Proper management of chemotoxicity in transplant patients requires detailed knowledge of the biochemical mechanisms underlying
immunosuppressant toxicity. Neurotoxicity is one of the most significant clinical side effects of the immunosuppressive undecapeptide
cyclosporine, occurring at some degree in up to 60% of transplant patients. The clinical symptoms of
cyclosporine-mediated neurotoxicity consist of decreased responsiveness,
hallucinations, delusions,
seizures,
cortical blindness, and
stroke-like episodes that mimic those clinical symptoms of
mitochondrial encephalopathy. Clinical computed tomography (CT) and magnetic resonance imaging (MRI) studies have revealed a correlation between clinical symptoms of
cyclosporine-mediated neurotoxicity and morphological changes in the brain, such as hypodensity of white matter,
cerebral edema,
metabolic encephalopathy, and hypoxic damages. Paradoxically, in animal models
cyclosporine protects the brain from
ischemia-reperfusion (I/R) injury. Interestingly,
cyclosporine appears to mediate both neurotoxicity (under normoxic conditions) and I/R protection across the same range of
drug concentration. Both toxicity and protection might arise from the intersection of
cyclosporine with mitochondrial energy metabolism. This review addresses basic biochemical mechanisms of: 1)
cyclosporine toxicity in normoxic brain, and 2) its protective effects in the same organ during I/R. The marked and unparallel potential of magnetic resonance spectroscopy (MRS) as a novel quantitative approach to evaluate metabolic
drug toxicity is described.