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Brain Advance Access originally published online on October 26, 2005
Brain 2005 128(12):2961-2976; doi:10.1093/brain/awh644
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© The Author (2005). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Olfactory ensheathing glial co-grafts improve functional recovery in rats with 6-OHDA lesions

Saga Johansson, I-Hui Lee, Lars Olson and Christian Spenger

Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden

Correspondence to: Saga Johansson, Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden E-mail: saga.johansson{at}neuro.ki.se

Olfactory ensheathing cells (OEC) transplanted to the site of a spinal cord injury can promote axonal sparing/regeneration and functional recovery. The purpose of this study was to investigate if OEC enhance the effects of grafted dopamine-neuron-rich ventral mesencephalic tissue (VM) in a rodent model of Parkinson's disease. We co-grafted VM with either OEC or astrocytes derived from the same olfactory bulbs as the OEC to rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal system. Co-grafting fetal VM with OEC, but not with astrocytes enhanced dopamine cell survival, striatal reinnervation and functional recovery of amphetamine- and apomorphine-induced rotational behaviour compared with grafting embryonic VM alone. Grafting OEC or astrocytes alone had no effects. Intriguingly, only in the presence of OEC co-grafts, did dopamine neurons extend strikingly long neurites that reached peripheral striatal compartments. Comparable results were observed in a co-culture system where OEC promoted dopamine cell survival and neurite elongation through a mechanism involving both releasable factors and direct contact. Cell type analysis of fetal VM grafts suggested that dopamine neurons of the substantia nigra rather than of the ventral tegmental area were increased in the presence of OEC co-grafts. We conclude that the addition of OEC enhances efficacy of grafted immature dopamine neurons in a rat Parkinson's disease model.

Key Words: transplantation; dopamine neurons; olfactory ensheathing cells; astrocytes; Parkinson's disease

Abbreviations: GFAP = glial fibrillary acidic protein; OEC = olfactory ensheathing cells; SN = substantia nigra; VM = ventral mesencephalic tissue

Received March 1, 2005. Revised August 16, 2005. Accepted August 30, 2005.


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