Cássia Righy1,2, Ricardo Turon2,3, Gabriel de Freitas4,5, André Miguel Japiassú1, Hugo Caire de Castro Faria Neto6, Marcelo Bozza7, Marcus F Oliveira8, Fernando A Bozza1,9. 1. Laboratório de Pesquisa Clínica em Medicina Intensiva, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz - Rio de Janeiro (RJ), Brasil. 2. Instituto Estadual do Cérebro Paulo Niemeyer - Rio de Janeiro (RJ), Brasil. 3. Complexo Hospitalar de Niterói - Niterói (RJ), Brasil. 4. Hospital Universitário Antônio Pedro, Universidade Federal Fluminense - Nieterói (RJ), Brazil. 5. Hospital Quinta D'Or - Rio de Janeiro (RJ), Brazil. 6. Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz - Rio de Janeiro (RJ), Brasil. 7. Laboratório de Inflamação e Imunidade, Departamento de Imunologia, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro - Rio de Janeiro (RJ), Brasil. 8. Laboratório de Bioquímica de Resposta ao Estresse, Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro - Rio de Janeiro (RJ), Brasil. 9. Instituto D'Or de Pesquisa e Ensino - Rio de Janeiro (RJ), Brasil.
Abstract
OBJECTIVE: To evaluate the relationships of brain iron and heme with the inflammatory response of the systemic and central nervous systems and to investigate the role of defensive systems against the toxicity of iron and heme in the central nervous system. METHODS: We assessed a prospective cohort of patients presenting with intracerebral and subarachnoid hemorrhage. We assayed plasma and cerebrospinal fluid samples for the presence of iron, heme, hemopexin, haptoglobin, enolase, S100-β and cytokines for the first three days following hemorrhagic stroke. We also analyzed the dynamic changes in these components within both fluids and their relationship with early mortality rates. RESULTS: Hemopexin and haptoglobin concentrations were nearly negligible in the brain after intracerebral and subarachnoid hemorrhage. Cerebrospinal fluid iron and heme concentrations correlated with a pro-inflammatory response in the central nervous system, and plasmatic and cerebrospinal fluid inflammatory profiles on the third day after hemorrhagic stroke were related to early mortality rates. Interleukin 4 levels within the cerebrospinal fluid during the first 24 hours after hemorrhagic stroke were found to be higher in survivors than in non-survivors. CONCLUSION: Iron and heme are associated with a pro-inflammatory response in the central nervous system following hemorrhagic stroke, and protections against hemoglobin and heme are lacking within the human brain. Patient inflammatory profiles were associated with a poorer prognosis, and local anti-inflammatory responses appeared to have a protective role.
OBJECTIVE: To evaluate the relationships of brain iron and heme with the inflammatory response of the systemic and central nervous systems and to investigate the role of defensive systems against the toxicity of iron and heme in the central nervous system. METHODS: We assessed a prospective cohort of patients presenting with intracerebral and subarachnoid hemorrhage. We assayed plasma and cerebrospinal fluid samples for the presence of iron, heme, hemopexin, haptoglobin, enolase, S100-β and cytokines for the first three days following hemorrhagic stroke. We also analyzed the dynamic changes in these components within both fluids and their relationship with early mortality rates. RESULTS: Hemopexin and haptoglobin concentrations were nearly negligible in the brain after intracerebral and subarachnoid hemorrhage. Cerebrospinal fluid iron and heme concentrations correlated with a pro-inflammatory response in the central nervous system, and plasmatic and cerebrospinal fluid inflammatory profiles on the third day after hemorrhagic stroke were related to early mortality rates. Interleukin 4 levels within the cerebrospinal fluid during the first 24 hours after hemorrhagic stroke were found to be higher in survivors than in non-survivors. CONCLUSION: Iron and heme are associated with a pro-inflammatory response in the central nervous system following hemorrhagic stroke, and protections against hemoglobin and heme are lacking within the human brain. Patient inflammatory profiles were associated with a poorer prognosis, and local anti-inflammatory responses appeared to have a protective role.
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