Impact of free GSNO on MAP, (panel A), HR, (panel B) and PAP (panel C).

<p>p_interaction, p_dose and p_time < 10⁻⁴ for all parameters (two-way ANOVA; post-hoc Bonferroni test). Each animal (n = 7) received all the treatments. Arrows indicate for each dose the time span where significant differences <i>vs</i>. PBS were observed. Grey boxes represent the duration of anesthesia and red vertical dashed lines the time of injection.</p

Detailed impact of formulated GSNO at 7.5 mg/kg on MAP (panel A), HR (panel B) and PAP (panel C) within the first half day following administration.

<p>Each animal (n = 7) received all the treatments (Implants: 7.4 ± 0.2; Microparticles: 7.7 ± 0.2 mg/kg).</p

<i>In vitro</i> releases of GSNO from <i>in situ</i> forming implants and microparticles.

<p>GSNO loadings were 1.25% or 5% m/m (corresponding respectively to 7.5 mg/kg and 30 mg/kg of GSNO for <i>in vivo</i> experiments) based on the amount of polymer/GSNO/solvent solution. Panel A represents the release of GSNO expressed as % of the initial load; Panel B represents the release of GSNO in absolute values. Values are mean ± s.e.m. (n = 3).</p

Impact of the treatments on whole blood platelet aggregation (aggregometry AUC).

<p>Treatments were: PBS (n = 6), empty microparticles (n = 8), free GSNO at 7.5mg/k g(n = 5) or 30 mg/kg (n = 5), <i>in situ</i> implants loaded with 7.5 ± 0.8 mg/kg (n = 7) or 32.1 ± 4.3 mg/kg (n = 10) of GSNO and <i>in situ</i> microparticles loaded with 7.9 ± 0.6 mg/kg (n = 7) or 31.4 ± 3.6 mg/kg (n = 10) of GSNO. The red vertical dashed lines represent the time of injection. †: p < 0.05 <i>vs</i>. 1 h following substance administration within the same group (one-way ANOVA; post-hoc Bonferroni test).</p

Impact of formulated GSNO at 30 mg/kg on MAP (panel A), HR (panel B) and PAP (panel C).

<p>Each animal (n = 7) received all the treatments (Implants: 31.9 ± 0.5; Microparticles 30.9 ± 0.6 mg/kg). Day-night cycles are marked in days (D1, D2 and D3) and nights (N1, N2) periods. For more clarity, after the first hour, only one point for each hour was represented. *: p < 0.05 <i>vs</i>. PBS (one-way ANOVA; post-hoc Bonferroni test).</p

Impact of the treatments on neurological score, infarct size and edema volume.

<p>Treatments were: empty microparticles (n = 8), free GSNO at 7.5 mg/kg (n = 8) and <i>in situ</i> implants loaded at 30.1 ± 1.5 mg/kg (n = 8) or microparticles at 31.4 ± 0.9 mg/kg (n = 6) of GSNO, injected in male Wistar rats 2 h after thromboembolic stroke induction. Neurological score (panel A, maximal score 160) was measured 24 and 48 h after stroke induction, infarct size (panel B) and edema volume (panel C) 48 h after. *: p < 0.05 <i>vs</i>. empty microparticles; #: p < 0.05 <i>vs</i>. free GSNO at 7.5 mg/kg; <i>ο</i>: p < 0.05 <i>vs</i>. <i>in situ</i> implants (Kruskal-Wallis; post-hoc Mann-Whitney test).</p

Impact of formulated GSNO at 7.5 mg/kg on MAP (panel A), HR (panel B) and PAP (panel C).

<p>Each animal (n = 7) received all the treatments (Implants: 7.4 ± 0.2; Microparticles: 7.7 ± 0.2 mg/kg). Day-night cycles are marked in days (D1, D2 and D3) and nights (N1, N2) periods. For more clarity, after the first hour, only one point for each hour was represented. *: p < 0.05 <i>vs</i>. PBS (one-way ANOVA; post-hoc Bonferroni test).</p

Detailed impact of formulated GSNO at 30 mg/kg on MAP (panel A), HR (panel B) and PAP (panel C) within the first half day following administration.

<p>Each animal (n = 7) received all the treatments (Implants: 31.9 ± 0.5; Microparticles 30.9 ± 0.6 mg/kg).</p