Effects of cyclosporin-A on immune response, tissue protection and motor function of rats subjected to spinal cord injury.
The aim of this work was to test the effect of cyclosporin-A (CsA) on some immunological, morphological and functional aspects developed after spinal cord injury. The specific cellular immune response against spinal cord constituents, the amount of spared tissue and myelination at the site of injury, and the motor function outcome were assessed in a first series of experiments. Rats were subjected to spinal cord compression and treated with cyclosporin-A before lesion and during the entire study. A specific lymphocyte response against spinal cord antigens was found in untreated spinal cord injured rats but not in cyclosporine-A treated injured rats. A significantly better myelination index was also found in injured cyclosporin-A-treated rats, as compared to untreated animals. The amount of spared spinal cord tissue at the epicenter was not significantly different comparing CsA-treated with vehicle-treated rats. Looking for a potential therapeutic use of CsA, in a second series of experiments, rats were subjected to spinal cord contusion and treated with cyclosporin-A from 1 to 72 h after lesion. Motor recovery and red nuclei neurons survival, were evaluated, and found to be significantly better in spinal cord injured rats treated with cyclosporin-A than in injured-untreated rats. This work confirms the existence of an autoimmune cellular reaction after injury that can be inhibited by cyclosporin-A treatment. Furthermore, cyclosporin-A promotes neuroprotection by diminishing both demyelination and neuronal cell death, resulting in a better motor outcome after spinal cord injury.
Ibarra
Antonio
A
Unidad de Investigación Médica en Enfermedades Neurológicas, Centro Médico Nacional Siglo XXI, IMSS, DF, México, Mexico. iantonio65@yahoo.com
Correa
Dolores
D
Willms
Kaethe
K
Merchant
Marie Therese
MT
Guizar-Sahagún
Gabriel
G
Grijalva
Israel
I
Madrazo
Ignacio
I
D000818:Animals; D001369:Axons / Q000473:pathology / Q000648:ultrastructure; D016572:Cyclosporine / Q000097:blood / Q000494:pharmacology*; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects; D008854:Microscopy, Electron; D009043:Motor Activity / Q000187:drug effects*; D009186:Myelin Sheath / Q000187:drug effects / Q000648:ultrastructure; D051381:Rats; D013116:Spinal Cord / Q000473:pathology / Q000648:ultrastructure; D013117:Spinal Cord Compression / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D013904:Thoracic Vertebrae; D013997:Time Factors
D007166:Immunosuppressive Agents; D016572:Cyclosporine