Title:Fingolimod (FTY720) Reduces Cortical Infarction and Neurological Deficits During Ischemic Stroke Through Potential Maintenance of Microvascular Patency
Volume: 13
Issue: 4
Author(s): Michael K. Schuhmann, Milos Krstic, Christoph Kleinschnitz and Felix Fluri
Affiliation:
Keywords:
tMCAO, experimental stroke, FTY720, non-immunological effects, neurovascular unit.
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).
