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1.
J Stroke Cerebrovasc Dis ; 33(4): 107591, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38266691

RESUMO

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is known to be triggered by several specific human activities. Sleep, by contrast, has not been considered a triggering activity for aSAH, and clinical characteristics of patients who sustain aSAH during sleep have rarely been reported in the literature. METHODS: This is a retrospective analysis on the data acquired through a multicenter aSAH registry. Between January 2019 and December 2021, a total of 732 aSAH patients had been registered into our database. After excluding 109 patients whose activities at aSAH onset had been unidentifiable, the remaining 623 aSAH patients were dichotomized to 59 patients who sustained aSAH during sleep (Sleep group) and 564 patients who sustained aSAH during daytime activities (Awake group). Two-group comparison of demographic variables and multivariate logistic regression analysis were performed to clarify their clinical characteristics and identify potential risk factors. RESULTS: The Sleep group exhibited significantly higher frequencies of diabetes (15.5 % vs. 6.4 %, p = 0.01) and antiplatelet use (13.8 % vs. 4.6 %, p=0.004) than the Awake group. Furthermore, multivariate logistic regression analysis showed that diabetes (OR, 3.051; 95 % CI, 1.281-7.268; p = 0.012) and antiplatelet use (OR, 3.640; 95 % CI, 1.422-9.316; p = 0.007) were correlated with aSAH occurring during sleep. There were no significant inter-group differences in the patient outcomes evaluated at discharge. CONCLUSION: The current results indicate that risk factors may exist for aSAH occurring during sleep. Further investigations on how comorbidities such as diabetes, antiplatelet use and sleep apnea affect human hemodynamic and hemostatic parameters during sleep is warranted to better understand those relationships.


Assuntos
Diabetes Mellitus , Hemorragia Subaracnóidea , Humanos , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Sono , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/epidemiologia , Hemorragia Subaracnóidea/etiologia , Estudos Multicêntricos como Assunto
2.
Eur Neurol ; 84(2): 119-123, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33780954

RESUMO

BACKGROUND: Patients with moyamoya disease often develop cerebral infarction and hemorrhage, but the ischemic and hemorrhagic subtypes are difficult to diagnose prior to disease onset. We aimed to differentiate the ischemic and hemorrhagic subtypes of moyamoya disease by analyzing the intralateral and perilateral ventricular arteries on the original axial magnetic resonance angiography (MRA) images. METHODS: We retrospectively analyzed the intralateral and perilateral ventricular arteries on the original axial time-of-flight (TOF)-MRA images of 18 patients with hemorrhagic moyamoya disease, 25 patients with ischemic moyamoya disease, and 22 control patients with unruptured aneurysms. RESULTS: There were significantly more intralateral and perilateral ventricular arteries on the original axial MRA images in the patients with hemorrhagic moyamoya disease (6.3 ± 2.7) than in those with ischemic moyamoya disease (0.8 ± 0.9) and those with unruptured aneurysms (0.4 ± 0.8). CONCLUSION: The intralateral and perilateral ventricular arteries on the original axial TOF-MRA images might suggest the hemorrhagic type of moyamoya disease prior to onset.


Assuntos
Doença de Moyamoya , Adulto , Artérias , Humanos , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Doença de Moyamoya/diagnóstico por imagem , Estudos Retrospectivos
3.
Microcirculation ; 28(4): e12685, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33586295

RESUMO

OBJECTIVE: The present study developed an image-based analysis method that uses indocyanine green videoangiography (ICG-VA) to measure flow velocity in the arteries and veins of the cortical surface in patients undergoing neurosurgery. METHODS: MATLAB-based code was used to correct motion artifacts in the ICG-VA and determine the time-intensity curve of the ICG. The slope of the initial increase in ICG intensity following the bolus injection was measured and normalized using the predicted input function in the imaging field. Flow velocity over a certain distance determined by the user was measured based on a time shift of the time-intensity curves along the centerline of the vessels. RESULTS: The normalized slope of ICG intensity represented the expected differences in the flow velocity among the artery (0.67 ± 0.05 s-1 ), parenchymal tissue (0.49 ± 0.10 s-1 ), and vein (0.44 ± 0.11 s-1 ). The flow velocities measured along the vessel centerline were 2.5 ± 1.1 cm/s and 1.1 ± 0.3 cm/s in the arteries (0.5 ± 0.2 mm in diameter) and veins (0.6 ± 0.2 mm in diameter), respectively. CONCLUSIONS: An image-based analysis method for ICG-VA was developed to map the expected differences in the flow velocity based on the rising slope of ICG intensity and to measure the absolute flow velocities using the flexible zone and cross-correlation methods.


Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Angiografia Cerebral , Verde de Indocianina , Aneurisma Intracraniano/diagnóstico por imagem , Velocidade do Fluxo Sanguíneo , Circulação Cerebrovascular , Angiofluoresceinografia , Humanos
4.
J Clin Neurosci ; 75: 206-209, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32204956

RESUMO

Ultrasonography (US) has been used as a reliable imaging modality, providing real-time information during neurosurgical operations. One recent innovative US technique, superb microvascular imaging (SMI), visualizes small vessels and flow, which are not detected with standard US with doppler. We apply SMI to intraoperative US monitoring in emergency surgery for intracerebral hemorrhage (ICH). Eleven consecutive patients with ICH underwent endoscopic emergency surgery under US monitoring with SMI. After performing a small craniotomy, US images were obtained using SMI, a fusion technique, and a contrast agent technique, with the probe on the brain surface during surgery. Fusion images were obtained with the probe on the head before craniotomy in some patients. Animated US images with SMI could differentiate hematoma containing no vessels from brain tissue, and flow images using SMI and contrast agent techniques clarified the borderlines. Animated fusion images of intraoperative US and preoperative CT provided information on the extent of hematoma and residual hematoma during emergency surgery. We made various fusion CT images showing intracranial hematoma with US probes and decided on the skin incision line before beginning surgery, as if we were using a neuronavigation system. US with SMI, contrast agent, and fusion techniques provide information on the extent of intracranial hematoma and residual hematoma with no vessels and no flow. Monitoring by US and fusion CT images is useful for ICH surgery as a next-generation neuronavigator.


Assuntos
Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/cirurgia , Microvasos/diagnóstico por imagem , Microvasos/cirurgia , Monitorização Intraoperatória/métodos , Ultrassonografia de Intervenção/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Craniotomia/métodos , Tratamento de Emergência/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuronavegação/métodos
5.
World Neurosurg ; 106: 1057.e1-1057.e7, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28755914

RESUMO

BACKGROUND: Intraoperative monitoring of cochlear nerve action potential (CNAP) has been used in patients with small vestibular schwannoma (<15 mm) to preserve cochlear nerve function. We performed surgery for a larger vestibular schwannoma under CNAP monitoring with the aim of preserving cochlear nerve function, and compared the data with findings from 10 patients with hemifacial spasm who underwent microvascular decompression surgery. CASE DESCRIPTION: We report the case of a patient with a 26-mm vestibular schwannoma and normal hearing function who underwent neurosurgery under electrophysiological monitoring of the facial and cochlear nerves. Amplitudes of evoked facial muscle responses were maintained at approximately 70% during the operation. The latency of wave V on brainstem auditory evoked potential (BAEP) increased by 0.5 ms, and amplitude was maintained at approximately 70% of the value at the beginning of the operation. Latencies of P1, N1, and P2 on CNAP did not change intraoperatively. These latencies were comparable to those of 10 normal patients with hemifacial spasm. CNAP monitoring proved very useful in confirming the location of the cochlear nerve in the operative field and preserving cochlear nerve function. Both facial nerve function and hearing acuity were completely preserved after tumor removal, and wave V latency on BAEP returned to normal and was maintained in the normal range for at least 2 years. CONCLUSIONS: CNAP monitoring is extremely useful for preserving the function of the unseen cochlear nerve during vestibular schwannoma surgery.


Assuntos
Cóclea/cirurgia , Nervo Coclear/cirurgia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Audição/fisiologia , Neuroma Acústico/cirurgia , Humanos , Masculino , Cirurgia de Descompressão Microvascular/métodos , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Neuroma Acústico/diagnóstico , Neuroma Acústico/fisiopatologia , Procedimentos Neurocirúrgicos/métodos
6.
J Neurol Sci ; 373: 201-207, 2017 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-28131187

RESUMO

OBJECTIVE: In patients with severe steno-occlusive disease of a main cerebral artery, decreased cerebrovascular reserve (CVR) and cognitive impairment without causative focal lesions on magnetic resonance imaging have been reported. We examined ipsilateral and contralateral CVR and cognition before and after superficial temporal artery-middle cerebral artery (MCA) anastomosis operation in patients with internal carotid artery (ICA) or MCA occlusion. METHODS: In 30 patients with ICA or MCA occlusion, cognitive impairment, and decreased CVR, we examined cognition, CVR, leukoaraiosis grades, and blood data. Data from 15 patients who underwent anastomosis were compared to that in 15 patients who did not undergo anastomosis, and to bilateral data already reported on 65 patients with severe steno-occlusive disease. RESULTS: Cerebral blood flow, CVR, and cognition improved after anastomosis compared to before, and compared to patients without anastomosis; improved values were maintained for 5years. CVR recovered after anastomosis, matching the linear relationship between ipsilateral and contralateral CVR seen in the 65 patients. CONCLUSION: The postoperative improvement in cognition and synchronized recovery on the regression line between CVR of the ipsilateral occlusion and contralateral sides may suggest that the CVR is widespread and nonselectively related to cognitive function.


Assuntos
Estenose das Carótidas/cirurgia , Revascularização Cerebral , Disfunção Cognitiva/cirurgia , Infarto da Artéria Cerebral Média/cirurgia , Artéria Cerebral Média/cirurgia , Artérias Temporais/cirurgia , Idoso , Anastomose Cirúrgica , Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/fisiopatologia , Estenose das Carótidas/complicações , Estenose das Carótidas/fisiopatologia , Estenose das Carótidas/psicologia , Circulação Cerebrovascular , Cognição/fisiologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Feminino , Humanos , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/fisiopatologia , Infarto da Artéria Cerebral Média/psicologia , Modelos Lineares , Masculino , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/fisiopatologia , Testes Neuropsicológicos , Recuperação de Função Fisiológica , Artérias Temporais/diagnóstico por imagem , Artérias Temporais/fisiopatologia , Tomografia Computadorizada de Emissão de Fóton Único , Resultado do Tratamento
7.
BMC Med Ethics ; 15: 33, 2014 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-24758583

RESUMO

BACKGROUND: A challenge in human genome research is how to describe the populations being studied. The use of improper and/or imprecise terms has the potential to both generate and reinforce prejudices and to diminish the clinical value of the research. The issue of population descriptors has not attracted enough academic attention outside North America and Europe. In January 2012, we held a two-day workshop, the first of its kind in Japan, to engage in interdisciplinary dialogue between scholars in the humanities, social sciences, medical sciences, and genetics to begin an ongoing discussion of the social and ethical issues associated with population descriptors. DISCUSSION: Through the interdisciplinary dialogue, we confirmed that the issue of race, ethnicity and genetic research has not been extensively discussed in certain Asian communities and other regions. We have found, for example, the continued use of the problematic term, "Mongoloid" or continental terms such as "European," "African," and "Asian," as population descriptors in genetic studies. We, therefore, introduce guidelines for reporting human genetic studies aimed at scientists and researchers in these regions. CONCLUSION: We need to anticipate the various potential social and ethical problems entailed in population descriptors. Scientists have a social responsibility to convey their research findings outside of their communities as accurately as possible, and to consider how the public may perceive and respond to the descriptors that appear in research papers and media articles.


Assuntos
Pesquisa Biomédica , Etnicidade/genética , Pesquisa em Genética/ética , Projeto Genoma Humano , Comunicação Interdisciplinar , Grupos Raciais/genética , Relatório de Pesquisa/normas , Pesquisa Biomédica/ética , Feminino , Guias como Assunto , Projeto Genoma Humano/ética , Humanos , Japão , Masculino , Preconceito , Grupos Raciais/etnologia , Pesquisadores/ética , Terminologia como Assunto
8.
Exp Transl Stroke Med ; 3: 15, 2011 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-22087550

RESUMO

BACKGROUND: Angiotensin II type 1 receptor (AT1R) blockers lower the incidence of ischemic stroke in hypertensive patients and attenuate brain inflammation and injury in animal models. Although AT1R on both blood cells (BC) and vascular endothelial cells (EC) can be activated by angiotensin II (Ang II) to elicit inflammation, little is known about the relative contributions of AT1R expressed on BC and EC to the brain injury responses to ischemia and reperfusion (I/R) in the setting of angiotensin-induced hypertension. METHODS: The contributions of BC- and EC-associated AT1R to I/R-induced brain inflammation and injury were evaluated using wild type (WT), AT1aR-/-, and bone marrow chimera mice with either a BC+/EC+ (WT→WT) or BC-/EC+ (AT1aR-/-→WT) distribution of AT1aR. The adhesion of leukocytes and platelets in venules, blood brain barrier (BBB) permeability and infarct volume were monitored in postischemic brain of normotensive and Ang II-induced hypertensive mice. RESULTS: The inflammatory (blood cell adhesion) and injury (BBB permeability, infarct volume) responses were greatly exaggerated in the presence of Ang II-induced hypertension. The Ang II-enhanced responses were significantly blunted in AT1aR-/- mice. A similar level of protection was noted in AT1aR-/- →WT mice for BBB permeability and infarct volume, while less or no protection was evident for leukocyte and platelet adhesion, respectively. CONCLUSIONS: BC- and EC-associated AT1aR are both involved in the brain injury responses to ischemic stroke during Ang II-hypertension, with EC AT1aR contributing more to the blood cell recruitment response and BC AT1aR exerting a significant influence on the BBB disruption and tissue necrosis elicited by I/R.

9.
Microcirculation ; 17(8): 641-9, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21044218

RESUMO

Angiotensin II (AngII) and AngII type-1 receptors (AT1r) have been implicated in the pathogenesis of hypertension and ischemic stroke. The objectives of this study was to determine if/how chronic AngII administration affects blood-brain barrier (BBB) function and blood cell adhesion in the cerebral microvasculature. AngII-loaded osmotic pumps were implanted in wild type (WT) and mutant mice. Leukocyte and platelet adhesion were monitored in cerebral venules by intravital microscopy and BBB permeability detected by Evans blue leakage. AngII (two week) infusion increased blood pressure in WT mice. This was accompanied by an increased BBB permeability and a high density of adherent leukocytes and platelets. AT1r (on the vessel wall, but not on blood cells) was largely responsible for the microvascular responses to AngII. Immunodeficient (Rag-1(-/-) ) mice exhibited blunted blood cell recruitment responses without a change in BBB permeability. A similar protection pattern was noted in RANTES(-/-) and P-selectin(-/-) mice, with bone marrow chimeras (blood cell deficiency only) yielding responses comparable to the respective knockouts. These findings implicate AT1r in the microvascular dysfunction associated with AngII-induced hypertension and suggest that immune cells and blood cell-associated RANTES and P-selectin contribute to the blood cell recruitment, but not the BBB failure, elicited by AngII.


Assuntos
Angiotensina II/fisiologia , Hipertensão/fisiopatologia , Angiotensina II/administração & dosagem , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/fisiologia , Adesão Celular , Circulação Cerebrovascular/efeitos dos fármacos , Circulação Cerebrovascular/fisiologia , Quimiocina CCL5/deficiência , Quimiocina CCL5/genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/fisiologia , Hipertensão/sangue , Hipertensão/etiologia , Hipertensão/patologia , Leucócitos/patologia , Leucócitos/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia de Vídeo , Microvasos/patologia , Microvasos/fisiopatologia , Selectina-P/genética , Selectina-P/fisiologia , Adesividade Plaquetária , Receptor Tipo 1 de Angiotensina/fisiologia , Sistema Renina-Angiotensina/fisiologia , Linfócitos T/patologia , Linfócitos T/fisiologia , Quimeras de Transplante
10.
Stroke ; 41(1): 147-52, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19892996

RESUMO

BACKGROUND AND PURPOSE: Increased blood-brain barrier (BBB) permeability, brain edema, and hemorrhage are important consequences of cerebral venous sinus thrombosis (CVST). The objective of this study was to define the role of the protein C pathway in the BBB permeability and edema elicited by experimental CVST. The role of neutrophil recruitment was also evaluated. METHODS: Edema, BBB permeability, leukocyte-endothelial cell adhesion (LECA) and inflammatory cytokine levels were monitored in a murine model of CVST. The role of activated protein C (APC) was assessed in wild type mice (WT) receiving APC neutralizing antibody and in endothelial protein C receptor overexpressing mice (EPCR-tg). Neutrophil involvement was evaluated using an anti-CD18 antibody (Ab) and antineutrophil serum. RESULTS: Brain edema and increases in BBB permeability and LECA were noted 48 hours after CVST. APC immunoblockade exacerbated these responses, while EPCR-tg exhibited blunted responses, as did WT treated with either antineutrophil serum or the CD18 Ab. CONCLUSIONS: The protein C pathway protects the brain against the deleterious microvascular responses to CVST, a response that appears to be linked to the recruitment of inflammatory cells.


Assuntos
Edema Encefálico/enzimologia , Mediadores da Inflamação/fisiologia , Proteína C/metabolismo , Transdução de Sinais/fisiologia , Trombose dos Seios Intracranianos/enzimologia , Animais , Barreira Hematoencefálica/enzimologia , Barreira Hematoencefálica/patologia , Edema Encefálico/etiologia , Edema Encefálico/fisiopatologia , Cavidades Cranianas/enzimologia , Cavidades Cranianas/patologia , Ativação Enzimática/fisiologia , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Infiltração de Neutrófilos/fisiologia , Proteína C/fisiologia , Trombose dos Seios Intracranianos/complicações , Trombose dos Seios Intracranianos/fisiopatologia
11.
J Cereb Blood Flow Metab ; 29(4): 759-70, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19209180

RESUMO

Chronic stroke is a highly important but under-investigated scientific problem in neurologic research. We have reported earlier that stem cell factor (SCF) in combination with granulocyte-colony stimulating factor (G-CSF) treatment during chronic stroke improves functional outcomes. Here we have determined the contribution of bone marrow-derived cells in angiogenesis and neurogenesis, which are enhanced by SCF+G-CSF treatment during chronic stroke. Using bone marrow tracking, flow cytometry, 2-photon live brain imaging, and immunohistochemistry, we observed that the levels of circulating bone marrow stem cells (BMSCs) (CD34+/c-kit+) were significantly increased by SCF+G-CSF treatment. In addition, live brain imaging revealed that numerous bone marrow-derived cells migrate into the brain parenchyma in the treated mice. We also found that bone marrow-derived cells, bone marrow-derived endothelial cells, vascular density, and bone marrow-derived neurons were significantly augmented by SCF+G-CSF. It is interesting that, in addition to the increase in bone marrow-derived endothelial cells, the number of bone marrow-derived pericytes was reduced after SCF+G-CSF treatment during chronic stroke. These data suggest that SCF+G-CSF treatment can enhance repair of brain damage during chronic stroke by mobilizing BMSCs, and promoting the contribution of bone marrow-derived cells to angiogenesis and neurogenesis.


Assuntos
Encéfalo/fisiologia , Fator Estimulador de Colônias de Granulócitos/fisiologia , Neurogênese/fisiologia , Regeneração/fisiologia , Fator de Células-Tronco/fisiologia , Acidente Vascular Cerebral/patologia , Animais , Células da Medula Óssea , Encéfalo/patologia , Circulação Cerebrovascular , Doença Crônica , Camundongos , Neovascularização Fisiológica , Células-Tronco/fisiologia
12.
Shock ; 31(3): 275-9, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18665045

RESUMO

Although clinical obesity is associated with increases in the morbidity and mortality of sepsis, little is known about the mechanisms that underlie the influence of obesity on sepsis. The objective of this study was to determine (a) whether obesity is associated with exaggerated inflammatory and thrombogenic responses in the intestinal microvasculature of septic mice and (b) whether these microvascular alterations are related to changes in the serum levels of cytokines that are produced by adipose tissue. Intravital microscopy was used to quantify leukocyte and platelet adhesion in intestinal postcapillary venules of lean wild-type (WT) mice, and two murine models of obesity, that is, ob/ob and db/db mice. Sepsis was induced by cecal ligation and perforation (CLP). Serum cytokine levels were measured using a cytometric bead assay, whereas adipokines were quantified using enzyme-linked immunosorbent assay. Cecal ligation and perforation elicited significant increases in the adhesion of leukocytes and platelets in venules of lean WT mice. These CLP-induced adhesive interactions were much more pronounced in the microvasculature of both ob/ob and db/db mice. Cecal ligation and perforation was associated with significant increases in serum cytokines in both WT and ob/ob mice, but such changes were not detected in db/db mice. However, db/db (but not WT or ob/ob) mice did exhibit significant increases in serum leptin and adiponectin levels after CLP. Sepsis promotes more intense inflammatory and thrombogenic responses in the gut microcirculation of obese mice than in their lean counterparts. The obesity-enhanced microvascular dysfunction in septic mice shows no consistent correlation with serum cytokines or adipokines.


Assuntos
Mucosa Intestinal/metabolismo , Intestinos/irrigação sanguínea , Obesidade/sangue , Sepse/sangue , Adiponectina/sangue , Animais , Plaquetas/metabolismo , Plaquetas/microbiologia , Capilares/metabolismo , Capilares/patologia , Adesão Celular , Citocinas/sangue , Humanos , Inflamação/sangue , Inflamação/patologia , Inflamação/fisiopatologia , Intestinos/patologia , Leptina/sangue , Camundongos , Camundongos Obesos , Microcirculação , Obesidade/patologia , Obesidade/fisiopatologia , Adesividade Plaquetária , Sepse/patologia , Sepse/fisiopatologia , Vênulas/metabolismo , Vênulas/patologia
13.
Stroke ; 39(9): 2560-70, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18635850

RESUMO

BACKGROUND AND PURPOSE: Although chemokines have been implicated in cardiovascular diseases, few studies have addressed the role of these inflammatory mediators in ischemic stroke. This study tested the hypothesis that RANTES (CCL5; regulated on activation, normal T-cell expressed and secreted) mediates the cerebral microvascular dysfunction, inflammation, and tissue injury induced by brain ischemia and reperfusion. METHODS: After 60-minute middle cerebral artery occlusion and reperfusion, the adhesion of leukocytes and platelets in cerebral venules, infarct volume, and blood-brain barrier permeability were measured in wild-type mice (WT), RANTES-deficient mice (RANTES(-/-)), WT mice transplanted with RANTES(-/-) bone marrow (RANTES>WT), and control bone marrow chimeras (WT>WT). The concentration of RANTES and several cytokines was also measured by enzyme-linked immunosorbent assay and a cytometric bead array. RESULTS: The enhanced leukocyte and platelet adhesion, increased blood-brain barrier permeability, and tissue infarction elicited in WT and WT>WT mice after middle cerebral artery occlusion and reperfusion were significantly blunted in RANTES(-/-) mice. Similar attenuation of the middle cerebral artery occlusion and reperfusion-induced responses were noted in RANTES>WT chimeras. Although RANTES deficiency did not alter the changes in tissue cytokine levels elicited by middle cerebral artery occlusion and reperfusion, plasma concentrations interleukin-6, interleukin-10, and interleukin-12 were all reduced. CONCLUSIONS: These findings implicate blood cell-derived RANTES in the microvascular, inflammatory, and tissue injury responses of the brain to ischemia and reperfusion.


Assuntos
Infarto Encefálico/sangue , Isquemia Encefálica/sangue , Quimiocina CCL5/genética , Quimiocina CCL5/metabolismo , Encefalite/sangue , Traumatismo por Reperfusão/sangue , Animais , Células Sanguíneas/metabolismo , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/fisiopatologia , Infarto Encefálico/genética , Infarto Encefálico/fisiopatologia , Isquemia Encefálica/genética , Isquemia Encefálica/fisiopatologia , Modelos Animais de Doenças , Encefalite/genética , Encefalite/fisiopatologia , Infarto da Artéria Cerebral Média/sangue , Infarto da Artéria Cerebral Média/genética , Infarto da Artéria Cerebral Média/fisiopatologia , Interleucinas/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microcirculação/fisiologia , Adesividade Plaquetária/fisiologia , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/fisiopatologia
14.
Stroke ; 39(3): 943-50, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18239178

RESUMO

BACKGROUND AND PURPOSE: Although epidemiological studies reveal an increased incidence of obesity and an association between obesity and the prevalence/severity of ischemic stroke, little is known about the mechanisms that link obesity to ischemic stroke. This study tested the hypothesis that obesity exacerbates the cerebrovascular dysfunction and tissue injury induced by brain ischemia and reperfusion. METHODS: The adhesion of leukocytes and platelets in cerebral venules, blood-brain barrier permeability, brain water content, and infarct volume were measured in wild-type, obese (ob/ob), and leptin-reconstituted ob/ob mice subjected to 30 minutes middle cerebral artery occlusion and reperfusion. Tissue and plasma cytokine levels were determined by cytometric bead array, and a role for monocyte chemoattractant protein-1 and interleukin-6 was assessed using blocking antibodies. RESULTS: Compared with wild-type mice, ob/ob exhibited larger increases in leukocyte and platelet adhesion, blood-brain barrier permeability, water content, and infarct volume after middle cerebral artery occlusion-reperfusion. Reconstitution of leptin in ob/ob mice tended to further enhance all reperfusion-induced responses. Ob/ob mice also exhibited higher plasma levels of monocyte chemoattractant protein-1 and interleukin-6 than wild-type mice. Immunoneutralization of monocyte chemoattractant protein-1, but not interleukin-6, reduced infarct volume in ob/ob mice. CONCLUSIONS: Obesity worsens the inflammatory and injury responses to middle cerebral artery occlusion and reperfusion by a mechanism independent of leptin deficiency. monocyte chemoattractant protein-1 appears to contribute to the exaggerated responses to ischemic stroke in obese mice.


Assuntos
Isquemia Encefálica/complicações , Quimiocina CCL2/metabolismo , Encefalite/etiologia , Obesidade/complicações , Traumatismo por Reperfusão/complicações , Acidente Vascular Cerebral/complicações , Animais , Barreira Hematoencefálica , Isquemia Encefálica/fisiopatologia , Permeabilidade Capilar , Adesão Celular , Infarto Cerebral/etiologia , Infarto Cerebral/patologia , Circulação Cerebrovascular , Quimiocina CCL2/sangue , Encefalite/fisiopatologia , Infarto da Artéria Cerebral Média/complicações , Interleucina-6/sangue , Leptina/farmacologia , Leucócitos , Masculino , Camundongos , Camundongos Obesos , Obesidade/fisiopatologia , Adesividade Plaquetária , Traumatismo por Reperfusão/fisiopatologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia
15.
Am J Physiol Heart Circ Physiol ; 292(5): H2306-15, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17220190

RESUMO

Angiotensin II type 1 (AT(1)) receptor signaling has been implicated in cerebral microvascular alterations associated with ischemia, diabetes mellitus, hypercholesterolemia, and atherosclerosis. Platelets, which express AT(1) receptors, also appear to contribute to the thrombogenic and inflammatory responses that are elicited by these pathological conditions. This study assesses the role of AT(1) receptor activation on platelet-leukocyte-endothelial cell interactions elicited in cerebral microvasculature by ischemia and reperfusion. Intravital microscopy was used to monitor the adhesion of platelets and leukocytes that were labeled with different fluorochromes, whereas dihydrorhodamine-123 was used to quantify oxygen radical production in cerebral surface of mice that were either treated with the AT(1) receptor agonist Val-angiotensin II (ANG II) or subjected to bilateral common carotid artery occlusion (BCCAO) followed by reperfusion. ANG II elicited a dose- and time- dependent increase in platelet-leukocyte-endothelial cell interactions in cerebral venules that included rolling platelets, adherent platelets on the leukocytes and the endothelial cells, rolling leukocytes, and adherent leukocytes. All of these interactions were attenuated by treatment with either P-selectin or P-selectin glycoprotein ligand 1 (PSGL-1) antibody. The AT(1) receptor antagonist candesartan and losartan as well as diphenyleneiodonium, an inhibitor of flavoproteins including NAD(P)H oxidase, significantly reduced the platelet-leukocyte-endothelial cell interactions elicited by either ANG II administration or BCCAO/reperfusion. The increased oxygen radical generation elicited by BCCAO/reperfusion was also attenuated by candesartan. These findings are consistent with an AT(1) receptor signaling mechanism, which involves oxygen radical production and ultimately results in P-selectin- and PSGL-1-mediated platelet-leukocyte-endothelial cell interactions in the cerebral microcirculation.


Assuntos
Plaquetas/fisiologia , Comunicação Celular/fisiologia , Circulação Cerebrovascular/fisiologia , Células Endoteliais/fisiologia , Leucócitos/fisiologia , Microcirculação/fisiologia , Receptor Tipo 1 de Angiotensina/metabolismo , Animais , Plaquetas/citologia , Células Cultivadas , Células Endoteliais/citologia , Leucócitos/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microcirculação/citologia
16.
J Neurol Sci ; 194(1): 59-69, 2002 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-11809168

RESUMO

The mechanism of cerebral infarction, in which thrombus formation and platelet-endothelium interaction play an important part, have not yet been clearly elucidated in vivo. The aim of this study was to observe rolling and adherent platelets and to analyze adherent leukocytes and vessel diameter change in vivo using a photothrombotic vessel occlusion model.A photothrombosis, which is mediated by free radicals, was induced in male Wistar rats in the presence of a photosensitizing dye (Photofrin II) and exposure to a filtered light. Rhodamine 6G-labeled platelets and leukocytes were visualized with intravital fluorescence videomicroscopy through a closed cranial or spinal window. The vessel diameter, photothrombosis and leukocyte adhesion were analyzed. Rolling and adherent platelets were observed during irradiation through the cerebral and spinal window. Before the platelets were recognized, the irradiated arteriole dilated significantly. After the photochemical occlusion of an arteriole, other arterioles also dilated and the adherent leukocytes increased in the venules. The photothrombosis were almost completely composed of platelets according to electron microscopic analysis. The arteriolar dilation rate and the number of adherent leukocytes in the cerebrum were greater than those in the spinal cord. By combining the photochemical thrombus formation and the fluorescence microscope techniques, we were able for the first time to observe rolling and adherent platelets and microvascular responses during photothrombosis in the cerebral and spinal microvasculature. It is suggested that free radicals, which can lead to platelet aggregation, play an important role as a cerebral vasodilator. This model is useful for cerebral and spinal microcirculatory analysis to investigate the platelet-endothelium interaction, the platelet aggregation and the effect of free radicals on cerebral and spinal microcirculation.


Assuntos
Arteríolas/fisiopatologia , Adesividade Plaquetária , Medula Espinal/irrigação sanguínea , Telencéfalo/irrigação sanguínea , Trombose/fisiopatologia , Vasodilatação , Animais , Plaquetas/patologia , Plaquetas/ultraestrutura , Adesão Celular/fisiologia , Cultura em Câmaras de Difusão , Éter de Diematoporfirina , Modelos Animais de Doenças , Progressão da Doença , Endotélio Vascular/ultraestrutura , Trombose Intracraniana/induzido quimicamente , Trombose Intracraniana/patologia , Trombose Intracraniana/fisiopatologia , Leucócitos/fisiologia , Fotocoagulação , Masculino , Microcirculação/fisiopatologia , Ratos , Ratos Wistar , Trombose/induzido quimicamente , Trombose/patologia , Vênulas/fisiopatologia
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