title: On the fate of extracellular hemoglobin and heme in brain.
abstract: 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.
authors.affiliation: Laboratório de Morfogênese Celular, Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Cidade Universitária, Rio de Janeiro, Brazil. falara@ioc.fiocruz.br
authors.forename: Flavio A
authors.initials: FA
authors.lastname: Lara
authors.forename: Suzana A
authors.initials: SA
authors.lastname: Kahn
authors.forename: Anna Cc
authors.initials: AC
authors.lastname: da Fonseca
authors.forename: Carlomagno P
authors.initials: CP
authors.lastname: Bahia
authors.forename: João Pc
authors.initials: JP
authors.lastname: Pinho
authors.forename: Aurélio V
authors.initials: AV
authors.lastname: Graca-Souza
authors.forename: Jean C
authors.initials: JC
authors.lastname: Houzel
authors.forename: Pedro L
authors.initials: PL
authors.lastname: de Oliveira
authors.forename: Vivaldo
authors.initials: V
authors.lastname: Moura-Neto
authors.forename: Marcus F
authors.initials: MF
authors.lastname: Oliveira