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Efficacy of high-dose and low-dose simvastatin on vascular oxidative stress and neurological outcomes in patient with acute ischemic stroke

Neurological Science, Tokyo, Japan;
Japanese Red Cross Musashino
Hospital, Department of Neurology, Tokyo, Japan;
Tokyo Medical and
Dental University, Department of Endovascular Surgery, Tokyo, Japan
Background: In acute ischemic stroke, enhanced collateral circulation
via the leptomeningeal arteries leads to decreased infarction volume and
better neurological outcome. We previously reported that sphingosine-
1-phosphate receptor 1 (S1PR1) on endothelial cell sensed shear stress
caused by cerebral hypoperfusion and enhanced collateral growth.
Objective: We evaluted S1PR1 expression and the effect of S1PR1
agonist on collateral growth and neurological function after acute
stroke, to seek the therapeutic possibility of S1PR1 modulation.
Patients and Methods / Material and Methods: BALB/c mice
(n=42) underwent left middle cerebral artery occlusion (MCAO).
Ischemic cortices were quantied for S1PR1 mRNA and immuno-
histochemically analyzed at 6, 24, 48 hours after surgery. SEW2871
(S1PR1-selective agonist) or vehicle were intraperitoneally injected after
the surgery for 7 days. Neurological functions, leptomeningeal arteries
labeled with ink, and infarction volume were analyzed 7 days later.
Results: S1PR1 mRNA expression was signicantly increased peaking
at 24 hours after MCAO (18 ± 7.6 times, p b0.05) compared to
control. Immunohistochemical analysis showed S1PR1 expression
especially in neurons and endothelial cells of leptomeningeal arteries
in ischemic cortex. The leptomeningeal arteries from anterior
cerebral arteries was signicantly longer in SEW2871-treated mice
compared to control (2.49 ± 0.06 mm versus 1.92 ± 0.02 mm,
pb0.001). Infarction volume was reduced in SEW2871-treated mice
(0.12 ± 0.01 mm
versus 0.33 ± 0.02 mm
,pb0.001). Neurological
decit score (0 to 4, with 4 being most severe) improved in
SEW2871-treated mice (0.25 ±0.25 versus 1.33 ± 0.33, p b0.04).
Conclusion: S1PR1-selective agonist has a possibility to improve
neurological outcome, through increasing the collateral growth in
acute ischemic stroke.
Efcacy of high-dose and low-dose simvastatin on vascular
oxidative stress and neurological outcomes in patient with acute
ischemic stroke
S. Muengtaweepongsa, N. Uransilp, P. Chaiyawatthanananthn.
Thammasat University, Medicine, Pathumthani, Thailand
Background: Stroke is the leading cause of death and long term
disability. Ones cause of acute ischemic stroke (AIS) is rupture of
atherosclerotic plaques. Soluble LOX-1 (sLOX-1) and NO are used as
biomarkers for vascular oxidative stress that can reect to stabiliza-
tion of atherosclerotic plaque. Previous study showed that simva-
statin can reduce oxidative stress and LOX-1 expression.
Objective: We aim to investigate outcomes of simvastatin 10 mg/day
and 40 mg/day on vascular oxidative stress and neurological
outcomes in patients with acute ischemic stroke.
Patients and Methods / Material and Methods: 65 patients with AIS
within 24 hour-stroke symptom onset were randomized to treat with
simvastatin 10 mg/day or 40 mg/day for 90 days. Personal data and past
history of all patients were recorded at baseline. The blood chemistries
were measured by standard laboratory techniques. Serum sLOX-1 and
NO levels, and neurological outcomes including NIHSS, mRS and Bathel
index were tested at baseline and Day 90 after simvastatin therapy.
Results: Baseline characteristics were not signicantly different in
both groups except history of hypertension. Serum sLOX-1 and NO
levels signicantly reduce in both groups (sLOX-1 = 1.19±0.47 and
0.98±0.37 ng/ml; NO = 49.28± 7.21 and 46.59 ± 9.36 μmol/l) in 10
mg/day and 40 mg/day simvastatin groups, respectively. Neurolog-
ical outcomes including NIHSS, mRS and Bathel index, signicantly
improve in both groups. However, no different in NO level and
neurological outcomes at 90 day in both group.
Conclusion: Simvastatin might reduce serum sLOX-1 and NO levels.
But no difference in clinical outcomes was found between high and
low dose simvastatin.
Blood based protein biomarkers to distinguish ischemic from
hemorrhagic stroke: A systematic review
S. Misra
, A. Kumar
, P. Kumar
, A.K. Yadav
, D. Mohania
, R. Sagar
D. Vibha
, K. Prasad
All India institute of Medical sciences,
Department of Neurology, New Delhi, India;
All India institute of
Medical sciences, Dr. RP Centre, New Delhi, India
Background: Computed Tomography (CT) scan is the mainstay for
distinguishing ischemic from hemorrhagic stroke; but the facility of
CT scan is not easily available. A blood based biomarker approach
may be required to distinguish ischemic stroke (IS) from hemor-
rhagic stroke (HS) in pre-hospital settings.
Objective: To conduct a systematic review of studies of blood based
protein biomarkers for distinguishing IS from HS.
Patients and Methods / Material and Methods: A comprehensive
literature search was carried out till March 07, 2017 in PubMed,
Cochrane, Medline, OVID, and Google Scholar databases. Methodo-
logical quality of each study was assessed using the modied Quality
Assessment of Diagnostic Accuracy Studies questionnaire.
Results: Eighteen studies were identied relevant to our systematic
review. Ten single biomarkers and seven panels of different biomarkers
were identied which showed potential for differentiating IS and HS.
Activated Protein C- Protein C Inhibitor Complex (APC-PCI) (sensitivity-
96%), Glial Fibrillary Acidic Protein (GFAP) (specicity-100%) and a
panel of APC-PCI & GFAP (sensitivity- 71%) and Retinol Binding Protein
4 (RBP4) & GFAP (specicity- 100%) were found to have high sensitivity
and specicity for differentiating the two stroke types.
Conclusion: Our systematic review does not recommend the use of any
blood biomarker for clinical purposes yet based on the studies conducted
till date. However, GFAP has been replicated several times and has shown
high sensitivity and specicity for differentiating ICH from IS; adequately
powered diagnostic studies conducted in systematic phases are required
to afrm its role as a differentiating blood biomarker in stroke.
Endothelial cell sampling coupled with transcriptomic analysis in
a swine model of mechanical thrombectomy
N. Jaff
, R. Grankvist
, L. Muhl
, A. Chireh
, M. Sandell
, S. Jonsson
, S. Holmin
Karolinska Institutet, Clinical Neuroscience,
Stockholm, Sweden;
Karolinska Institutet, Medical Biochemistry and
Biophysics, Stockholm, Sweden;
Royal Institute of Technology, Materials
Science, Stockholm, Sweden
Abstracts / Journal of the Neurological Sciences 381 (2017) 54180106
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