Timeline diagram of the experimental procedures.

<p>Timeline diagram of the experimental procedures.</p

DE leads to a prolongation of the dTT in linear correlation with DE plasma concentrations (Hemoclot™ assay).

<p>A) dTT was measured with the Hemoclot™ assay in anticoagulation-naïve mice (n = 4), mice receiving 3×37.5 mg/kg over a 24 h feeding period (n = 3) and mice receiving 3×75 mg/kg (n = 3). Statistical significance was assessed with one-way ANOVA and Bonferroni correction. B) Calibration of the coagulometer with lyophilized standard DE plasma gives the DE concentration from the dTT values. Statistical significance was assessed with one-way ANOVA and Bonferroni correction. ** p<0.01; *** p<0.001.</p

No difference in HT and neurological outcome under continuous anticoagulation 72 h after 1 h tMCAO.

<p>A) After 72 h of continuous anticoagulation after 1 h tMCAO, HT blood volume in DE 75 mg/kg pretreated mice (n = 6) and in control mice (n = 7) showed no significant difference. Haemoglobin assay was used for HT blood volume measurement. Results are given in µl presented in a box and whiskers plot depicting mean values, extreme values and the 25 to 75 percent interquartile range. B) Neurological function was evaluated on a 14 point scale (mNSS) after 72 h. Mice which died during the observation period were given 14 points as the worst outcome on the mNSS scale. The values of single mice and the medians are depicted in a dot plot. C) The number of surviving mice per group is given besides their mean body weight in gram.</p

Inclusion – exclusion criteria for MCAO experiments.

<p>Inclusion – exclusion criteria for MCAO experiments.</p

DE pretreatment does not lead to symptomatic hemorrhagic transformation after tMCAO.

<p>A) Neurological function after 1 h and 3 h tMCAO was assessed on a 14 point scale (mNSS) directly prior to reperfusion and at B) 24 h. The values of single mice and the medians are depicted in a dot plot. Statistical significance was assessed with a Mann-Whitney Test for two groups and a Kruskal-Wallis-Test with Dunn’s correction for three or more. * p<0.05.</p

Mice pretreated with DE did not show a greater risk of HT after tMCAO than control mice.

<p>The left two bars show HT volume after 1 h MCAO in control mice (n = 5) and DE-pre-treated mice 37,5 mg/kg (n = 6). Shown on the right is the HT volume after 3 h MCAO in control mice (n = 6), DE-pre-treated mice 37,5 mg/kg (n = 5) and DE-pre-treated mice 75 mg/kg (n = 5). Haemoglobin assay was used for HT blood volume measurement and results are given in µl. Results are showed in a box and whiskers plot depicting mean values, extreme values and the 25 to 75 percent interquartile range. Statistical significance was assessed with a one-way ANOVA with Bonferroni correction. No significant differences were detected.</p

Values and hemispheric ratios of R2’ und rCBV for different degrees of perfusion delay in perfusion-disturbed and corresponding normoperfused tissue.

<p>Values and hemispheric ratios of R2’ und rCBV for different degrees of perfusion delay in perfusion-disturbed and corresponding normoperfused tissue.</p

Description of ROI definition in a representative patient.

<p>MR-angiography shows no flow in the right intracranial ICA and MCA. TTP-images were thresholded according to different degrees of perfusion delay and perfusion delay ranges as compared to the contralateral unaffected hemisphere. The threshold >0 seconds represents the entire perfusion-disturbed area in relation to the upper limit of normoperfusion in the unaffected hemisphere. Areas of perfusion delay were manually outlined in order to generate ROIs which were then transferred to the coregistered T2’- and rCBV-maps. In order to quantify T2’ and rCBV in corresponding areas of the unaffected hemisphere, ROIs were mirrored to the contralateral side. MTT-maps were processed accordingly. ToF: time-of-flight; MRA: MR-angiography; MIP: Maximum Intensity Projection; TTP: time-to-peak; sec: seconds; rCBV: relative cerebral blood volume.</p

Values and hemispheric ratios of T2’ and rCBV for different degrees of perfusion delay in perfusion-disturbed and corresponding normoperfused tissue.

<p>Values and hemispheric ratios of T2’ and rCBV for different degrees of perfusion delay in perfusion-disturbed and corresponding normoperfused tissue.</p

Patients are grouped according to discharge diagnosis (“ICD” = International Classification of Diseases).

<p>“n” depicts the number of patients per diagnosis. “n<0.05” displays the number of patients per diagnosis with GFAP values below the lower detection limit of the used immunoassay. The remaining values (those above the lower detection limit) are displayed as individual values in the graph. Individual patients with increased GFAP values are easy to recognize. Mean GFAP values and standard deviation (SD) are also provided for each diagnosis. The diagnoses with the three highest mean GFAP values are labelled in red. * = GFAP value of one sample is missing. ** = Results of the BE FAST study for comparison <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062101#pone.0062101-Foerch2" target="_blank">[4]</a>.</p