Molecular mechanism of neuroprotective action by grafted neuroectodermal stem cells following injury to spinal motoneurones
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1
University of Szeged, Department of Ophthalmology, Faculty of Medicine, Hungary
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2
Ludwig Boltzmann Institute for experimental and clinical Traumatology, Austria
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3
University of Veterinary Medicine, VetOMICS, Austria
Avulsion of ventral roots containing the axons of motoneurones induces the death of majority of affected cells by 2 weeks after injury. Similar avulsion injury occurs in human brachial or lumbar plexus injuries. Our previous studies have shown that motoneuron death induced by avulsion of the lumbar 4 (L4) ventral root can be prevented by grafting clonal neuroectodermal stem cells into the L4 segment. In this study we investigated the molecular mechanisms of neuroprotective action of grafted neuroectodermal stem cells.
The lumbar spinal cord of Sprague Dawley adult rats was exposed, the L4 left ventral root was avulsed and 300000 clonal neuroectodermal stem cells were implanted into the caudal part of the L4 segment. Then the L4 ventral root was reimplanted close to the site of grafting. Control animals received no stem cells but underwent L4 ventral root avulsion and reimplantation. Rats were allowed to survive for 5, 10 or 14 days then their L4 spinal segment was removed. Semiquantitative PCRs were performed to evaluate the amounts of mRNA of various immune factors (IL-1-alpha, IL-1-beta, IL-6, IL-10, MCP-1, MIP-1-alpha, MCSF, and TNF-alpha) and neurotrophic factors (BDNF, GDNF, NT4, PDGF-alpha, PDGF-beta, PTN, and TGF-beta).
Considerable increase of immune factor mRNA levels was observed 5 days after injury in the grafted cords and these mRNA levels were maintained at 10 days. All the elevated mRNA levels returned to that of controls by 14 days after injury. No significant change in the levels of neurotrophic factor mRNAs, except for PDGF-alpha was found at any time point.
These results suggest that immune factors (especially IL-1-alpha, IL-6, IL-10, MIP-1-alpha, and TNF-alpha) rather than neurotrophic factors play key roles in rescuing motoneurones. The timescale of the molecular changes appear to collerate with motoneuron survival.
Further studies are under way to determine the exact role of these factors in the rescue mechanisms of injured motoneurones.
Conference:
IBRO International Workshop 2010, Pécs, Hungary, 21 Jan - 23 Jan, 2010.
Presentation Type:
Poster Presentation
Topic:
Disorders of the nervous system
Citation:
Pajer
K,
Feichtinger
G,
Klein
D,
Redl
H and
Nógrádi
A
(2010). Molecular mechanism of neuroprotective action by grafted neuroectodermal stem cells following injury to spinal motoneurones.
Front. Neurosci.
Conference Abstract:
IBRO International Workshop 2010.
doi: 10.3389/conf.fnins.2010.10.00056
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Received:
20 Apr 2010;
Published Online:
20 Apr 2010.
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Correspondence:
Krisztian Pajer, University of Szeged, Department of Ophthalmology, Faculty of Medicine, Szeged, Hungary, pajer.krisztian@gmail.com