Genome-wide gene expression profiling of stress response in a spinal cord clip compression injury model

Abstract

BackgroundThe aneurysm clip impact-compression model of spinal cord injury (SCI) is a standard injury model in animals that closely mimics the primary mechanism of most human injuries: acute impact and persisting compression. Its histo-pathological and behavioural outcomes are extensively similar to human SCI. To understand the distinct molecular events underlying this injury model we analyzed global mRNA abundance changes during the acute, subacute and chronic stages of a moderate to severe injury to the rat spinal cord.ResultsTime-series expression analyses resulted in clustering of the majority of deregulated transcripts into eight statistically significant expression profiles. Systematic application of Gene Ontology (GO) enrichment pathway analysis allowed inference of biological processes participating in SCI pathology. Temporal analysis identified events specific to and common between acute, subacute and chronic time-points. Processes common to all phases of injury include blood coagulation, cellular extravasation, leukocyte cell-cell adhesion, the integrin-mediated signaling pathway, cytokine production and secretion, neutrophil chemotaxis, phagocytosis, response to hypoxia and reactive oxygen species, angiogenesis, apoptosis, inflammatory processes and ossification. Importantly, various elements of adaptive and induced innate immune responses span, not only the acute and subacute phases, but also persist throughout the chronic phase of SCI. Induced innate responses, such as Toll-like receptor signaling, are more active during the acute phase but persist throughout the chronic phase. However, adaptive immune response processes such as B and T cell activation, proliferation, and migration, T cell differentiation, B and T cell receptor-mediated signaling, and B cell- and immunoglobulin-mediated immune response become more significant during the chronic phase.ConclusionsThis analysis showed that, surprisingly, the diverse series of molecular events that occur in the acute and subacute stages persist into the chronic stage of SCI. The strong agreement between our results and previous findings suggest that our analytical approach will be useful in revealing other biological processes and genes contributing to SCI pathology.

Three-dimensional alteration of cervical anterior spinal artery and anterior radicular artery in rat model of chronic spinal cord compression by micro-CT

“…From the long-term observation of 3D images, we found that the vascular density of compression group had no significant different compared with that of the sham group at the 70th day. A few of studies showed that compensatory mechanisms and angiogenesis might exist in chronic compressive spinal cord injury [17,22]. These mechanisms could be useful to explain the alteration of integral vascular network at different time after spinal cord compression.…”

Rats and axolotls share a common molecular signature after spinal cord injury enriched in collagen-1

“…Rat and Axolotl microarray data: Rat T7 spinal clip compression injury (7 days) microarray (14) was obtained from GEO-NCBI (goo.gl/Hz4Gj9). Axolotl mexicanum spinal cord injury microarray (9) data was obtained from the same server (goo.gl/Eoshgn).…”

Toll-like receptors in central nervous system injury and disease: A focus on the spinal cord

“…In rats sustaining a compression SCI, gene expression profiling showed an increase in TLR expression that persisted into the chronic stages, albeit less pronounced than in the acute phase (Chamankhah et al, 2013).…”