Experimental strategies to promote spinal cord regeneration—an integrative perspective
Section snippets
Epidemiology and clinic
Given an increasing incidence of spinal cord injury and an almost unaltered life time expectation, it has been estimated that 2.5 million spinal cord injured patients are living worldwide. In comparison to Europe the incidence of SCI in the US is higher, mainly due to gunshot wounds (DeVivo, 1997, McDonald, 1999, The National SCI Statistical Center, 2001). About 40% of the patients suffer from quadriplegia, 60% from paraplegia. In about 60% of the patients, the sensory and/or motor paralysis is
Pathophysiology—an update
Upon initial impact the vertebral fracture causes a local, segmental-limited damage of the spinal cord (primary damage, Fig. 1, Fig. 2). As a consequence of rupture or contusion of axons, hemorrhage, ischemia and edema develops. The damage considerably expands during the first weeks due to further destruction of neuronal and glial cells (secondary damage, Fig. 2) (Tator, 1995, Tator, 1998). First, the lesion expands vertically through the gray matter; and then spreads further horizontally
Neuronal and glial protection
To reduce the formation of cytotoxic edema, inflammation and the release of glutamate and free radicals (Fig. 2B and C) a high dose of methylprednisolone (30 mg/kg) can be administered during the early acute phase (<8 h). However, this treatment is still controversial (Short, 2000, Short et al., 2000, Hurlbert, 2001). In the United States this therapy is frequently applied. On the contrary, not all European centers are using methylprednisolone, since it leads to a higher rate of complications
Causes for the lack of substances with unquestionable clinical effectiveness
For several reasons it is difficult (see below) to transfer successful experimental results (Wickelgren, 2002) to the clinical situation (Pearson, 2003). In some aspects this due to species differences between rodents and human, for example, in the case of glial reactions upon spinal cord injury (Puckett et al., 1997, Norenberg et al., 2004, Kakulas, 2004). In addition, compensatory mechanisms upon SCI are more frequently observed in rodents compared to humans. On the clinical side problems in
Future prospects
The possibility to specifically direct the axonal growth towards the original deafferenting site is still in the distant future (McDonald and Sadowsky, 2002). The fact, however, that merely 10% of the original axons are necessary to achieve a significant functional improvement in rodents (Barnett et al., 2000, Blight, 1983) gives reason for hope, as well as the fact that an important part of the distal axon ends still remain at the lesion for a long time after the spinal cord injury (Hill et
Acknowledgements
This work is supported by the Wings for Life Spinal Cord Research Foundation. JMS was awarded by an international “poste rouge” scholarship of the Centre National de la Recherche Scientifique (CNRS), France and is at present a Research Fellow supported by the German Research Council (DFG), #1164/1-1. We would like to thank Dr. Kattie Luyten and Simone Mucha for their help in preparing the manuscript.
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