Publications by authors named "B Kuhne"

Article Synopsis
  • In Europe, rodent studies are the main method used to assess neurotoxicity, but they are expensive and raise ethical concerns, leading many to seek alternatives.
  • There is a growing public demand for safer chemicals, as many on the market haven't been thoroughly tested for neurotoxic effects, prompting research into New Approach Methods (NAMs) to replace animal testing.
  • The European Partnership for the Assessment of Risks from Chemicals (PARC) is working on NAMs to evaluate neurotoxicity, aiming to create faster and cheaper testing methods that can help regulatory agencies and industries improve safety assessments.
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This case study explores the applicability of transcriptome data to characterize a common mechanism of action within groups of short-chain aliphatic α-, β-, and γ-diketones. Human reference data indicate that the α-diketone diacetyl induces bronchiolitis obliterans in workers involved in the preparation of microwave popcorn. The other three α-diketones induced inflammatory responses in preclinical animal studies, whereas beta and gamma diketones in addition caused neuronal effects.

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Introduction: Intrauterine growth restriction (IUGR) is a well-known cause of impaired neurodevelopment during life. In this study, we aimed to characterize alterations in neuronal development underlying IUGR and discover strategies to ameliorate adverse neurodevelopment effects by using a recently established rabbit in vitro neurosphere culture.

Methods: IUGR was surgically induced in pregnant rabbits by ligation of placental vessels in one uterine horn, while the contralateral horn remained unaffected for normal growth (control).

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Following a multi-disciplinary approach integrating information from several experimental models we have collected new evidence supporting, expanding and redesigning the AOP "Disrupted laminin/int-β1 interaction leading to decreased cognitive function". Investigations in vitro in rabbit and rat neurospheres and in vivo in mice exposed to EGCG (epigallocatechin-gallate) during neurodevelopment are combined with in vitro evaluations in neural progenitor cells overexpressing int-β1 and literature information from int-β1 deficiency models. We have discovered for the first time that neural progenitor cells from intrauterine growth restricted (IUGR) animals overexpress int-β1 at gene and protein level and due to this change in prenatal brain programming they respond differently than control neurospheres to the exposure of EGCG, a compound triggering neural progenitor cell migration alterations.

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Article Synopsis
  • - The rabbit model is increasingly valued in neurodevelopmental studies due to its closer resemblance to human brain development compared to rodents.
  • - The publication outlines 14 detailed protocols focusing on various toxicological endpoints to evaluate neurodevelopmental adverse effects in rabbits, spanning from the neonatal phase to long-term assessments.
  • - Each protocol includes expected control values, troubleshooting tips, and addresses techniques like neurosphere assays, behavioral tests, and neurohistopathological evaluations, making it a thorough resource for researchers.
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