Rapid, widespread, and longlasting induction of nestin contributes to the generation of glial scar tissue after CNS injury.

TLDR

Neuronal regeneration does not generally occur in the central nervous system after injury, a failure attributed to the formation of glial scar tissue. The study explores whether the spatiotemporal pattern of nestin expression reflects a population of nestin‑positive cells that proliferate and migrate from near the central canal to the lesion site in response to injury. After CNS injury, nestin is rapidly induced in reactive astrocytes and cells near the central canal within 48 hours, persists for at least 13 months, and its dynamic spatiotemporal pattern—also observed in optic nerve injury and reproduced in nestin promoter/lacZ transgenic mice—suggests that defined regulatory regions mediate this response.

Abstract

Neuronal regeneration does generally not occur in the central nervous system (CNS) after injury, which has been attributed to the generation of glial scar tissue. In this report we show that the composition of the glial scar after traumatic CNS injury in rat and mouse is more complex than previously assumed: expression of the intermediate filament nestin is induced in reactive astrocytes. Nestin induction occurs within 48 hours in the spinal cord both at the site of lesion and in degenerating tracts and lasts for at least 13 months. Nestin expression is induced with similar kinetics in the crushed optic nerve. In addition to the expression in reactive astrocytes, we also observed nestin induction within 48 hours after injury in cells close to the central canal in the spinal cord, while nestin expressing cells at later timepoints were found progressively further out from the central canal. This dynamic pattern of nestin induction after injury was mimicked by lacZ expressing cells in nestin promoter/lacZ transgenic mice, suggesting that defined nestin regulatory regions mediate the injury response. We discuss the possibility that the spatiotemporal pattern of nestin expression reflects a population of nestin positive cells, which proliferates and migrates from a region close to the central canal to the site of lesion in response to injury.