Thalidomid und Rolipram führen zu funktionell relevanten Verbesserungen der Motorik nach traumatischen Rückenmarksverletzungen bei der Ratte

Traumatic spinal cord injury (SCI) causes permanent motor, sensory and autonomic deficits. The primary lesion characterised by the initial mechanic tissue damage is following by a cascade of secondary tissue degeneration. The release of potent pro-inflammatory cytokines tumour necrosis factor alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) play important roles during the early hours after injury. This period of secondary tissue degeneration presents an early therapeutic window of opportunity, during which intervention strategies directed at reducing the influence of such cytokines could deliver significant beneficial effects. In the present thesis, the ability of rolipram and thalidomide (FDA approved drugs) to reduce secondary tissue degeneration was assessed in an experimental model of moderate contusion-type, SCI in adult rats. A single intraperitoneal administration of both drugs administered immediately after injury, resulted in a statistically significant improvement in white matter sparing at the lesion epicentre. Furthermore the cellular distribution pattern of TNF alpha and IL-1 beta immunoreactive profiles in both healthy and lesion spinal cords was assessed, as well as possible indications of sparing or sprouting of descending, Raphe nucleus-derived serotonergic fibres (a population of fibres reported to play a role in the activation of the central pattern generator of the lumbal spinal cord). At present there is no widely accepted intervention strategy for the early treatment of human SCI, apart from the surgical stabilisation of spinal vertebrae and eventual rehabilitation. The present data, therefore, demonstrates the potential therapeutic benefits of applying already established pharmaca to other medical applications. The use of such an “off the shelf” approach might provide immediately accessible benefits for patients suffering from spinal cord injury today while other, more specific strategies are undergoing expensive and time-consuming clinical trials.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2009

Author dc:creator

• Kern, Nadine

Contributors dc:contributor

• Brook, Gary

• info:eu-repo/classification/ddc/610
• Rückenmarksverletzung
• Thalidomid
• Rolipram
• Motorik
• Interleukin 1-beta
• Tumor-Nekrose-Faktor <alpha>
• Medizin
• spinal cord injury
• thalidomide
• tumour necrosis factor alpha

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113703%22

OAI record oai:identifier

https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A51411