Acute rolipram/thalidomide treatment improves tissue sparing and locomotion after experimental spinal cord injury
| Autor: | Ronald Deumens, Aye Mu Myint, Liam Geoghegan, Johannes Noth, Gary A. Brook, Wiel H H Honig, Nadine Kern, Armin Buss, Elbert A.J. Joosten, Guido C Koopmans |
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| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Phosphodiesterase Inhibitors Interleukin-1beta Enzyme-Linked Immunosorbent Assay Neuroprotection Central nervous system disease Lesion Developmental Neuroscience Neurofilament Proteins Medicine Animals Spinal cord injury Rolipram Spinal Cord Injuries business.industry Tumor Necrosis Factor-alpha Myelin Basic Protein Recovery of Function medicine.disease Surgery Nerve Regeneration Rats Thalidomide Clinical trial Tissue Degeneration Disease Models Animal Neurology Gene Expression Regulation Rats Inbred Lew Anesthesia Disease Progression Drug Therapy Combination medicine.symptom business Immunosuppressive Agents Locomotion Psychomotor Performance medicine.drug |
| Zdroj: | Experimental neurology. 216(2) |
| ISSN: | 1090-2430 |
| Popis: | Traumatic spinal cord injury (SCI) causes severe and permanent functional deficits due to the primary mechanical insult followed by secondary tissue degeneration. The cascade of secondary degenerative events constitutes a range of therapeutic targets which, if successfully treated, could significantly ameliorate functional loss after traumatic SCI. During the early hours after injury, potent pro-inflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) are synthesized and released, playing key roles in secondary tissue degeneration. In the present investigation, the ability of rolipram and thalidomide (FDA approved drugs) to reduce secondary tissue degeneration and improve motor function was assessed in an experimental model of spinal cord contusion injury. The combined acute single intraperitoneal administration of both drugs attenuated TNF-alpha and IL-1beta production and improved white matter sparing at the lesion epicenter. This was accompanied by a significant (2.6 point) improvement in the BBB locomotor score by 6 weeks. There is, at present, no widely accepted intervention strategy that is appropriate for the early treatment of human SCI. The present data suggest that clinical trials for the acute combined application of rolipram and thalidomide may be warranted. The use of such "established drugs" could facilitate the early initiation of trials. |
| Databáze: | OpenAIRE |
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