Glial scar and neuroregeneration: histological, functional, and magnetic resonance imaging analysis in chronic spinal cord injury

Abstract

<jats:sec> <jats:title>Object</jats:title> <jats:p>A glial scar is thought to be responsible for halting neuroregeneration following spinal cord injury (SCI). However, little quantitative evidence has been provided to show the relationship of a glial scar and axonal regrowth after injury.</jats:p></jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>In this study performed in rats and dogs, a traumatic SCI model was made using a weight-drop injury device, and tissue sections were stained with H &amp; E for immunohistochemical analysis. The function and behavior of model animals were tested using electrophysiological recording and the Basso-Beattie-Bresnahan Locomotor Rating Scale, respectively. The cavity in the spinal cord after SCI in dogs was observed using MR imaging.</jats:p></jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>The morphological results showed that the formation of an astroglial scar was defined at 4 weeks after SCI. While regenerative axons reached the vicinity of the lesion site, the glial scar blocked the extension of regrown axons. In agreement with these findings, the electrophysiological, behavioral, and in vivo MR imaging tests showed that functional recovery reached a plateau at 4 weeks after SCI. The thickness of the glial scars in the injured rat spinal cords was also measured. The mean thickness of the glial scar rostral and caudal to the lesion cavity was 107.00 ± 20.12 μm; laterally it was 69.92 ± 15.12 μm.</jats:p></jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>These results provide comprehensive evidence indicating that the formation of a glial scar inhibits axonal regeneration at 4 weeks after SCI. This study reveals a critical time window of postinjury recovery and a detailed spatial orientation of glial scar, which would provide an important basis for the development of therapeutic strategy for glial scar ablation.</jats:p></jats:sec>

Spinal cord injury models: a review

“…5 Weight-drop methods in the pig and dog that rely on similar principles as the MASCIS devices have recently been described. 9,10 The MASCIS impactor is widely used and produces a validated and reproducible contusion injury in rat models. However, variability due to bouncing of the impactor rod on the spinal cord after initial drop 'weight bounce' , resulting in multiple impacts, has been of concern.…”

Fgf-Dependent Glial Cell Bridges Facilitate Spinal Cord Regeneration in Zebrafish

“…A significant barrier to mammalian axonal regeneration during SCI is the aggressive astrocytic gliosis that is invariably initiated at the injury site and results in glial scar formation (Stichel and Müller, 1998;Silver and Miller, 2004;Hu et al, 2010). Reactive astrocytes seal the wound, repair the blood-brain barrier and consequently prevent an intense inflammatory response occurring at the injury (Faulkner et al, 2004).…”

The glial scar in spinal cord injury and repair

“…it is noteworthy that the glial scar has a spatial orientation. Magnetic resonance imaging has revealed that the mean thickness of the glial scar rostral/ caudal to the cavity is thicker than that in the region lateral to the cavity formed in rat spinal cord [9] .Another important feature of the glial scar is the increased expression of ECM components, which are predominantly secreted by reactive astrocytes. Among the ECM components, the CSPGs and the nature of their inhibition of axonal regeneration and restriction of plasticity have been studied extensively [10][11][12] .…”

“…it is noteworthy that the glial scar has a spatial orientation. Magnetic resonance imaging has revealed that the mean thickness of the glial scar rostral/ caudal to the cavity is thicker than that in the region lateral to the cavity formed in rat spinal cord [9] .…”