Gene expression analysis of normal appearing brain tissue in an animal model for multiple sclerosis revealed grey matter alterations, but only minor white matter changes

Cyclooxygenase expression and prostaglandin levels in central nervous system tissues during the course of chronic relapsing experimental autoimmune encephalomyelitis (EAE)

“…The snap-frozen cerebral cortex, cerebellum and spinal cord from each of five mice per treatment were pulverised, suspended in 15% (v/v) ethanol and centrifuged to generate supernatants which were applied to C-18 Sep-Pak separation columns followed by measurement of PGE 2 and PGD 2 using commercial enzyme immunoassay kits. *p \ 0.05 and **p \ 0.01 compared to normal values using ANOVA with Dunnett's post-hoc test and cerebellum, which may account for the lack of change in PG levels during the acute phase of CR EAE [9,11,38]. However, the primary stage of CR EAE is typified by pathological alterations throughout the spinal cord that are closely associated with dense parenchymal inflammatory cell infiltration [58][59][60].…”

“…The disease is also typified by inflammatory changes including the presence of cellular lesions, which occur predominately in the spinal cord, to a lesser extent in the cerebellum and rarely in the cerebral cortex [9,11,38]. Therefore, the preferential distribution of inflammation in the CNS may be reflected in the levels of mediators, including COX isoenzymes and prostanoids, which are present and may influence the relapsing-remitting course of the disease.…”

Current and Future Applications of Transcriptomics for Discovery in CNS Disease and Injury

“…Microarray analysis of normal-appearing grey matter in the cortex of EAE-affected rats identified numerous DE genes, particularly downregulation of genes encoding mitochondrial proteins; this may be a result of neurodegeneration in the spinal cord [54] . Transcriptional changes in normal-appearing white matter have been demonstrated in the post-mortem brains of human MS patients [ 55, 56 ; see Human Studies of Neural Disease and Injury, pp 320]; however, this finding was not recapitulated in an EAE study [54] , illustrating the differences that may be seen between human MS and its animal models.…”

“…Microarray analysis findings suggest that both normal-appearing white and grey matter from affected animals or subjects may, in fact, have altered gene expression compared to normal control tissue, indicating a system-wide effect [54,56,135] . Additionally gene expression changes are comparable between rats given a mild contusion injury and those given a laminectomy only, emphasising the importance of including appropriate sham-operated controls rather than naïve animals in microarray studies of neurotrauma [96] .…”

“…Transcriptomics has identified gene expression changes in cortical grey matter distant from lesions that appeared histologically normal [54] . Microarray analysis of normal-appearing grey matter in the cortex of EAE-affected rats identified numerous DE genes, particularly downregulation of genes encoding mitochondrial proteins; this may be a result of neurodegeneration in the spinal cord [54] .…”