TY  - JOUR
A1  - Brunkhorst, Robert
A1  - Kanaan, Nathalie
A1  - Koch, Alexander
A1  - Ferreirós Bouzas, Nerea
A1  - Mirceska, Ana
A1  - Zeiner, Pia Susan
A1  - Mittelbronn, Michel Guy André
A1  - Derouiche, Amin
A1  - Steinmetz, Helmuth
A1  - Förch, Christian
A1  - Pfeilschifter, Josef
A1  - Pfeilschifter, Waltraud
T1  - FTY720 treatment in the convalescence period improves functional recovery and reduces reactive astrogliosis in photothrombotic stroke
T2  - PLoS One
N2  - Background: The Sphingosine-1-phosphate (S1P) signaling pathway is known to influence pathophysiological processes within the brain and the synthetic S1P analog FTY720 has been shown to provide neuroprotection in experimental models of acute stroke. However, the effects of a manipulation of S1P signaling at later time points after experimental stroke have not yet been investigated. We examined whether a relatively late initiation of a FTY720 treatment has a positive effect on long-term neurological outcome with a focus on reactive astrogliosis, synapses and neurotrophic factors.
Methods: We induced photothrombotic stroke (PT) in adult C57BL/6J mice and allowed them to recover for three days. Starting on post-stroke day 3, mice were treated with FTY720 (1 mg/kg b.i.d.) for 5 days. Behavioral outcome was observed until day 31 after photothrombosis and periinfarct cortical tissue was analyzed using tandem mass-spectrometry, TaqMan®analysis and immunofluorescence.
Results: FTY720 treatment results in a significantly better functional outcome persisting up to day 31 after PT. This is accompanied by a significant decrease in reactive astrogliosis and larger post-synaptic densities as well as changes in the expression of vascular endothelial growth factor α (VEGF α). Within the periinfarct cortex, S1P is significantly increased compared to healthy brain tissue.
Conclusion: Besides its known neuroprotective effects in the acute phase of experimental stroke, the initiation of FTY720 treatment in the convalescence period has a positive impact on long-term functional outcome, probably mediated through reduced astrogliosis, a modulation in synaptic morphology and an increased expression of neurotrophic factors.
Y1  - 2013
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/31140
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-311402
SN  - 1932-6203
N1  - Copyright: © 2013 Brunkhorst et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 8
IS  - (7):e70124
PB  - PLoS
CY  - Lawrence, Kan.
ER  -