Author: Milan Radojicic MD

Cells of the ependymal region are vestiges of neuroepithelial cells that give rise to neurons and glia during mammalian development [1] and are known to orchestrate the regenerative response in tailed amphibians [2]. Ependymal region cells have been shown to proliferate [1, 3-5] and migrate [6-8] following spinal cord injury. This finding has led some authors to speculate on their role in endogenous repair in humans [9]. Indeed, the kinetics of ependymal region cell proliferation and differentiation have been correlated with the recovery of lower limb motor function in rats following contusion injuries [5]. Of note, neural stem cells have been isolated from the CNS [6, 10, 11], including regions near the central canal [12]. Unlike the SVZ, the prototypical stem cell niche of the CNS (for a review, see [13]), multipotent cells of the ependymal region in the spinal cord appear restricted to glial lineages [5, 6, 8]. Gliogenesis near the central canal includes the generation of ependymal cells [3], reactive astrocytes [5, 6, 8], oligodendrocyte precursors [14] and microglia [15]. Glia are supportive cells of the CNS and are critical for maintaining the structural and functional integrity of the spinal cord after injury [16]. Even reactive astrocytes, long thought to be inhibitory to axonal regeneration, appear to play a role in repair of SCI lesions [5, 17, 18]. Therefore, it stands to reason that disruption of the ependymal stromal epithelium, along with periependymal stem/progenitor cells, may represent a heretofore unrecognized pathogenic mechanism in spinal cord injury, which would hinder gliogenesis in the ependymal region and subsequently wound repair in the spinal cord (and brain). Indeed, the progressive disruption of this cell layer, through mechanical and cytotoxic means, could represent a disease mechanism that tips the balance between injury and repair in the spinal cord (and brain) toward further cytoarchitectural destruction of lesions over time. Moreover, I suggest this conceptualized disease process should be investigated in other multipotent niches (e.g., in the brain, blood vessels and other organs and systems) as a basis for understanding related degenerative disorders and sequelae.

The dictum is simple: Repair the ependyma and you will repair the brain and spinal cord.