PMID- 27558201
OWN - NLM
STAT- MEDLINE
DCOM- 20171019
LR  - 20220317
IS  - 1875-5739 (Electronic)
IS  - 1567-2026 (Linking)
VI  - 13
IP  - 4
DP  - 2016
TI  - Fingolimod (FTY720) Reduces Cortical Infarction and Neurological Deficits During 
      Ischemic Stroke Through Potential Maintenance of Microvascular Patency.
PG  - 277-282
AB  - 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).
FAU - Schuhmann, Michael K
AU  - Schuhmann MK
FAU - Krstic, Milos
AU  - Krstic M
FAU - Kleinschnitz, Christoph
AU  - Kleinschnitz C
AD  - Christoph Kleinschnitz, MD, University Clinic Essen, Department of Neurology, 
      Hufelandstrasse 55, 45147 Essen, Germany. neurologie@uk-essen.de.
FAU - Fluri, Felix
AU  - Fluri F
AD  - University Hospital Wurzburg, Department of Neurology, Josef-Schneider Strasse 
      11, 97080 Wurzburg, Germany. felix.fluri@gmx.ch.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United Arab Emirates
TA  - Curr Neurovasc Res
JT  - Current neurovascular research
JID - 101208439
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - G926EC510T (Fingolimod Hydrochloride)
SB  - IM
MH  - Animals
MH  - Brain/metabolism
MH  - Brain Infarction/*drug therapy
MH  - Brain Ischemia/*drug therapy/metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Disease Models, Animal
MH  - Fingolimod Hydrochloride/*pharmacology
MH  - Infarction, Middle Cerebral Artery/*drug therapy/pathology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Microvessels/*drug effects
MH  - Stroke/*drug therapy
EDAT- 2016/10/26 06:00
MHDA- 2017/10/20 06:00
CRDT- 2016/08/26 06:00
PHST- 2016/06/22 00:00 [received]
PHST- 2016/07/13 00:00 [revised]
PHST- 2016/07/15 00:00 [accepted]
PHST- 2016/10/26 06:00 [pubmed]
PHST- 2017/10/20 06:00 [medline]
PHST- 2016/08/26 06:00 [entrez]
AID - CNR-EPUB-77951 [pii]
AID - 10.2174/1567202613666160823152446 [doi]
PST - ppublish
SO  - Curr Neurovasc Res. 2016;13(4):277-282. doi: 10.2174/1567202613666160823152446.