Affiliations: Group of Neuroplasticity and Regeneration, Institute
of Neurosciences, Department of Cell Biology, Physiology and Immunology, and
Centro de Investigación Biomédica en Red sobre Enfermedades
Neurodegenerativas (CIBERNED), Universitat Autònoma de Barcelona,
Bellaterra, Spain
Note: [] Corresponding author: Dra. Caty Casas, Unitat de Fisiologia
Mèdica, Edif. M, Universitat Autònoma de Barcelona, E-08193
Bellaterra, Spain. Tel.: +34 935811348; Fax: +34 935812986; E-mail:
caty.casas@uab.cat
Abstract: Purpose: Damage to segmental motoneurons and to spinal cord
parenchyma cause denervation atrophy to the muscles, contributing to the
chronic disability originated by spinal cord injury (SCI) and spinal motor
neuron diseases. After SCI, damage is promoted by several underlying
mechanisms, including release of glutamate and consequent over-activation of
glutamate receptors, mainly NMDA receptors, that lead to neuronal death. Due to
the lack of effective treatments for such conditions, new alternatives need to
be explored. Methods: In order to perform a relatively quick and high-fidelity
drug screening, we optimized a postnatal rat organotypic spinal cord culture.
By using a glutamate excitotoxic model of spinal cord damage on the explants,
we compared the neuroprotective efficacy of four agents: methylprednisolone,
erythropoietin, riluzole and rolipram. We evaluated the number of surviving
ventral motor neurons stained with the SMI32 antibody and estimated the cord
tissue preservation by quantifying the amount of EthD fluorescent probe
incorporated into the cells. Results: The best tissue protection was achieved with riluzole (98%)
whereas the highest motoneuron preservation was obtained with
methylprednisolone (92%). Conclusion: The in vitro model used may serve to initiate
comparative analyses of new compounds to narrow the choice for future
neuroprotective agents to be tested in vivo.
Keywords: Spinal cord injury, motor neuron disease, NMDA, neurodegeneration, rat
