Epileptogenic effect of cyclosporine in guinea-pig hippocampal slices.
Cyclosporine A (CsA) neurotoxicity is a common cause of seizures in transplant patients and others receiving immunosuppressive therapy. CsA at concentrations higher than the levels estimated for cerebrospinal fluid of the patients suffering from seizure attacks was ineffective to induce epileptiform field potentials (EFP) in in vitro brain-slice preparation. The aim of this study was to test the effect of CsA at lower concentrations on neuronal activity. Guinea-pig hippocampal slices were exposed to artificial cerebrospinal fluid containing CsA (0.1-2 microM). Furthermore, the effects of CsA (0.25-10 microM) were tested on EFP elicited by omission of Mg2+ from superfusate. Low concentrations of CsA (0.1-0.25 microM) induced EFP while higher doses (0.5-2 microM) failed to decrease the seizure threshold. CsA at concentrations of 0.25 and 1 microM had no significant effect on the low Mg2+-induced EFP. Higher CsA concentration (10 microM) strongly suppressed EFP. The results indicate that CsA at doses that are probably clinically relevant increases the neuronal excitability.
Gorji
A
A
Institut für Physiologie, Universität Münster, Robert-Koch-Strasse 27a, 48149, Münster, Germany. gorjial@uni-muenster.de
Scheld
H H
HH
Speckmann
E-J
EJ
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology; D016572:Cyclosporine / Q000009:adverse effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000139:chemically induced* / Q000503:physiopathology; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008275:Magnesium Deficiency / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009924:Organ Culture Techniques
D007166:Immunosuppressive Agents; D016572:Cyclosporine