Affiliations: Department of Clinical Neuroscience, Department of
Neurosurgery and Neurology, Karolinska Institutet, Karolinska University
Hospital, Stockholm, Sweden | Laboratory of Neurogenesis and Cell Therapy, Section
of Restorative Neurology, Wallenberg Neuroscience Center, Lund University
Hospital, Lund, Sweden
Note: [] Corresponding author: Mikael Svensson, Department of
Neurosurgery, Karolinska Hospital, 171 76 Stockholm, Sweden. Tel.: +46 8
51770000; Fax: +46 8 51771778, E-mail: [email protected]
Abstract: Purpose: Cells in the ependymal region in the adult central nervous
system (CNS) have been found to possess neural progenitor cell (NPC) like
features including capacity for generating new neurons and glia in response to
injury and inflammatory disease. Whether these cells are activated after a
peripheral nerve injury has not previously been extensively evaluated. Methods: We investigate the possible activation and effect of NPCs in the
ependymal region in the immediate vicinity to the hypoglossal nucleus in the
brainstem using two models of injuries, hypoglossal nerve transection and nerve
avulsion after which the proliferation, migration and differentiation of
ependymal regional NPCs were evaluated. Results: We showed that: (i)
immunoreactivity for Sox2 was detected in cells in the ependymal region of the
brainstem and that BrdU/Sox2-positive cells were observed after avulsion, but
not after transection injury; (ii) avulsion induces re-expression of nestin in
the ependymal layer as well as induced NPC migration from the ependymal layer;
(iii) the chemokine SDF-1α (a marker for migrating cells) was
upregulated ipsilateral to the nerve injury; (iiii) the NPCs migrating
differentiated only into GFAP-positive astrocytes in the hypoglossal nucleus. Conclusion: These results suggest that nerve avulsion injury induces in
parallel with the retrograde "axon reaction" activation of endogenous NPCs in
the ependymal region and further suggest that these cells could be involved in
repair and neuroregeneration after injury within the brainstem.
