RAPID, WIDESPREAD, AND LONG-LASTING INDUCTION OF NESTIN CONTRIBUTES TO THE GENERATION OF GLIAL SCAR TISSUE AFTER CNS INJURY

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 com plex than previously assumed: expression of the intermediate filament nestin is induced in reactive astrocytes. Nestin induction occurs with in 48 hours in the spinal cord both at the site of lesion and in degen erating 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 indu ction 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 dyn amic pattern of nestin induction after injury was mimicked by lacZ exp ressing cells in nestin promoter/lacZ transgenic mice, suggesting that defined nestin regulatory regions mediate the injury response. We dis cuss the possibility that the spatiotemporal pattern of nestin express ion 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.