Potential adverse effects of cyclosporin A on kidneys after spinal cord injury.
METHODS
Cell transplantation strategies are gaining increasing interest for spinal cord injury (SCI) with the objective of promoting spinal cord repair. To avoid allogenic graft rejection, an adequate immune suppression is required, and one of the most potent and commonly used immunosuppressives is cyclosporin A (CsA). In SCI, permanent sensory motor loss is combined with modifications of drug absorption, distribution and elimination.


OBJECTIVE
The objectives of this study were to thoroughly explore histological and functional outcomes of CsA treatment in a rat model of spinal cord compression.


METHODS
Experiments were carried out at the Institute for Neurosciences of Montpellier (France), the Integrative Biology of Neurodegeneration Laboratory (Spain) and in the Novartis Institutes for BioMedical Research (Switzerland) for CsA blood concentration determination.


METHODS
We first evaluated histological outcomes of CsA treatment on kidneys and spinal cord after SCI. We then investigated whether SCI modified CsA blood concentration. Finally, using behavioral analysis, we assessed the potential CsA impact on functional recovery.


RESULTS
When spinal-cord-injured rats were treated with a CsA dose of 10 mg kg(-1) per day, we observed deleterious effects on kidneys, associated with modifications of CsA blood concentration. Adding an antibiotic treatment reduced kidney alteration without modifying CsA blood concentration. Finally, we showed that CsA treatment per se modified neither functional recovery nor lesion extension.


CONCLUSIONS
This study pinpoints the absolute requirement of careful CsA monitoring in the clinical setting for patients with SCI to minimize potential unexpected effects and avoid therapeutic failure.
Lonjon
N
N
INSERM U583, Institute for Neurosciences of Montpellier, Pathophysiology and Therapy of Sensory and Motor Deficits, Saint Eloi Hospital, Montpellier Cedex 05, France.
Boniface
G
G
Feifel
R
R
Endres
R
R
Gimenez y Ribotta
M
M
Privat
A
A
Perrin
F E
FE
D000818:Animals; D017690:Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D016572:Cyclosporine / Q000097:blood / Q000627:therapeutic use / Q000633:toxicity*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000379:methods; D006084:Graft Rejection / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use / Q000633:toxicity; D007674:Kidney Diseases / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000503:physiopathology* / Q000601:surgery; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016572:Cyclosporine