Abstract
BackgroundCentral nervous system axons lack a robust regenerative response following spinal cord injury (SCI) and regeneration is usually abortive. Supraspinal pathways, which are the most commonly studied for their regenerative potential, demonstrate a limited regenerative ability. On the other hand, propriospinal (PS) neurons, with axons intrinsic to the spinal cord, have shown a greater regenerative response than their supraspinal counterparts, but remain relatively understudied in regards to spinal cord injury.ResultsUtilizing laser microdissection, gene-microarray, qRT-PCR, and immunohistochemistry, we focused on the intrinsic post-axotomy response of specifically labelled thoracic propriospinal neurons at periods from 3-days to 1-month following T9 spinal cord injury. We found a strong and early (3-days post injury, p.i) upregulation in the expression of genes involved in the immune/inflammatory response that returned towards normal by 1-week p.i. In addition, several regeneration associated and cell survival/neuroprotective genes were significantly up-regulated at the earliest p.i. period studied. Significant upregulation of several growth factor receptor genes (GFRa1, Ret, Lifr) also occurred only during the initial period examined. The expression of a number of pro-apoptotic genes up-regulated at 3-days p.i. suggest that changes in gene expression after this period may have resulted from analyzing surviving TPS neurons after the cell death of the remainder of the axotomized TPS neuronal population.ConclusionsTaken collectively these data demonstrate that thoracic propriospinal (TPS) neurons mount a very dynamic response following low thoracic axotomy that includes a strong regenerative response, but also results in the cell death of many axotomized TPS neurons in the first week after spinal cord injury. These data also suggest that the immune/inflammatory response may have an important role in mediating the early strong regenerative response, as well as the apoptotic response, since expression of all of three classes of gene are up-regulated only during the initial period examined, 3-days post-SCI. The up-regulation in the expression of genes for several growth factor receptors during the first week post-SCI also suggest that administration of these factors may protect TPS neurons from cell death and maintain a regenerative response, but only if given during the early period after injury.
Highlights
Central nervous system axons lack a robust regenerative response following spinal cord injury (SCI) and regeneration is usually abortive
The supraspinal pathways most often tested after SCI for their regenerative ability, have limited inherent regenerative abilities, even when more permissive environments are established at the injury site [4,5]
Gene-Microarray analysis of the thoracic PS (TPS) intrinsic response to axotomy Hypothesis -free single gene analysis We first initiated a genome wide, hypothesis free analysis to examine the overall response of TPS neurons to axotomy following a low thoracic spinal transection
Summary
Central nervous system axons lack a robust regenerative response following spinal cord injury (SCI) and regeneration is usually abortive. Propriospinal (PS) neurons, with axons intrinsic to the spinal cord, have shown a greater regenerative response than their supraspinal counterparts, but remain relatively understudied in regards to spinal cord injury. In concert with supraspinal nerve tracts, PS neurons play an important role in locomotor function, limb coordination, and postural support [14]. In spite of their importance in spinal motor function, as well as their greater regenerative potential, and potential for postinjury axonal plasticity [15,16], PS neurons have been relatively understudied. We paid particular attention to changes related to their regenerative ability and to early cell loss, based on the hypothesis that the short distance from the lesion would ensure a maximal regenerative response
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