Abstract

There exists a trend for a better functional recovery from spinal cord injury (SCI) in younger patients compared to adults, which is also reported for animal studies; however, the reasons for this are yet to be elucidated. The post injury tissue microenvironment is a complex milieu of cells and signals that interact on multiple levels. Inflammation has been shown to play a significant role in this post injury microenvironment. Endogenous neural progenitor cells (NPC), in the ependymal layer of the central canal, have also been shown to respond and migrate to the lesion site. This study used a mild contusion injury model to compare adult (9 week), juvenile (5 week) and infant (P7) Sprague-Dawley rats at 24 h, 1, 2, and 6 weeks post-injury (n = 108). The innate cells of the inflammatory response were examined using counts of ED1/IBA1 labeled cells. This found a decreased inflammatory response in the infants, compared to the adult and juvenile animals, demonstrated by a decreased neutrophil infiltration and macrophage and microglial activation at all 4 time points. Two other prominent cellular contributors to the post-injury microenvironment, the reactive astrocytes, which eventually form the glial scar, and the NPC were quantitated using GFAP and Nestin immunohistochemistry. After SCI in all 3 ages there was an obvious increase in Nestin staining in the ependymal layer, with long basal processes extending into the parenchyma. This was consistent between age groups early post injury then deviated at 2 weeks. The GFAP results also showed stark differences between the mature and infant animals. These results point to significant differences in the inflammatory response between infants and adults that may contribute to the better recovery indicated by other researchers, as well as differences in the overall injury progression and cellular responses. This may have important consequences if we are able to mirror and manipulate this response in patients of all ages; however much greater exploration in this area is required.

Highlights

  • Spinal cord injury (SCI) is a complex and evolving pathology that arises from an insult to the spinal cord; either a mechanical trauma (TSCI) or from a variety of non-traumatic causes

  • This study investigates the temporal response of innate inflammatory cells, reactive astrocytes and neural progenitor cells (NPC) following injury in rats of different maturities to determine where the significant differences lay and how this may translate into the difference in recovery that have been broadly observed

  • There is a trend for better recovery in young animals, as well as in humans following spinal cord injury (SCI) the mechanisms behind these recovery differences remain a mystery

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Summary

Introduction

Spinal cord injury (SCI) is a complex and evolving pathology that arises from an insult to the spinal cord; either a mechanical trauma (TSCI) or from a variety of non-traumatic causes. There are as many manifestations of SCI as there are spinal cord patients; they all share a common basic pathophysiology (Kwon et al, 2004; Profyris et al, 2004; Rowland et al, 2008) This pathology is characterized by cell death and inflammation (Kwon et al, 2004; Norenberg et al, 2004), myelopathy, breach of the blood-brain barrier, and damage to both the glia and neural fiber tracts (Ronaghi et al, 2010). It has been noted that the profile of the secondary damage phase could vary in an age-dependant manner (Yuan et al, 2013)

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