:Stroke / Q000188:drug therapy*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000068876:Fingolimod Hydrochloride