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Molecular targets in spinal cord injury

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Abstract

The spinal cord can be compared to a highway connecting the brain with the different body levels lying underneath, with the axons being the ultimate carriers of the electrical impulse. After spinal cord injury (SCI), many cells are lost because of the injury. To reconstitute function, damaged axons from surviving neurons have to grow through the lesion site to their initial targets. However, the territory they have to traverse has changed: the highway is full of inhibitory signals (myelin and scar components); the pavement itself has become bumpy (demyelination); and specialized cells are recruited to clear the way (inflammatory cells). Thus, actual strategies to treat spinal injuries aim at providing a permissive environment for regenerating axons and boosting the endogenous potential of axons to regenerate while limiting progression of secondary damage. Here we review some of the strategies currently under consideration to treat spinal injuries.

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Abbreviations

SCI:

Spinal cord injury

ATP:

Adenosine triphosphate

NMDA:

N-methyl-d-aspartate

AMPA:

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

NASCIS:

National Acute Spinal Cord Injury Study

NO:

Nitric oxide

NOS:

Nitric oxide synthase

4-AP:

4-Aminopyridine

MP:

Methylprednisolone

MMP:

Matrix metalloprotease

ICAM-1:

Intercellular adhesion molecule-1

VCAM-1:

Vascular cell adhesion molecule-1

TNF:

Tumor necrosis factor

IL:

Interleukin

PG:

Prostaglandin

COX:

Cyclooxygenase

MBP:

Myelin basic protein

zVAD-fmk:

N-Benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone

p75NTR:

p75 neurotrophin receptor

CD95L:

CD95 ligand

BBB:

Blood–brain barrier

CSPGs:

Chondroitin sulfate proteoglycans

OMgp:

Oligodendrocyte myelin glycoprotein

MAG:

Myelin-associated glycoprotein

NgR:

Nogo receptor

ROCK:

RhoA-associated kinase

OECs:

Olfactory ensheathing cells

OPCs:

Oligodendrocyte precursor cells

MS:

Multiple sclerosis

DRG:

Dorsal root ganglion

cAMP:

Cyclic adenosine monophosphate

PKA:

Protein kinase-A

BDNF:

Brain-derived neurotrophic factor

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Acknowledgements

This paper is dedicated to M. Hergenhahn (deceased). We thank Ian Paul Martin for graphic design. We thank Susanne Kleber, Elisabeth Letellier, Nina Schreglmann, Henriette Uhlenhaut, Renee Wegrzyn, Cecilia Zuliani and Prof. Peter H. Krammer for critical reading. We also thank Prof. Manfred Zimmermann for the financial support of Deana Demjen. This work was supported by the Christopher Reeve Paralysis Foundation (grant KAC2-0101-2 and MA2-0301-2).

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  1. Tumorimmunology Program, Division of Immunogenetics, German Cancer Research Center, Heidelberg, Germany

    Stefan Klussmann & Ana Martin-Villalba

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Klussmann, S., Martin-Villalba, A. Molecular targets in spinal cord injury. J Mol Med 83, 657–671 (2005). https://doi.org/10.1007/s00109-005-0663-3

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