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Neurology April 5, 2016 vol. 86 no. 16 Supplement P5.230
- Abstract
Abstract
Objective:
In this study we investigated the effect of FTY720 in BBB function in the rat model of SAH.
Background:
In a recent study we showed that the
sphingosine-1-phosphate agonist FTY720 reduces neuroinflammation,
preserves pial arteriolar
reactivity, and improves neurological outcome in
rats subjected to subarachnoid hemorrhage (SAH). The immune response
triggered
by SAH leads to blood-brain barrier (BBB)
disruption and brain edema formation which are important determinants of
outcome.
Methods:
SAH was induced in rats via endovascular
perforation of the anterior cerebral artery. Animals were divided into
three groups:
(1) sham control; (2) SAH-vehicle; (3) SAH-FTY720
treated. FTY720 (0.5 mg/kg) was applied intraperitoneally 3h post SAH.
Brain
tissue was collected 48h post SAH. BBB integrity
was evaluated based on parenchymal extravasation of Evan’s blue (EB) and
the expression of endothelial barrier antigen (EBA)
and tight junction proteins (ZO-1 and occludin). Brain edema was
assessed
by measuring the brain water content using the
weight/dry method.
Results:
The parenchymal extravasation of EB in the
SAH-vehicle group was significantly higher than in the sham group
(12.96±3.14 µg/g
tissue, vs. 3.20±2.12 µg/g tissue in the sham
surgical group; p<0.01). The treatment with FTY720 reduced the
extravasation
of EB by almost 50[percnt] (6.96±2.83 µg/g tissue).
Immunohistochemistry staining demonstrated that ZO-1 and occludin,
along
with cerebral microvessels (EBA), held a strong
perivascular expression pattern in the sham-control group. At 48h post
SAH,
the expression of these markers was reduced in the
SAH-vehicle group but largely preserved in the SAH rats treated with
FTY720.
Also, the brain water content was significantly
increased after SAH (SAH: 82.50±0.94[percnt], vs. sham:
79.38±0.37[percnt];
p<0.01), but this was normalized by the
treatment with FTY720 (79.63±0.72 [percnt]).
Conclusions:
These results suggest that the neuroprotective role
of FTY720 extends to the preservation of BBB integrity and attenuation
of cerebral edema following SAH.
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