Division of Neonatology, Careggi University Hospital of Florence, Florence, Italy,
Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy,
Neonatology. 2019;115(3):217-225. doi: 10.1159/000494101. Epub 2019 Jan 15.
The physiopathology of bilirubin-induced neurological disorders is not completely understood.
The aim of our study was to assess the effect on bilirubin neurotoxicity of the maturity or immaturity of exposed cells, the influence of different unconjugated bilirubin (UCB) and human serum albumin (HSA) concentrations, and time of UCB exposure.
Organotypic hippocampal slices were exposed for 48 h to different UCB and HSA concentrations after 14 (mature) or 7 (immature) days of in vitro culture. Immature slices were also exposed to UCB and HSA for 72 h. The different effects of exposure time to UCB on neurons and astrocytes were evaluated.
We found that 48 h of UCB exposure was neurotoxic for mature rat organotypic hippocampal slices while 72 h of exposure was neurotoxic for immature slices. Forty-eight-hour UCB exposure was toxic for astrocytes but not for neurons, while 72-h exposure was toxic for both astrocytes and neurons. HSA prevented UCB toxicity when the UCB:HSA molar ratio was ≤1 in both mature and immature slices.
We confirmed UCB neurotoxicity in mature and immature rat hippocampal slices, although immature ones were more resistant. HSA was effective in preventing UCB neurotoxicity in both mature and immature rat hippocampal slices.
胆红素引起的神经功能紊乱的病理生理学尚未完全阐明。
我们的研究旨在评估暴露细胞的成熟度或不成熟度、不同未结合胆红素（UCB）和人血清白蛋白（HSA）浓度以及 UCB 暴露时间对胆红素神经毒性的影响。
在体外培养 14 天（成熟）或 7 天后（不成熟），将器官型海马切片暴露于不同的 UCB 和 HSA 浓度下 48 小时。不成熟的切片还暴露于 UCB 和 HSA 中 72 小时。评估 UCB 暴露时间对神经元和星形胶质细胞的不同影响。
我们发现，48 小时的 UCB 暴露对成熟大鼠器官型海马切片具有神经毒性，而 72 小时的暴露对不成熟切片具有神经毒性。48 小时的 UCB 暴露对星形胶质细胞有毒性，但对神经元没有毒性，而 72 小时的暴露对星形胶质细胞和神经元都有毒性。当 UCB：HSA 摩尔比在成熟和不成熟的切片中均≤1 时，HSA 可预防 UCB 毒性。
我们证实了成熟和不成熟大鼠海马切片中 UCB 的神经毒性，尽管不成熟的切片更具抵抗力。HSA 可有效预防成熟和不成熟大鼠海马切片中 UCB 的神经毒性。
