RESUMO
Brain injuries are often associated with intensive care admissions, and carry high morbidity and mortality rates. Ischemic stroke is one of the most frequent causes of injury to the central nervous system. It is now increasingly clear that human stroke causes multi-organ systemic disease. Brain inflammation may lead to opposing local and systemic effects. Suppression of systemic immunity by the nervous system could protect the brain from additional inflammatory damage; however, it may increase the susceptibility to infection. Pneumonia and urinary tract infection are the most common complications occurring in patients after stroke. The mechanisms involved in lung-brain interactions are still unknown, but some studies have suggested that inhibition of the cholinergic anti-inflammatory pathway and release of glucocorticoids, catecholamines, and damage-associated molecular patterns (DAMPs) are among the pathophysiological mechanisms involved in communication from the ischemic brain to the lungs after stroke. This review describes the modifications in local and systemic immunity that occur after stroke, outlines mechanisms of stroke-induced immunosuppression and their role in pneumonia, and highlights potential therapeutic targets to reduce post-stroke complications. Despite significant advances towards a better understanding of the pathophysiology of ischemic stroke-induced immunosuppression and stroke-associated pneumonia (SAP) in recent years, many unanswered questions remain. The true incidence and outcomes of SAP, especially in intensive care unit settings, have yet to be determined, as has the full extent of stroke-induced immunosuppression and its clinical implications.
Assuntos
Isquemia Encefálica/imunologia , Isquemia Encefálica/terapia , Imunomodulação/fisiologia , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/terapia , Lesões Encefálicas/imunologia , Lesões Encefálicas/fisiopatologia , Lesões Encefálicas/terapia , Isquemia Encefálica/fisiopatologia , Humanos , Imunossupressores/uso terapêutico , Pneumonia/imunologia , Pneumonia/fisiopatologia , Pneumonia/terapia , Acidente Vascular Cerebral/fisiopatologiaRESUMO
Injectable bone substitutes and techniques have been developed for use in minimally invasive procedures for bone augmentation. Objective : To develop a novel injectable thermo-sensitive alginate hydrogel (TSAH) as a scaffold to induce bone regeneration, using a minimally invasive tunnelling technique. Material and Methods : An injectable TSAH was prepared from a copolymer solution of 8.0 wt% Poly(N-isopropylacrylamide) (PNIPAAm) and 8.0 wt% AAlg-g-PNIPAAm. In vitro properties of the material, such as its microstructure and the sustained release of recombinant human bone morphogenetic protein-2 (rhBMP-2), were investigated. Then, with the subperiosteal tunnelling technique, this material, carrying rhBMP-2, was injected under the labial periosteum of the maxillary anterior alveolar ridge in a rabbit model. New bone formation was evaluated by means of X-ray, micro-computed tomography (micro-CT), fluorescence labelling, histological study, and immunohistochemistry study. Results : The material exhibited good injectability and thermo-irreversible properties. SEM showed an interconnected porous microstructure of the TSAH. The result of ALP activity indicated sustained delivery of BMP-2 from the TSAH from days 3 to 15. In a rabbit model, both TSAH and TSAH/rhBMP-2 induced alveolar ridge augmentation. The percentage of mineralised tissue in the TSAH/rhBMP-2 group (41.6±3.79%) was significantly higher than in the TSAH group (31.3±7.21%; p<0.05). The density of the regenerating tissue was higher in the TSAH/rhBMP-2 group than in the other groups (TSAH group, positive control, blank control; p<0.05). Conclusions : The TSAH provided convenient handling properties for clinical application. To some extent, TSAH could induce ridge augmentation and mineral deposition, which can be enhanced when combined with rhBMP-2 for a minimally invasive tunnelling injection. .
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Lesões Encefálicas/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Receptores de Interleucina-1/antagonistas & inibidores , Lesões Encefálicas/imunologia , Lesões Encefálicas/patologia , Encéfalo/imunologia , Encéfalo/patologia , Citocinas/análise , Citocinas/imunologia , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Receptores de Interleucina-1/imunologia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêuticoRESUMO
BACKGROUND: Cytokines have been shown to be involved in traumatic brain injury (TBI). We investigated the independent association between serum levels of IL-10 and TNF-α and hospital mortality of patients with severe TBI. METHODS: Serum IL-10 and TNF-α levels were determined after a median period (interquartile range (IQ) 25-75) of 10 h (IQ 5-18) after severe TBI in 93 consecutive patients and in randomly selected patients with mild (n = 18) and moderate (n = 16) TBI. In patients with severe TBI, additional blood samples were analyzed 30 h (IQ 22-37) and 68 h (IQ 55-78) after TBI. Age, gender, computed tomography findings, Glasgow Coma Scale score (GCS) and pupil reactions at admission, associated trauma and hospital mortality were collected. RESULTS: Elevated serum levels of IL-10, but not TNF-α, correlated significantly with GCS severity (R(2) coefficient, p < 0.0001) and were found to be associated with hospital mortality in patients with severe TBI. Elevated IL-10 remained associated with mortality (p = 0.01) in a subset of patients with isolated severe TBI (n = 74). Multiple logistic regression analysis showed that higher IL-10 levels (>90 pg/ml) at 10 or 30 h after TBI were 6 times (odds ratio (OR) 6.2, 95% confidence interval (CI) 1.2-25.1, p = 0.03) and 5 times (OR 5.4, 95% CI 1.2-25.1, p = 0.03), respectively, more frequently associated with hospital mortality than lower levels (<50 pg/ml), independently of age, GCS as well as pupil reactions at admission and associated trauma. CONCLUSIONS: Serum IL-10 levels may be a useful marker for severe TBI prognosis.
Assuntos
Lesões Encefálicas/diagnóstico , Lesões Encefálicas/imunologia , Escala de Coma de Glasgow , Escala de Gravidade do Ferimento , Interleucina-10/biossíntese , Regulação para Cima/imunologia , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Lesões Encefálicas/sangue , Feminino , Humanos , Interleucina-10/sangue , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Traumatic brain injury (TBI) is a worldwide cause of morbidity and mortality. Pentraxin 3 (PTX3) is a humoral component of the innate immune system which has been studied as a marker of inflammatory, infections or cardiovascular pathologies. To investigate the association between serum levels of PTX3 and the hospital mortality of patients with severe TBI. METHODS: The independent association between serum PTX3 levels after severe TBI (Glasgow Coma Scale, GCS ≤ 8) and hospital mortality was analyzed in a prospective study of 83 consecutive patients by a multiple logistic regression analysis. The leukocyte count in the same sample was analyzed as another marker of inflammatory response. RESULTS: The mean age of patients was 35 years and 85% were male. Serum PTX3 levels were determined 18.0 (SD ± 17.0) h after TBI. Patients who died showed a mean serum PTX3 level of 9.95 µg/ml (SD ± 6.42) in comparison to 5.46 µg/ml (SD ± 4.87) of the survivor group (P = 0.007). Elevated serum PTX3 levels remain significantly associated with mortality (P = 0.04) in the subset of patients with isolated TBI (n = 34). There were no differences in the leukocytes count measured in the same blood sample used for PTX3 determination in survivors and non-survivors (P = 0.56). The final multiple logistic regression model including age, pupillary examination, GCS, associated trauma, and PTX3 levels shows that serum levels of PTX3 which were higher than 10 µg/ml were independently associated with the patients mortality (adjusted OR 3.06, CI 95% 1.03-9.15, P = 0.04). CONCLUSIONS: Serum PTX3 levels after severe TBI are independently associated with higher hospital mortality and may be a useful marker of TBI and its prognosis.
Assuntos
Biomarcadores/sangue , Lesões Encefálicas/diagnóstico , Lesões Encefálicas/mortalidade , Proteína C-Reativa/metabolismo , Mortalidade Hospitalar , Componente Amiloide P Sérico/metabolismo , Adolescente , Adulto , Lesões Encefálicas/imunologia , Feminino , Escala de Coma de Glasgow , Humanos , Contagem de Leucócitos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto JovemRESUMO
It has been reported that upwards of 50% of patients who survive an initial brain traumatic insult subsequently die due to infection and multiple organ failure. A paralysis of cell-mediated immunity following trauma, partially induced by anti-inflammatory cytokine release, appears to be responsible for the increased susceptibility to infections. We determined the plasma levels of the anti-inflammatory cytokine IL-10 and the pro-inflammatory TNF-alpha in 15 patients admitted with severe traumatic brain injury (TBI). None of the patients had received glucocorticoid or catecholamine treatment. Thirteen volunteers served as controls. At study entry the IL-10 plasma levels were significantly higher than in controls: 41.8 (17.3-265.4) pg/mL vs. 2.2 (1.4-2.7) pg/mL, p < 0.001 (Mann-Whitney test). There was no difference between the first (at study entry) and second sample (4 hours later) (Wilcoxon test). TNF-alpha plasma levels were similar in patients and controls at study entry and 4 hours later. We conclude that severe TBI patients present an early response, with a significant increase of IL-10 plasma levels. These results could partially explain the immunodepression following TBI.