Neuropsychologic side‐effects of tacrolimus in pediatric renal transplantation

Kemper, Markus J.; Spartà, Giuseppina; Laube, Guido F.; Miozzari, Marco; Neuhaus, Thomas J.

doi:10.1034/j.1399-0012.2003.00028.x

Cited by 52 publications

(39 citation statements)

References 16 publications

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“…Kemper et al determined that following renal transplantation, 9 of 20 children experiencing CsA side-effects had neuropsychological and behavioral symptoms, ranging from anorexia nervosa like symptoms with weight loss and depression [22]. Additionally, Jindal et al noted renal transplantation patients in the cyclosporine era that displayed such emotional problems such as anxiety, hostility, depression, distress, inability to cope, and avoidance behaviors were also at risk for noncompliance [23].…”

Section: Discussionmentioning

confidence: 99%

Chronic Administration of Cyclosporine A Changes Expression of BDNF and TrkB in Rat Hippocampus and Midbrain

et al. 2010

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Neurotrophins, including the brain-derived neurotrophic factor (BDNF), are essential for regulating neuronal differentiation in developing brains. BDNF and its receptor tyrosine kinase receptor B (TrkB) are involved in neuronal signaling, survival and plasticity. Cyclosporine A (CsA) is a potent immunosuppressive agent which prevents allograft rejection in organ transplantation and various immunological diseases. We investigated whether chronic administration of CsA decreases BDNF gene expression in rats, and the influence of CsA on mRNA levels of TrkB receptors was also examined. For 30 days of CsA (10 mg/kg/day) administration, the expression of BDNF and TrkB mRNA was significantly decreased in the hippocampus and midbrain, but there was no significant difference in the cortex. CsA (0, 1, 5 10, 15 ug/ml) down-regulated BDNF and TrkB gene expression through cultured SH-SY5Y cells, as did all-trans retinoic acid (ATRA), and there was no effect on cell viability. These experimental results indicate that suppression of the BDNF and TrkB mRNA, protein level of BDNF expression in the hippocampus and midbrain may be related to altered behavior observed following chronic administration of CsA. A common mechanism of adverse effects of CsA induced depressive symptoms may involve neurotoxicity mediated by down-regulation of brain BDNF and TrkB.

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Section: Discussionmentioning

confidence: 99%

Chronic Administration of Cyclosporine A Changes Expression of BDNF and TrkB in Rat Hippocampus and Midbrain

et al. 2010

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“…Although some exerted satisfactory effects, side effects of these agents hindered further clinical application [10][11][12]. So there is an urgent need to seek for an alternative agent with low toxicity to solve this problem.…”

Section: Introductionmentioning

confidence: 99%

Taurine Reduced Epidural Fibrosis in Rat Models after Laminectomy via Downregulating EGR1

Liu

Tang

Chen

et al. 2016

Cell Physiol Biochem

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Background/Aims: Epidural fibrosis, a common complication after laminectomy, has been demonstrated to be closely associated with poor surgical outcomes. Previous studies showed that taurine had remarkable anti-fibrotic effects on lung and liver fibrosis. We performed this study to investigate the effects of taurine in rat models of epidural fibrosis after laminectomy and to explore the potential molecular mechanism. Methods: Laminectomy was performed on each rat to establish epidural fibrosis model. After taurine treatment, Masson's trichrome and immunohistochemistry staining were used to examine epidural fibrosis. Cell viability was determined using the Cell Counting Kit-8 assay. Annexin V/Propidium Iodide double staining was performed to detect fibroblasts apoptosis. Microarray was adopted to identify significantly changed mRNAs. mRNA expression was measured by qRT-PCR. Lentivirus infection was performed to establish stable knockdown and overexpression cell lines. The expression of fibrosis-related proteins was determined via Western blot. Results: Taurine treatment markedly reduced laminectomy-induced epidural fibrosis in rat models. However, this effect of taurine was independent on TGF-β/Smad pathway, evidenced by no change in the expression of TGF-β and its receptors. Besides, taurine had almost no effect on cell apoptosis. Interestingly, taurine treatment significantly decreased expression of EGR1 (Early growth response protein 1), an enhancer of fibrosis, both in vivo and in vitro. Furthermore, overexpression of EGR1 increased activation of fibroblasts, while EGR1 knockdown achieved an opposite effect, indicating that EGR1 plays a key role in the inhibitory effect of taurine on TGF-β-induced fibrosis. Conclusions: Reduced epidural fibrosis in vivo and decreased activation of fibroblasts in vitro after taurine treatment was mediated by EGR1. Taurine promises to be a potential prevention for epidural fibrosis after laminectomy.

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“…9 School problems, family conflicts, and puberty have been associated with mood symptoms in young transplant patients. 11 Suicidal ideation and attempts are more frequent in adolescents with chronic illnesses and physical disabilities and among those who are dissatisfied with their health. 12,13 In pediatric OLT patients, length of hospitalization and postoperative complications are associated with severity of mood symptoms, but not with suicidal behavior.…”

Section: Discussionmentioning

confidence: 99%