Epileptogenic effect of cyclosporine in guinea-pig hippocampal slices.

Institut für Physiologie, Universität Münster, Robert-Koch-Strasse 27a, 48149, Münster, Germany.
Neuroscience (Impact Factor: 3.33). 02/2002; 115(4):993-7. DOI: 10.1016/S0306-4522(02)00507-9
Source: PubMed

ABSTRACT 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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although ulcerative colitis and Crohn’s disease have traditionally been considered to be inflammatory diseases limited to the gastrointestinal tract, it has been shown that both pathologies are frequently accompanied by various extraintestinal disorders. There is an increasing evidence that they may also manifest in the nervous system, including the peripheral and the central parts. Although some of these neurological complications have been known for a long time, such as cerebrovascular disease, vasculitis and autoinmune processes including neuropathies and cerebral demyelination, others have been recently described. With the exception of some of this complications such as the thromboembolism, evidence for a casual relationship relies merely on single case reports or case series. In this article, we try to review the existing evidence on neurological manifestations of both variants of inflammatory bowel disease.
    Medicina Clinica - MED CLIN. 01/2008; 130(17):666-675.
  • [Show abstract] [Hide abstract]
    ABSTRACT: IntroductionCerebral tumor-like location is uncommon in the course of Behçet's disease. We report herein a patient with tumor-like lesions associated with ciclosporin therapy.Case reportA 45-year-old male treated for 17 years with colchicine and ciclosporin for Behçet's disease with cutaneomucosal, ocular and joint involvement was admitted for sudden onset of meningo-encephalitis with lymphocytic meningitis. CT-scan showed a nodular lesion of the brainstem enhanced by iodine. Ciclosporin was discontinued; prednisone and IV cyclophosphamide were started. After three months of favorable outcome, a relapse occurred when ciclosporin was started again. MRI showed two additional capsulothalamic lesions. Prednisone and cyclophosphamide were started again with a favorable response and minimal sequelae.Conclusion The main challenge in cerebral tumor-like location of Behçet's disease is to rule out other inflammatory or tumor processes. Neuronal toxicity of ciclosporin limits indications for this therapy in Behçet's disease.
    Revue Neurologique 01/2010; 166(10):849-854. · 0.60 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Neurological complications are common in transplant recipients treated with immunosuppressant calcineurin inhibitors. Rapamycin, a macrolide antibiotic, was suggested as an alternative agent in patients who develop calcineurin inhibitor associated neurotoxicity, including seizure attacks. The aim of the present study was to test the effect of rapamycin on the bioelectrical activity and evoked field excitatory postsynaptic potentials (fEPSP) in CA1 area of hippocampal tissues and compare its effect with FK506, a calcineurin inhibitor agent. Application of rapamycin at different concentrations neither affected the bioelectrical activity nor changed fEPSP magnitude. In contrast, FK506 elicited epileptiform burst discharges and significantly enhanced fEPSP magnitude. This study supports the suggestion that rapamycin could be used as an alternative to calcineurin inhibitors in the event of neurotoxicity.
    Epilepsia 05/2007; 48(4):834-6. · 4.58 Impact Factor