Dorsal view of brains from K173 infected SD rats after systemic lavage.

<p>(<b>A</b>) Healthy brain of a Control (Ctrl) rat. (<b>B</b>) ECM brain shows petechial hemorrhages especially on cerebellum and edema with disappearance of cerebral longitudinal fissure. (<b>C</b>) NoECM brain presents no macroscopic lesion.</p

Biochemical parameters of SD rats infected by K173.

<p>Globally significant differences between ECM, NoECM and control (CTRL) groups were observed for creatinine (p = 0.001) potassium (p<0.001) glycemia (p<0.001), calcium (p = 0.002), albumin (p<0.001) and total CO₂ (p<0.001). The ECM group was significantly different from the CTRL group for creatinine (p = 0.001), glucose (p = 0.037) and total CO₂ (p<0.001), from the NoECM_LP group only for potassium (p = 0.004) and from the NoECM_HP group for albumin (p = 0.001) and chloride (p = 0.0029). To suppress the influence of parameter units, the data are plotted on a standardized scale, e.g. mean = 0 and SD = 1.</p

Localization of parasites in cerebral vessels in ECM K173 infected SD rats.

<p>(<b>A</b>) Thrombosis. (<b>B</b>) Parasites were localized in peripheries of cerebral vessels in direct contact with the endothelium. <b>(C</b> and <b>D)</b> Extravascular hemorrhage with parasites (arrows) localized in peripheries. ECM brains were collected from rats without systemic lavage. Histological slices of ECM brains stained using hematoxylin-eosin.</p

Histological illustrations of cerebral lesions in ECM K173 infected SD rats.

<p>(<b>A</b>) Acute perivascular neuropilar hemorrhage with severe extension (circle). Diffuse intracerebral hemorrhages (<b>B</b> and <b>C</b>) with presence of numerous parasites (<b>D</b>). ECM brains were collected from rats without systemic lavage. Histological slices of ECM brains stained using hematoxylin-eosin.</p

Hematological parameters in the course of infection in ECM (n = 17), NoECM (n = 22) and control (n = 13) groups.

<p>Mean Corpuscular Volume (MCV) (<b>A</b>) and Mean Corpuscular Hemoglobin Concentration (MCHC) (<b>B</b>) kinetics. The hematological parameters are aligned from and on the basis of the day (D) when parasitemia was estimated at 5% (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0181300#pone.0181300.s001" target="_blank">S1B Fig</a>). All data are represented by mean ±standard error of the mean (SEM).</p

White blood cell count during the course of infection in ECM (n = 17), NoECM (n = 22) and control (n = 13) groups.

<p>Parameters are aligned from and on the basis of the day (D) where parasitemia was estimated at 5% (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0181300#pone.0181300.s001" target="_blank">S1B Fig</a>). All data are represented by the mean ± standard error of the mean (SEM).</p

Expression of cytokines in SD rat brains infected by K173.

<p>Cerebral cytokine gene expression was assessed in ECM (n = 14), NoECM (n = 23) and Control brains (n = 7). Samples were collected on day ECM onset for ECM rats, after the parasitemia reached 30% for NoECM rats and for control rats at the same time as ECM and NoECM groups. Box plots represent medians and 25th and 75th percentiles. Among all the cytokines investigated only the gene expression of INFγ (p<0.001), IL10 (p<0.001), IL1β (p = 0.001), TNFα (p = 0.045), MIP1α (p<0.014) and MIP1β (p<0.001) were significantly different between infected and control rats. The symbol * indicates outliers.</p

Edema test.

<p>Quantification of water contained in brains of ECM (n = 12), NoECM (n = 13) and Control brains (n = 8). The brain water content in the ECM group was statistically higher than that in NoECM (p = 0.007) and Control rats (p = 0.02). The p value was not significant (ns) between NoECM and Control rats (p = 0.66). Box plots represent medians and 25^th and 75^th percentiles. Statistical test used: Kruskal-Wallis One Way Analysis of Variance on Ranks and Donn’s Method for all pairwise comparisons. *p<0.05.</p

Hematological parameters in the course of infection in ECM (n = 17), NoECM (n = 22) and control (n = 13) groups.

<p>Platelet counts (<b>A</b>) and Mean Platelet Volume (MPV) (<b>B</b>). The hematological parameters are aligned from and on the basis of the day (<b>D</b>) when parasitemia was estimated at 5% (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0181300#pone.0181300.s001" target="_blank">S1B Fig</a>). All data are represented by the mean ± standard error of the mean.</p

Kaplan-Meyer curve estimate of a survival, with 95% confidence limits, of young Sprague Dawley (SD) rats with Experimental Cerebral Malaria (ECM; n = 18) and without Experimental Cerebral Malaria (NoECM; n = 22) after K173 infection.

<p>The solid lines are the survival curves and the dashed lines are the confidence intervals. Except for 6 rats (3 ECM and 3 NoECM), which cured spontaneously and were sacrificed at day 20, all the infected rats died at the latest on the 17^th day <i>pi</i>. ECM rats died spontaneously between days 5 and 12 while the first cases of fatal outcomes for NoECM rats occurred on day 10. The difference between two groups was significant (p = 0.024).</p