Experimental strategies to promote spinal cord regeneration--an integrative perspective.
Detailed pathophysiological findings of secondary damage phenomena after spinal cord injury (SCI) as well as the identification of inhibitory and neurotrophic proteins have yielded a plethora of experimental therapeutic approaches. Main targets are (i) to minimize secondary damage progression (neuroprotection), (ii) to foster axon conduction (neurorestoration) and (iii) to supply a permissive environment to promote axonal sprouting (neuroregenerative therapies). Pre-clinical studies have raised hope in functional recovery through the antagonism of growth inhibitors, application of growth factors, cell transplantation, and vaccination strategies. To date, even though based on successful pre-clinical animal studies, results of clinical trials are characterized by dampened effects attributable to difficulties in the study design (patient heterogeneity) and species differences. A combination of complementary therapeutic strategies might be considered pre-requisite for future synergistic approaches. Here, we line out pre-clinical interventions resulting in improved functional neurological outcome after spinal cord injury and track them on their intended way to bedside.
Schwab
Jan M
JM
Institute of Brain Research, Calwer Str. 3, University of Tuebingen, Medical School, Calwerstr. 3, 72076 Tuebingen, Germany. Jschwab@zeus.bwh.harvard.edu
Brechtel
Klaus
K
Mueller
Christian-Andreas
CA
Failli
Vieri
V
Kaps
Hans-Peter
HP
Tuli
Sagun K
SK
Schluesener
Hermann J
HJ
D000818:Animals; D001369:Axons / Q000502:physiology; D017690:Cell Transplantation / Q000379:methods; D004195:Disease Models, Animal; D006801:Humans; D009414:Nerve Growth Factors / Q000627:therapeutic use; D009416:Nerve Regeneration / Q000502:physiology*; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D020127:Recovery of Function; D013118:Spinal Cord Diseases / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D013234:Stem Cells / Q000502:physiology
D009414:Nerve Growth Factors; D018696:Neuroprotective Agents