RESUMO
Various studies demonstrate that CD137 (TNFRSF9, 4-1BB) promotes atherosclerosis and vascular inflammation in experimental models via interactions with the CD137 ligand (CD137L). However, the exact role of CD137 in ischemic stroke remains unclear. In this study, we analyzed dynamic changes of peripheral CD137 expression on T cells in a mouse model of cerebral ischemia-middle cerebral artery occlusion (MCAO), as well as alternation of neurological function, infarct size and cerebral inflammatory status after inhibition of the CD137/CD137L pathway using an anti-CD137L monoclonal antibody. MCAO mice showed elevated surface expression of CD137 on T cells in both peripheral blood and lymphoid tissues during early cerebral ischemia. Remarkably, blockade of the CD137/CD137L pathway reduced the post-ischemic brain damage. Our findings indicate that enhanced CD137 costimulation occurs in early cerebral ischemia and promotes T cell activation, which in turn upregulates inflammatory immune response and possibly exerting deleterious effects on cerebral ischemia.
Assuntos
Ligante 4-1BB/metabolismo , Isquemia Encefálica/metabolismo , Ligante 4-1BB/sangue , Animais , Linfócitos B/metabolismo , Isquemia Encefálica/etiologia , Isquemia Encefálica/imunologia , Isquemia Encefálica/patologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Membrana Celular/metabolismo , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/patologia , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
OBJECTIVE: To investigate the effects of different factors associated with open heart surgery under cardiopulmonary bypass (CPB) on neurocognitive function. METHODS: The cognitive capacity of 50 patients undergoing open heart surgery under CPB were studied on the day before operation and the 14th day postoperatively with Basic Cognitive Capacity Test battery, including 7 subtest: Digit Discrimination, Mental Arithmetic, Chinese Character Rotation, Digit Working Memory, Dual-word recognition, Tri-digit Recognition, and Meaningless Figure Recognition. The correlation between the postoperative cognitive decline and the factors associated with CPB was analyzed. RESULTS: The total score of the Basic Cognitive Capacity Test 14 days postoperatively in 31 out of the 50 patients (62%) was 50 +/- 13, significantly lower than the preoperative score (54 +/- 10, P < 0.01), the decline being especially marked in Digit Discrimination, Digit Working Memory, and Dual-word Recognition (all P < 0.01). The postoperative decrease in cognitive function was correlated with age (P < 0.05), CPB time (P < 0.01), rewarming rate (P < 0.01), and the highest PaCO(2) (P < 0.05). CONCLUSION: The incidence of cognitive dysfunction is higher in patients undergoing open heart surgery with CPB during the early postoperative period. Shortening CPB time, slowing rewarming, and appropriately increasing the level of PaCO2 will help to degrade the possibility of cognitive dysfunction after open heart surgery.
Assuntos
Ponte Cardiopulmonar/efeitos adversos , Transtornos Cognitivos/etiologia , Adulto , China/epidemiologia , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/prevenção & controle , Feminino , Doenças das Valvas Cardíacas/cirurgia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-OperatóriasRESUMO
AIMS: Intraplaque neovascularization and foam cell infiltration contribute to the development of unstable plaque, leading to thromboembolism and stroke. Cell adhesion molecules (CAMs) have been reported to be involved in the progression of atherosclerosis and plaque vulnerability. The aim of this study was to assess the association of adhesion molecule CD146 with carotid plaque instability. METHODS: We collected forty atherosclerotic plaques from 40 patients undergoing carotid endarterectomy. The clinical information of each patient was obtained, and the plaque morphology and characteristics were examined by the ultrasound. The CD146 expressions of the plaques were graded by using semiquantitative scales. The serum level of soluble form of CD146 was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: CD146 expression was mainly on the intraplaque blood vessels and infiltrated macrophages. The CD146 expression was strongly correlated with the matrix metalloproteinase-9(MMP-9)expressions (P < 0.001) in the plaques. Soluble CD146 (sCD146) was also elevated in patients with atherosclerotic plaques. There was significant correlation between the increased CD146 expression and sCD146 level (P = 0.0057). sCD146 correlated well with serum MMP-9 (P < 0.0044), IL-6 (P = 0.0044) and high sensitivity C-reactive protein (hsCRP) (P = 0.005). CONCLUSIONS: Adhesion molecules CD146 and its soluble form strongly correlated with the development of inflammation of atherosclerosis and plaque instability. CD146 may be a promising biomarker for monitoring the development and instability of atherosclerotic plaque in patients with carotid diseases.