Central canal ependymal cells proliferate extensively in response to traumatic spinal cord injury but not demyelinating lesions.
The adult mammalian spinal cord has limited regenerative capacity in settings such as spinal cord injury (SCI) and multiple sclerosis (MS). Recent studies have revealed that ependymal cells lining the central canal possess latent neural stem cell potential, undergoing proliferation and multi-lineage differentiation following experimental SCI. To determine whether reactive ependymal cells are a realistic endogenous cell population to target in order to promote spinal cord repair, we assessed the spatiotemporal dynamics of ependymal cell proliferation for up to 35 days in three models of spinal pathologies: contusion SCI using the Infinite Horizon impactor, focal demyelination by intraspinal injection of lysophosphatidylcholine (LPC), and autoimmune-mediated multi-focal demyelination using the active experimental autoimmune encephalomyelitis (EAE) model of MS. Contusion SCI at the T9-10 thoracic level stimulated a robust, long-lasting and long-distance wave of ependymal proliferation that peaked at 3 days in the lesion segment, 14 days in the rostral segment, and was still detectable at the cervical level, where it peaked at 21 days. This proliferative wave was suppressed distal to the contusion. Unlike SCI, neither chemical- nor autoimmune-mediated demyelination triggered ependymal cell proliferation at any time point, despite the occurrence of demyelination (LPC and EAE), remyelination (LPC) and significant locomotor defects (EAE). Thus, traumatic SCI induces widespread and enduring activation of reactive ependymal cells, identifying them as a robust cell population to target for therapeutic manipulation after contusion; conversely, neither demyelination, remyelination nor autoimmunity appears sufficient to trigger proliferation of quiescent ependymal cells in models of MS-like demyelinating diseases.
Centre de recherche du Centre hospitalier universitaire (CHU) de Québec - CHUL et Département de médicine moléculaire, Faculté de médecine, Université Laval, Québec, Canada.
Steve
S
Lacroix
Department of Neurosciences, Faculty of Medicine, Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), and Groupe de recherche sur le système nerveux central (GRSNC), Université de Montréal, Quebec, Canada.
Laura K
LK
Hamilton
Department of Neurosciences, Faculty of Medicine, Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), and Groupe de recherche sur le système nerveux central (GRSNC), Université de Montréal, Quebec, Canada.
Alexandre
A
Vaugeois
Department of Neurosciences, Faculty of Medicine, Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), and Groupe de recherche sur le système nerveux central (GRSNC), Université de Montréal, Quebec, Canada.
Stéfanny
S
Beaudoin
Department of Neurosciences, Faculty of Medicine, Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), and Groupe de recherche sur le système nerveux central (GRSNC), Université de Montréal, Quebec, Canada.
Christian
C
Breault-Dugas
Centre de recherche du Centre hospitalier universitaire (CHU) de Québec - CHUL et Département de médicine moléculaire, Faculté de médecine, Université Laval, Québec, Canada.
Isabelle
I
Pineau
Centre de recherche du Centre hospitalier universitaire (CHU) de Québec - CHUL et Département de médicine moléculaire, Faculté de médecine, Université Laval, Québec, Canada.
Sébastien A
SA
Lévesque
Department of Neurosciences, Faculty of Medicine, Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), and Groupe de recherche sur le système nerveux central (GRSNC), Université de Montréal, Quebec, Canada.
Catherine-Alexandra
CA
Grégoire
Department of Neurosciences, Faculty of Medicine, Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), and Groupe de recherche sur le système nerveux central (GRSNC), Université de Montréal, Quebec, Canada.
Karl J L
KJ
Fernandes
D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D049109:Cell Proliferation; D004681:Encephalomyelitis, Autoimmune, Experimental; D004805:Ependyma / Q000166:cytology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007796:Laminectomy; D008244:Lysophosphatidylcholines; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D058953:Neural Stem Cells / Q000166:cytology* / Q000502:physiology; D013115:Spinal Canal / Q000166:cytology*; D013119:Spinal Cord Injuries / Q000503:physiopathology*
D008244:Lysophosphatidylcholines