Additionally, a study investigating the early and late phase of progressive demyelination in the transgenic TNF�Coverexpressing mouse strain Tg6074 fulfilled the criteria. While the early disease stage Gentamycin Sulfate included mice up to three weeks of age the late stage comprised mice with an age of three to nine weeks. The present re-analysis of publically available data sets of MS, EAE, TMEV-IDD, and TNFtg generally displayed a lower number of DEGs as compared to the original studies. This might be attributed to the highly stringent filtering criteria suggested to be essential for high reproducibility across studies and platforms. However, at the level of the most severely affected biological modules, the current results are in general agreement with the original studies. Meta-analyses of microarray experiments can be broadly divided into analyses combining statistical significance across studies 1.) on the gene level, including list comparisons, and 2.) on the pathway level, including cross-study GSEA. In the present analysis, the list comparison method did only retrieve 12 DEGs that were commonly affected in MS, EAE, TMEV-IDD, and TNFtg, supporting previous studies suggesting that list comparisons are 
an over-conservative approach. Notably, 8 out of these 12 common DEGs are known to be expressed by macrophages. Interestingly, all of the 12 DEGs in the intersection were down-regulated in MS, while they were upregulated in the animal models. The reason for this disconcordance remains unclear. However, this observation is in agreement with the recently reported poor transcriptional overlap of mouse models and human inflammatory diseases. The observation of a cluster of 6 GO terms comprising 47 genes involved in coagulation and hemostasis supports the results of a proteomic analysis of MS. Concordantly, the thrombin inhibitor hirudin leads to a dramatic improvement in disease severity in EAE. Furthermore, fibrinogen depletion leads to an increased lifespan, retardation of the clinical symptoms and delayed inflammation and demyelination in TNFtg. The importance of the coagulation cascade in disease development has also been shown in a treatment study with batroxobin, a thrombin-like defibrinogenating enzyme, in TMEV-IDD, which resulted in decreased clinical signs and reduced CNS demyelination in treated animals. Based on the detailed histological and immunohistological descriptions of Lucchinetti et al., we assumed that demyelinating conditions analogous to all four MS patterns should be associated by a transcriptional up-regulation of genes comprised by the GO term “T cell mediated immunity”. Accordingly, a moderate percentage of DEGs associated with this gene signature was Danshensu detected in EAE, TMEV-IDD, and TNFtg. This transcriptional change reflects the histological demonstration of inflammatory T cells and macrophages within the lesions in MOG-induced EAE, TMEV-IDD, and TNFtg as shown in previous studies. Conditions analogous to MS pattern II were anticipated to be accompanied by an additional upregulation of genes comprised by the GO term “immunoglobulin mediated immune response”. This GO term comprises genes involved in the synthesis of immunoglobulins as well as complement factors and therefore includes both important features indicative of MS pattern II. Accordingly, we observed a high percentage of DEGs associated to this gene signature in EAE and TMEV-IDD, and a significantly lower percentage in TNFtg. This result supports the hypothesis that a type II autoimmunity analogous to pattern II of MS is an important pathogenic feature of TMEV-IDD and certain subtypes of EAE.