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| [PMID]: | 28747460 |
| [Au] Autor: | Schallner N; Lieberum JL; Gallo D; LeBlanc RH; Fuller PM; Hanafy KA; Otterbein LE |
| [Ad] Endereço: | From the Department of Surgery (N.S., J.-L.L., D.G., L.E.O.) and Department of Neurology (R.H.L., P.M.F., K.A.H.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Department of Anesthesiology and Critical Care, Medical Center-University Freiburg, Faculty of Medicine, German |
| [Ti] Título: | Carbon Monoxide Preserves Circadian Rhythm to Reduce the Severity of Subarachnoid Hemorrhage in Mice. |
| [So] Source: | Stroke;48(9):2565-2573, 2017 09. | | [Is] ISSN: | 1524-4628 |
| [Cp] País de publicação: | United States |
| [La] Idioma: | eng |
| [Ab] Resumo: | BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) is associated with a temporal pattern of stroke incidence. We hypothesized that natural oscillations in gene expression controlling circadian rhythm affect the severity of neuronal injury. We moreover predict that heme oxygenase-1 (HO-1/ ) and its product carbon monoxide (CO) contribute to the restoration of rhythm and neuroprotection. METHODS: Murine SAH model was used where blood was injected at various time points of the circadian cycle. Readouts included circadian clock gene expression, locomotor activity, vasospasm, neuroinflammatory markers, and apoptosis. In addition, cerebrospinal fluid and peripheral blood leukocytes from SAH patients and controls were analyzed for clock gene expression. RESULTS: Significant elevations in the clock genes , , and were observed in the hippocampus, cortex, and suprachiasmatic nucleus in mice subjected to SAH at zeitgeber time (ZT) 12 when compared with ZT2. Clock gene expression amplitude correlated with basal expression of HO-1, which was also significantly greater at ZT12. SAH animals showed a significant reduction in cerebral vasospasm, neuronal apoptosis, and microglial activation at ZT12 compared with ZT2. In animals with myeloid-specific HO-1 deletion ( ), , and expression was reduced in the suprachiasmatic nucleus, which correlated with increased injury. Treatment with low-dose CO rescued mice, restored , expression, and reduced neuronal apoptosis. CONCLUSIONS: Clock gene expression regulates, in part, the severity of SAH and requires myeloid HO-1 activity to clear the erythrocyte burden and inhibit neuronal apoptosis. Exposure to CO rescues the loss of HO-1 and thus merits further investigation in patients with SAH. |
| [Mh] Termos MeSH primário: |
Monóxido de Carbono/metabolismo
Ritmo Circadiano/genética
Expressão Gênica/efeitos dos fármacos
Heme Oxigenase-1/genética
Proteínas de Membrana/genética
Hemorragia Subaracnóidea/genética
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| [Mh] Termos MeSH secundário: |
Fatores de Transcrição ARNTL/genética
Animais
Apoptose
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética
Proteínas CLOCK/genética
Líquido Cefalorraquidiano/metabolismo
Heme Oxigenase-1/metabolismo
Seres Humanos
Imuno-Histoquímica
Inflamação
Leucócitos/metabolismo
Locomoção
Proteínas de Membrana/metabolismo
Camundongos
Proteínas do Tecido Nervoso/genética
Proteínas Circadianas Period/genética
Reação em Cadeia da Polimerase em Tempo Real
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Índice de Gravidade de Doença
Núcleo Supraquiasmático/metabolismo
Vasoespasmo Intracraniano
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| [Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (ARNTL Transcription Factors); 0 (Arntl protein, mouse); 0 (Basic Helix-Loop-Helix Transcription Factors); 0 (Membrane Proteins); 0 (Nerve Tissue Proteins); 0 (Npas2 protein, mouse); 0 (PER2 protein, human); 0 (Per1 protein, mouse); 0 (Per2 protein, mouse); 0 (Period Circadian Proteins); 7U1EE4V452 (Carbon Monoxide); EC 1.14.14.18 (Heme Oxygenase-1); EC 1.14.14.18 (Hmox1 protein, mouse); EC 2.3.1.48 (CLOCK Proteins); EC 2.3.1.48 (Clock protein, mouse) |
| [Em] Mês de entrada: | 1709 |
| [Cu] Atualização por classe: | 180307 |
[Lr] Data última revisão:
| 180307 |
| [Sb] Subgrupo de revista: | IM |
| [Da] Data de entrada para processamento: | 170728 |
| [St] Status: | MEDLINE |
| [do] DOI: | 10.1161/STROKEAHA.116.016165 |
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