RESUMO
BACKGROUND: Phospholipids and sphingolipids are cell membrane components, that participate in signaling events and regulate a wide variety of vital cellular processes. Sphingolipids are involved in ischemic stroke pathophysiology. Throughout cleavage of membrane sphingomyelin by sphingomyelinase in stroke patients, it results in increased Ceramide (Cer) levels in brain tissue. Different studies showed the evidence that sphingomyelinase with Cer production induces expression of interleukin (IL)-6 and have vasoconstrictive proprieties. With this study, we intend to evaluate cerebrospinal fluid (CSF) lipid profile changes in a rabbit closed cranium subarachnoid hemorrhage (SAH) model. METHODS: A total of 14 New Zealand white rabbits were randomly allocated either to SAH or sham group. In the first group SAH was induced by extracranial-intracranial shunting from the subclavian artery into the cisterna magna. Intracranial pressure (ICP) and arterial blood pressure were continuously monitored. Digital subtraction angiography of the basilar artery, CSF and blood samples were performed at day 0 pre SAH and on day 3 post SAH. The amount of IL-6 and various lipids in CSF were quantified using ELISA and Liquid Chromatography-Mass Spectrometry respectively. Cell death was detected in bilateral basal cortex, hippocampus (CA1 and CA3) using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). RESULTS: SAH Induction led to acute increase of ICP and increased delayed cerebral vasospasm (DCVS). At follow up CSF IL-6 levels showed a significant increase compared to baseline. Between baseline and follow up there were no significant differences in any of the measured CSF Lipids irrespective of subgroups. No relevant correlation was found between IL-6 and any of the sphingolipids. We found a correlation between baseline and follow up for the phospholipids phosphatidylethanolamine and phosphatidylcholine. CONCLUSIONS: Neuronal apoptosis, DCVS and IL-6 seems not to be related to changes in CSF lipid profiles except for PEA and PC in a rabbit closed cranium SAH model.
Assuntos
Artéria Basilar/fisiopatologia , Interleucina-6/líquido cefalorraquidiano , Lipídeos/líquido cefalorraquidiano , Neurônios/metabolismo , Hemorragia Subaracnóidea/líquido cefalorraquidiano , Vasoconstrição , Vasoespasmo Intracraniano/líquido cefalorraquidiano , Animais , Apoptose , Artéria Basilar/diagnóstico por imagem , Biomarcadores/líquido cefalorraquidiano , Modelos Animais de Doenças , Interleucina-6/biossíntese , Pressão Intracraniana , Neurônios/patologia , Fosfatidilcolinas/líquido cefalorraquidiano , Fosfatidiletanolaminas/líquido cefalorraquidiano , Projetos Piloto , Coelhos , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/patologia , Hemorragia Subaracnóidea/fisiopatologia , Vasoespasmo Intracraniano/diagnóstico por imagem , Vasoespasmo Intracraniano/patologia , Vasoespasmo Intracraniano/fisiopatologiaRESUMO
BACKGROUND: More than half of subarachnoid hemorrhage (SAH) patients develop angiographically detectable delayed cerebral vasospasm (dCVS). It mostly occurs between days 4 and 15 after ictus and can be associated with neurological deficits that contribute to increased morbidity and mortality after SAH. Although dCVS is well studied, there are only a handful of reports on the acute phase of vasospasm (APV) occurring after treatment of intracranial aneurysms, whether ruptured or not. The aim of the current study is to elucidate the association of intraoperative cerebral vasospasm (iCVS) with the incidence of dCVS. METHOD: We retrospectively reviewed consecutive patients who were treated for aneurysmal SAH or incidental aneurysms during the study period. Angiograms of patients undergoing aneurysm treatment were reviewed. Spasm severity was classified with respect to reduction in the transverse diameter. Mild vasospasm was defined as a reduction in vessel diameter of 10-30 %; moderate, 30-50 %; and severe vasospasm, >50 %. Statistical significance was tested using the Χ² test with p < 0.05. Correlations between iCVS and other factors were investigated. RESULTS: Of 109 patients, 77 patients (33 men and 44 women) presented with acute SAH and 32 patients (9 men and 23 women) were treated for incidental aneurysms. Seventeen (22 %) of 77 patients presenting with acute SAH had evidence of acute (within 72 h after SAH ictus) CVS. In 16 of 17 (94.1 %) patients, this vasospasm was observed immediately after treatment and was therefore termed iCVS. Eleven (30 %) of 36 patients undergoing clipping and 5 (14 %) of 36 patients with endovascular aneurysm occlusion had iCVS (p = 0.07). Patients presenting with acute SAH had a higher incidence of iCVS than patients undergoing elective aneurysm treatment (p = 0.02). Only one patient (3 %) had iCVS in the elective treatment group whereas 16 (20 %) had iCVS after SAH. The incidence of dCVS, delayed ischemic neurological deficits (DNDs), and poor outcome in patients presenting with iCVS during surgical treatment of ruptured aneurysms was 56 % (p = 0.001), 63 % (p = 0.02), and 38 % (p = 0.14), respectively. CONCLUSION: APV exists and is a common finding in patients with SAH. Further studies are warranted to correlate the presence of APV with postoperative ischemia, dCVS, and outcome.
Assuntos
Isquemia Encefálica/epidemiologia , Hemorragia Subaracnóidea/epidemiologia , Hemorragia Subaracnóidea/terapia , Vasoespasmo Intracraniano/epidemiologia , Doença Aguda , Idoso , Isquemia Encefálica/diagnóstico por imagem , Angiografia Cerebral , Embolização Terapêutica , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Retrospectivos , Índice de Gravidade de Doença , Hemorragia Subaracnóidea/diagnóstico por imagem , Vasoespasmo Intracraniano/diagnóstico por imagemRESUMO
BACKGROUND: In subarachnoid hemorrhage (SAH), occurrence of cerebral vasospasm (CVS) mediated by endothelin (ET)-1 might be a result of a compartmental inflammatory response with interleukin (IL)-6 release. We aim to investigate the relationship between ET-1 and IL-6 in association of CVS. METHODS: A total of 24 New Zealand white rabbits where randomly allocated into 3 groups: SAH (N.=10), IL-6 (N.=10), and sham (N.=4). SAH was induced by a closed cranium extracranial-intracranial shunt model. In the IL-6 group, IL-6 was injected into the cisterna magna. CVS of the basilar artery was assessed by digital subtraction angiography. IL-6 and ET-1 concentrations were measured using enzyme-linked immunosorbent assay. Neuronal damage was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling. RESULTS: A significant increase between baseline (day 0) and follow-up (day 3) was found in CSF IL-6 levels of animals in the SAH and IL-6 group. There was a statistically significant correlation between IL-6 and ET-1 levels in the CSF (Pearson's r=0.454, P=0.003). CVS at day 3 was more pronounced in the SAH than in the IL-6 group: 26.0 ±7.2 % and 16.7 ±5.0 % respectively. TUNEL positive apoptotic neurons in the hippocampal formation were present in the SAH group and in a lesser degree in the IL-6 group. CONCLUSIONS: The results indicate that IL-6 triggered CVS after SAH is ET-1 dependent. IL-6 may be a target for new therapeutic approaches.