On the fate of extracellular hemoglobin and heme in brain

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...

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Bibliographic Details
Published in:	Journal of cerebral blood flow and metabolism Vol. 29; no. 6; pp. 1109 - 1120
Main Authors:	Lara, Flavio A, Kahn, Suzana A, Fonseca, Anna CC da, Bahia, Carlomagno P, Pinho, João PC, Graca-Souza, Aurélio V, Houzel, Jean C, de Oliveira, Pedro L, Moura-Neto, Vivaldo, Oliveira, Marcus F
Format:	Journal Article
Language:	English
Published:	London, England SAGE Publications 01-06-2009 Nature Publishing Group Sage Publications Ltd
Subjects:	Animals Astrocytes - metabolism Biological and medical sciences Cells, Cultured Extracellular Space - metabolism Heme - metabolism Hemoglobins - metabolism Investigative techniques, diagnostic techniques (general aspects) Medical sciences Metalloporphyrins - metabolism Nervous system Neurology Neurons - metabolism Oxidative Stress Protoporphyrins - metabolism Rats Rats, Wistar Ultrasonic investigative techniques Vascular diseases and vascular malformations of the nervous system intracerebral hemorrhage orphyrin toxicity trauma reactive oxygen species Oxygen Nervous system diseases Toxicity Cardiovascular disease Trauma Cerebral disorder Encephalon Vascular disease Cerebral hemorrhage Central nervous system disease Hemoglobin Cerebrovascular disease
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Summary:	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.
ISSN:	0271-678X 1559-7016
DOI:	10.1038/jcbfm.2009.34