Fig. 1.

Chronic mild hypoxic treatment of preexisting EAE accelerates recovery at the clinical and histopathological levels. (A) The impact of CMH on clinical severity of relapsing–remitting EAE. Once mice developed a clinical score of 2 (arrow), they were randomly assigned to normoxic (control) or CMH conditions, and clinical score was evaluated at daily intervals. All points represent the mean ± SD (n = 26–32 mice per group, cumulative of three separate experiments). Note that compared to normoxic controls, mice treated with CMH showed accelerated clinical recovery, resulting in a marked and sustained reduction in long-term clinical score. (B and C) Frozen sections of lumbar spinal cord taken from disease-free, EAE–normoxia or EAE–CMH mice at the peak and remission phases of disease (14 and 21 d postimmunization, respectively) were stained for the inflammatory leukocyte marker CD45 (AlexaFluor-488) and fluoromyelin-red. (Scale bar, 500 μm [B] and 100 μm [C].) (D and E) Quantification of CD45 (D) and fluoromyelin (E) fluorescent signal at different timepoints. Results are expressed as the mean ± SEM percent area (n = 6 mice per group). Note that following peak disease, CMH markedly suppressed CD45+ leukocyte load within the spinal cord and protected against demyelination. *P < 0.05, **P < 0.01.