DTI analysis of microstructure.

<p>Direction encoded color maps of typical P25 Control, EPO and NaCl pup rat brain at four different image-planes corresponding to the four levels of DTI indices measurements: Splenium, Body, Body and Genu of the corpus callosum. The different ROIs analyzed are overlaid on the Control map: external capsule (EC), internal capsule (IC), corpus callosum (CC) and cortex (Cx).</p

Volumes of cortical injury at P3 and loss at P25.

<p>Upper panel: percentage of cortical loss at P25 as a function of the percentage of injured cortex at P3 for the both groups: EPO and NaCl. A strong correlation independent of the group was found: R² = 0.67; <i>P</i> = 0.0001. Lower panel: percentage of injured cortex (Inj. Cx) at P3 and percentage of cortical loss (% Cort. loss) at P25 for EPO and NaCl groups. There were no statistical differences between EPO and NaCl groups in terms of cortical injury at P3 and loss at P25. Data are presented as mean ± SD, n = 8 rats for each group, NaCl, EPO and Control.</p

T₂ weighted MRI at P3 and P25.

<p>T₂ weighted images of typical EPO and NaCl treated pup rats at 5 h (P3) and 22 d (P25) after injury showing the evolution of the ischemic lesion in the ipsilateral cortex (right). At P3, ischemic lesion appears as hypersignal. At P25, images present a large cortical loss in the ipsilateral cortex and an abnormal development for the both groups. Remaining trace of lesion was observed for the both groups at the bottom of the cortex (arrows).</p

Myelination and neurofilaments in the ipsilateral cortex.

<p>A) Total length of myelinated fibers (µm) of MBP positive stained fibers in the cortex of Control, NaCl and EPO treated rats. B) MBP average fluorescence intensity in the cortex of Control, NaCl and EPO treated rats. C) Total length of neurofilaments (µm) of SMI31 stained fibers in the cortex of Control, NaCl and EPO treated rats. D) SMI31 average fluorescence intensity in the cortex of Control, NaCl and EPO treated rats. All the data are presented as mean ± SD, *: <i>P</i><0.05, NaCl <i>vs.</i> Control and EPO <i>vs.</i> Control, n = 12 rats for each group, NaCl, EPO and Control.</p

Neurochemical profiles.

<p>Metabolite concentrations in the ipsilateral cortex of EPO and NaCl treated rat pups as well as in the control cortex, and summary of observed metabolite changes following HI in the EPO and NaCl treated rats when compared to the control rats. Changes are displayed with specific orientated arrows: “↑”, increase and “↓”, decrease. The number of “*” represents significant level of <i>P</i><0.05, 0.01, 0.001 respectively. Notice that no significant difference was found between EPO and NaCl cortices. All concentrations are presented as mean ± SD in mM/g except the ratios. Abbreviations: Mac, macromolecules; Asc, ascorbate; Asp<b>,</b> aspartate; GPC, Glycero-phosphocholine; PCho, phosphorylcholine; Cr, creatine; PCr, phosphocreatine; GABA, γ-aminobuttyric acid; Glc, glucose; Glu, glutamate; Gln, glutamine, Ins, myo-inositol; Lac, lactate; NAA, N-acetylaspartate; NAAG, N-acetylaspartylglutamate; PE, phosphoethanolamine and Tau, taurine.</p

Microstructure assessment with DTI.

<p>Histogram of diffusivities (Mean: MD, axial: D_//and radial: D_⊥) as well as fractional anisotropy (FA) values ± SD measured in the in the external capsule (EC), internal capsule (IC), corpus callosum (CC) and cortex (Cx) of the EPO, NaCl and Control rats (n = 6 rats for each group, NaCl, EPO and Control, mean values over the four different images planes corresponding to the one of the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0095643#pone-0095643-g006" target="_blank">figure 6</a>; *, ‡, †: <i>P</i><0.05 NaCl vs. Control, EPO vs. Control and EPO vs. NaCl, respectively).</p

Metabolic profile of cortex.

<p>Typical in¹H-NMR spectra at 9.4T in the ipsilateral cortex of one NaCl treated rat pup (right) as well as in the same area of a Control rat cortex with respective metabolite assignments. All spectra (SPECIAL, TE/TR = 2.8/4000 ms, NT = 840) were displayed with Gaussian apodization (gf = 0.11 s) and scaled relative to the concentration of macromolecules. Abbreviations: Mac, macromolecules; Asc, ascorbate; Asp<b>,</b> aspartate; GPC, Glycero-phosphocholine; PCho, phosphorylcholine; Cr, creatine; PCr, phosphocreatine; GABA, γ-aminobuttyric acid; Glc, glucose; Glu, glutamate; Gln, glutamine, Ins, myo-inositol; Lac, lactate; NAA, N-acetylaspartate; NAAG, N-acetylaspartylglutamate; PE, phosphoethanolamine and Tau, taurine.</p