Lara Flavio A, Kahn Suzana A, da Fonseca Anna Cc, Bahia Carlomagno P, Pinho João Pc, Graca-Souza Aurélio V, Houzel Jean C, de Oliveira Pedro L, Moura-Neto Vivaldo, Oliveira Marcus F
Laboratório de Morfogênese Celular, Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Cidade Universitária, Rio de Janeiro, Brazil.
J Cereb Blood Flow Metab. 2009 Jun;29(6):1109-20. doi: 10.1038/jcbfm.2009.34. Epub 2009 Apr 1.
Intracerebral hemorrhage (ICH) is a major cause of disability in adults worldwide. The pathophysiology of this syndrome is complex, involving both inflammatory and redox components triggered by the extravasation of blood into the cerebral parenchyma. Hemoglobin, heme, and iron released therein seem be important in the brain damage observed in ICH. However, there is a lack of information concerning hemoglobin traffic and metabolism in brain cells. Here, we investigated the fate of hemoglobin and heme in cultured neurons and astrocytes, as well as in the cortex of adult rats. Hemoglobin was made traceable by conjugation to Alexa 488, whereas a fluorescent heme analogue (tin-protoporphyrin IX) was prepared to allow heme tracking. Using fluorescence microscopy we observed that neurons were more efficient in uptake hemoglobin and heme than astrocytes. Exposure of cortical neurons to hemoglobin or heme resulted in an oxidative stress condition. Viability assays showed that neurons were more susceptible to both hemoglobin and heme toxicity than astrocytes. Together, these results show that neurons, rather than astrocytes, preferentially take up hemoglobin-derived products, indicating that these cells are actively involved in the ICH-associated brain damage.
脑出血（ICH）是全球成年人残疾的主要原因。该综合征的病理生理学很复杂，涉及血液渗入脑实质引发的炎症和氧化还原成分。其中释放的血红蛋白、血红素和铁似乎在脑出血中观察到的脑损伤中起重要作用。然而，关于脑细胞中血红蛋白的运输和代谢的信息却很匮乏。在这里，我们研究了培养的神经元和星形胶质细胞以及成年大鼠皮质中血红蛋白和血红素的去向。通过与Alexa 488偶联使血红蛋白可被追踪，同时制备了一种荧光血红素类似物（锡原卟啉IX）以进行血红素追踪。使用荧光显微镜，我们观察到神经元摄取血红蛋白和血红素的效率比星形胶质细胞更高。将皮质神经元暴露于血红蛋白或血红素会导致氧化应激状态。活力测定表明，神经元比星形胶质细胞对血红蛋白和血红素毒性更敏感。总之，这些结果表明，神经元而非星形胶质细胞优先摄取血红蛋白衍生的产物，表明这些细胞积极参与了与脑出血相关的脑损伤。
