Within the lesions of MOG-induced EAE and TMEV-IDD. The pathogenic role of immunoglobulins in EAE remains controversial. However, several types of EAE in mice, rats, and monkeys are accompanied by B cell responses and immunoglobulin deposition. In detail, deposition of immunoglobulin has been described in MOG-induced EAE in Dark Agouti rats, one of the models used in the present meta-analysis. However, studies in B cell deficient mice have shown that B cells are not critical for the development of MOG-induced murine EAE. Experimental models with a marked oligodendrocyte dystrophy such as cuprizone-induced toxicity analogous to the MS patterns III and IV are characterized by an early-onset and marked down-regulation of genes involved in myelination. The magnitude of the transcriptional change roughly parallels the degree of demyelination, which is estimated to affect slightly more than one half of the spinal cord in MOGinduced EAE in female Dark Agouti rats. Similarly, in TMEV-IDD a down-regulation of PLP and MBP mRNA to approximately 58% of control levels has been described using insitu hybridization, and a down-regulation of MBP mRNA to approximately 70% of control levels has been described using RTqPCR. Based on the abundant apoptotic oligodendroglial cell death in pattern III, and non-apoptotic 
oligodendroglial cell death in pattern IV a respective differential expression of the genes of the GO term “positive regulation of apoptotic process” was suggested to differentiate between analogous conditions. Although the TNFtg model is reported to display primary oligodendrocyte apoptosis with subsequent myelin loss as the predominant pathological feature, we were unable to detect (R)-(-)-Modafinic acid corresponding transcriptional changes in the genes comprised by the selected GO terms. The 3,4,5-Trimethoxyphenylacetic acid reason for this lack of concordance remains unclear. The only GO term observed in our re-analysis of this model which is possibly linked to programmed cell death was “ion homeostasis”. It is known that TNF potently increases intracellular Ca2+ and may thereby induce apoptosis. Similar to our results, the original study describing the TNFtg data set also lacks the description of transcriptional changes associated with myelination and apoptosis. It cannot be excluded that previous studies may have overestimated the relative contribution of oligodendrocyte apoptosis in comparison to the pro-inflammatory effects of TNF-overexpression in the pathogenesis of the TNFtg model. Alternatively, it seems plausible that the induction of apoptosis in oligodendrocytes via the p55TNF receptor-signaling pathway may simply occur by activation of the preformed apoptotic cascade without any related transcriptional changes. Further studies are needed to unravel, whether alternate gene signatures are better suited or if transcriptional profiling is generally a poor approach to reflect the degree of demyelination and apoptosis. The up-regulation of apoptosis�Crelated genes in EAE is suggested to be linked to the marked infiltration of T cells, which are known for their marked expression of extrinsic apoptosis pathway genes like Fas and Fas-L. Apoptosis is known to mainly occur in lymphocytes and not in oligodendrocytes in EAE. The contribution of virus-induced oligodendrocyte apoptosis during the pathogenesis of TMEV-IDD is debated controversially, but generally regarded to be low for the TMEV BeAn-strain used in this study. Conclusively, based on the provided results, MOG- and PLP-induced EAE as well as TMEV-IDD are suggested to mimic especially MS pattern II. In contrast, the TNFtg model displayed transcriptional changes anticipated to occur in MS pattern I. The achievable level of novel information in a meta-analysis strongly depends on the availability and quality of raw data.