Restorative Neurology and Neuroscience - Volume 19, issue 1-2

Authors: Fricker-Gates, Rosemary A. | Lundberg, Cecilia | Dunnett, Stephen B.

Article Type: Research Article

Abstract: During the last 30 years, the promise of neural transplantation as a therapeutic strategy for neurodegenerative disease has been slowly recognised. Across the world, clinical transplants of embryonic primary dopamine neurones have been shown to ameliorate some of the motor deficits in Parkinsons disease (PD) patients, and more recently, systematic clinical trials have been initiated for the replacement of striatal pro-jection neurones lost in Huntington's disease (HD) . Clinical transplantation as a prospective therapy …for HD poses a particular set of difficulties. The hallmarks of this neurodegenerative disease include extensive loss of medium spiny long-distance projection neurones of the caudate and putamen, affecting downstream target nuclei, the globus pallidus and substantia nigra, leading to dysregulation of motor control. In addition, extensive loss of cortical neurones that form the afferent systems to the basal ganglia leads to widespread cognitive decline. If transplantation therapy is to succeed in replacing degenerating neurones in HD and reinstating controlled function of complex basal gan-glia circuitry, the new neurones must be able to develop specific long-distance projections that can form accurate and functional connections with neurones in precise target regions. Our ongoing studies are aimed at addressing how we can improve the function of striatal transplants, in particular to optimise the reforma-tion of precise long-distance connections and to re-establish normal motor and cognitive function. In particular, we have investigated optimal requirements for embryonic primary tissue to achieve these aims, and also the potential of other cell sources to provide long-distance projection neurones and reconnect complex circuitry. This review describes current progress of experiments to optimise the reconstruction of neu-ronal circuitry using primary embryonic tissue transplants, as well as our current initiatives to use neural stem cells or precursors to replace long distance projection neurones in the degenerating basal ganglia. Show more

Keywords: transplantation, neuronal differentiation, behaviour, function, connectivity, Huntingtons Disease, striatum, neural progenitors

Citation: Restorative Neurology and Neuroscience, vol. 19, no. 1-2, pp. 119-138, 2001

Authors: Hermanns, Susanne | Klapka, Nicole | Müller, Hans Werner

Article Type: Research Article

Abstract: After CNS trauma a sheet-like, collagen type IV (Coll IV) immunopositive basement membrane (BM) develops in the lesion zone as well as at newly formed blood vessels. The basic scaffold of this BM is composed of Coll IV, laminin and nidogen but numerous other proteins some of which are discussed to be inhibitory for axonal regeneration, i.e. chondroitin- and heparansufate-proteoglycans, are associated with BM. This review will focus on the collagenous wound healing scar, discuss its …composition and summarize the experimental results that demonstrate its role in the failure of axonal regeneration in the injured mammalian CNS. Show more

Keywords: basement membrane, glial scar, CNS trauma, collagen IV, extracellular matrix,

Citation: Restorative Neurology and Neuroscience, vol. 19, no. 1-2, pp. 139-148, 2001

Authors: Ramón-Cueto, Almudena | Santos-Benito, Fernando F.

Article Type: Research Article

Abstract: The absence of spontaneous axonal regeneration in the adult mammalian central nervous system cause devastating functional consequences in patients with spinal cord injuries. During the past decades several attempts have been made in order to find a strategy to repair injured spinal cords in experimental animals, that could provide a novel therapeutic approach in humans. Cell transplantation has been broadly used as an intervention to influence neuronal survival and axonal regeneration in the severed neuraxis. Of …the cell types used for transplantation, olfactory ensheathing glia (OEG) promoted a dramatic functional improvement and anatomical repair after complete transection of the adult mammalian spinal cord. These cells can be easily obtained from adult donors opening the possibility of autologous transplantation. Grafting OEG to repair injured spinal cords offers some advantages compared to injections of other cell types. Therefore, OEG have become good candidates to bring about repair in damaged spinal cords. In this article we review OEG transplantation studies, discuss the properties that could account for their axonal growth-promoting ability, and the advantages of using OEG as a repair strategy. Show more

Keywords: axonal regeneration, spinal cord injury, functional recovery, Schwann cells, astrocytes, glial scar, cell migration, demyelination

Citation: Restorative Neurology and Neuroscience, vol. 19, no. 1-2, pp. 149-156, 2001