FTY720 Preserves Blood-Brain Barrier Integrity Following Subarachnoid Hemorrhage in Rats

Would this be a possible solution to  Inflammatory action leaking through the blood brain barrier. in the neuronal cascade of death? More research needed that will never occur.

1. Abdullah Muhammad₂,₃,
2. Jennifer Harris₁,
3. Benjarat Changyaleket₂,₃,
4. Dale Pelligrino₂,₃,
5. Hao-liang Xu₂,₃ and
6. Fernando Testai₂,₃

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1. Published online before print April 8, 2015, 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.