Memory deficit associated with increased brain proinflammatory cytokine levels and neurodegeneration in acute ischemic stroke / Déficit de memória associado ao aumento dos níveis cerebrais de citocinas pró-inflamatórias e neurodegeneração na isquemia cerebral aguda

The present study aimed to investigate behavioral changes and neuroinflammatory process following left unilateral common carotid artery occlusion (UCCAO), a model of cerebral ischemia. Post-ischemic behavioral changes following 15 min UCCAO were recorded 24 hours after reperfusion. The novel object recognition task was used to assess learning and memory. After behavioral test, brains from sham and ischemic mice were removed and processed to evaluate central nervous system pathology by TTC and H&E techniques as well as inflammatory mediators by ELISA. UCCAO promoted long-term memory impairment after reperfusion. Infarct areas were observed in the cerebrum by TTC stain. Moreover, the histopathological analysis revealed cerebral necrotic cavities surrounded by ischemic neurons and hippocampal neurodegeneration. In parallel with memory dysfunction, brain levels of TNF-a, IL-1b and CXCL1 were increased post ischemia compared with sham-operated group. These findings suggest an involvement of central nervous system inflammatory mediators and brain damage in cognitive impairment following unilateral acute ischemia.

O presente estudo teve como objetivo investigar alterações comportamentais e processos inflamatórios na isquemia cerebral induzida pela oclusão unilateral da carótida comum esquerda (UCCAO) em camundongos. As alterações comportamentais foram avaliadas após 15 minutos de isquemia e 24 horas de reperfusão. O teste de reconhecimento de objetos foi utilizado para avaliação da memória e do aprendizado. Em seguida, os animais foram mortos e os encéfalos foram coletados e processados para avaliação das alterações patológicas pelas técnicas de TTC e H&E, assim como da dosagem de mediadores inflamatórios por ELISA. A UCCAO promoveu alterações de memória após a reperfusão. Foram visualizadas áreas de infarto cerebral pela coloração de TTC e cavidades necróticas circundadas por neurônios isquêmicos no cérebro e neurodegeneração hipocampal. A UCCAO causou aumento dos níveis encefálicos de TNF-a, IL-1b e CXCL1. Estes achados demonstraram o envolvimento dos mediadores inflamatórios no sistema nervoso central e da neurodegeneração no déficit cognitivo após isquemia cerebral aguda.

Relationship between cardiovascular risk factors and the echogenicity and pattern of the carotid intima-media complex in men / Relação entre os fatores de risco cardiovascular e a ecogenicidade e o padrão do complexo íntima-média carotídeo em homens

CONTEXT AND OBJECTIVE: The thickness of the carotid intima-media complex (C-IMC) is considered to be a marker of early atherosclerosis, but visual and echogenic changes to the C-IMC can also be noted. The objective here was to evaluate the relationship between cardiovascular risk factors and the echogenicity of the C-IMC and identify those most associated with an "abnormal" C-IMC. DESIGN AND SETTING: Cross-sectional study in the ultrasound sector of the Department of Diagnostic Imaging, Universidade Federal de São Paulo. METHODS: Eighty men were evaluated. Measurements of arterial blood pressure, waist circumference (WC), lipid profile, fasting glucose, uric acid and high-sensitivity C-reactive protein were obtained. The thickness of the C-IMC was measured by means of B-mode ultrasound, and the intima-media gray-scale mean (IM-GSM) and standard deviation (IM-SD) were calculated. RESULTS: The following were discriminating variables: fasting glucose (r2 = 0.036; P = 0.013), uric acid (r2 = 0.08; P = 0.03), IM-SD (r2 = 0.43; P < 0.001), IM-GSM (r2 = 0.35; P < 0.001) and thickness of the C-IMC (r2 = 0.29; P < 0.001). IM-GSM showed significant correlations with WC (r = -0.22; P = 0.005), fasting glucose (r = -0.24; P = 0.002) and high-density lipoprotein cholesterol (HDL-C) (r = 0.27; P = 0.0007). CONCLUSION: IM-GSM showed correlations with WC, fasting glucose and HDL-C. However, uric acid and IM-SD presented the greatest discriminating impact. These results suggest that visual changes in C-IMC may help identify patients with potential cardiovascular risk, independently of the thickness of the C-IMC. .

CONTEXTO E OBJETIVO: A espessura do complexo íntima-média carotídeo (CIM-C) é considerada um marcador da aterosclerose precoce, mas alterações visuais e da ecogenicidade do CIM-C também podem ser observadas. O objetivo foi avaliar a relação entre os fatores de risco cardiovascular e a ecogenicidade do CIM-C e identificar aqueles mais relacionados com o CIM-C "alterado". TIPO DE ESTUDO E LOCAL: Estudo transversal no setor de ultrassonografia do Departamento de Diagnóstico por Imagem, Universidade Federal de São Paulo. MÉTODOS: Oitenta homens foram avaliados. Aferição da pressão arterial, medida da circunferência abdominal (CA), perfil lipídico, glicemia de jejum (GLI), ácido úrico (AU) e proteína C-reativa de alta sensibilidade foram obtidos. A espessura do CIM-C foi medida por ultrassom modo B e a média da escala de cinza (GSM) e do desvio padrão do CIM (DPIM) foram calculados. RESULTADOS: As variáveis discriminantes foram GLI (r2 = 0,036; P = 0,013), AU (r2 = 0,08; P = 0,03), DPIM (r2 = 0,43; P < 0,001), GSM (r2 = 0,35; P < 0,001) e espessura do CIM-C (r2 = 0.29; P < 0,001). Houve correlação significativa entre GSM e CA (r = -0,22; P = 0,005), GLI (r = -0,24; P = 0,002) e lipoproteína de alta densidade do colesterol (HDL-C) (r = 0,27; P = 0,0007). CONCLUSÃO: A GSM teve correlação com CA, GLI, HDL-C. Entretanto, AU e DPIM apresentaram maior impacto discriminante, sugerindo que alterações visuais do CIM-C, independentemente da espessura, podem auxiliar na identificação de pacientes com potencial risco cardiovascular. .

Learning and survival memory undergoing a permanent bilateral carotid ligation in rats

PURPOSE: To evaluate the effect of cerebral hypoxia-ischemia on memory and learning survival of rats submitted to permanent bilateral carotid ligation (PBCL). METHODS: Twenty-four survivors of PBCL were evaluated after 30 days with regard to memory and learning using a water survival maze. Twenty-three healthy rats were used as control group. The results were expressed by their means and standard error of the mean (SEM). p<0.05 was used for rejecting the null hypothesis. The study was approved by the Ethics Committee for animal investigation. RESULTS: The mortality rate for the surgery was 44.4%. The latency time to find the survival platform was higher in rats that underwent PBCL (Normal: 10.24 ± 1.85s - Study: 25.30 ± 4.69s - Mann - Whitney p=0.0388). Additionally, the type of swimming and the spatial stability of the studied rats on the survival platform were compromised in these animals. CONCLUSION: The permanent bilateral carotid ligation induces change in the learning and survival memory.

Análise estrutural e funcional carotídea em familiares de pacientes com diabete melito tipo 2 / Carotid artery structural and functional evaluation in relatives of type 2 diabetic patients / Estudio estructural y funcional carotídeo en familiares de pacientes con diabetes mellitus tipo 2

FUNDAMENTO: O diabete melito tipo 2 (DM2) é a principal causa de morbidade e mortalidade nos países ocidentais, principalmente de origem cardiovascular. Com base na história familiar de diabete, mesmo em indivíduos não-diabéticos, como aumento de risco de doença cardíaca coronariana, faz-se necessária a utilização de reconhecidos marcadores substitutos de aterosclerose precoce, como as medidas ecográficas carotídeas. OBJETIVO:Comparar tanto características estruturais (espessura médio-intimal - EMI) quanto funcionais (medidas de distensibilidade) de artérias carotídeas dos indivíduos com história familiar (HF+) e dos não-parentes de portadores de DM2 (HF-), todos sem fatores de risco cardiovasculares reconhecidos. MÉTODOS:Trinta e dois indivíduos (19 HF+ e 13 HF-), com idade entre 21 e 47 anos, de ambos os sexos, foram submetidos a estudo ultra-sonográfico de alta resolução das carótidas (comuns e internas) bilateralmente. Os grupos apresentavam comparação (p > 0,05) no que tangia a idade, índice de massa corporal (IMC), pressão arterial, glicose e insulina de jejum, leptina e proteína C reativa (PCR). RESULTADOS:A espessura médio-intimal das artérias carótidas comuns esquerdas (ACCE) foi estatisticamente mais elevada (p = 0,029) nos HF+ (0,568 ± 0,107 mm) que nos HF- (0,477± 0,116 mm). A análise de regressão múltipla identificou como prognosticadores independentes da EMI de ACCE a idade, o IMC acima da normalidade, a PCR e o LDL-colesterol. CONCLUSÃO:Indivíduos com história familiar de DM2, mesmo sem desordens metabólicas laboratoriais detectadas, apresentaram maior espessamento médio-intimal em território carotídeo comum esquerdo que aqueles sem tal parentesco, no entanto não houve alteração funcional do vaso.

In Western countries type 2 diabetes mellitus (DM2) is the leading cause of morbidity and mortality, particularly from cardiovascular causes. Since a family history of diabetes, even in non-diabetic subjects, is regarded as an increased risk of coronary heart disease, the use of approved surrogate markers of early atherosclerosis, specially of ultrasonic measurements of the carotid arteries, is of vital importance. OBJECTIVE: To analyze the structural properties (intima-media thickness) and functional properties (distensibility measurement) of the carotid arteries in subjects with (FH+) a family history of type 2 diabetes, in comparison to subjects without (FH-) a family history of type 2 diabetes, both groups with no known cardiovascular risk factors. METHODS: 32 individuals (male and female, age range, 21-47 years; 19 FH+, 13 FH-) had their right and left common and internal carotid arteries measured, using high-resolution B-mode ultrasonography. Both groups had similar (p>0.05) age, BMI, blood pressure, and fasting blood glucose and insulin, leptin, and C-reactive protein (CRP) levels. RESULTS: The intima-media thickness (IMT) of the left common carotid artery (LCCA) in the FH+ group (0.568±0.107mm) was statistically greater (p=0.029) than in the FH- group (0.477±0.116mm). Multiple regression analysis identified age, overweight and obesity (determined by BMI), CRP, and LDL-cholesterol levels as independent predictors of the IMT in the LCCA. CONCLUSION: FH+ individuals with no metabolic disorders presented greater IMT of the left common carotid artery (structural alteration) than FH- individuals, but normal vessel function.

FUNDAMENTO: La diabetes mellitus tipo 2 (DM2) es la principal causa de morbilidad y mortalidad en los países occidentales, principalmente de origen cardiovascular. Con base en la historia familiar de diabetes - aun en individuos no diabéticos -, ante el aumento de riesgo de enfermedad cardiaca coronaria, se hace necesaria la utilización de reconocidos marcadores sustitutos de aterosclerosis precoz, como las mediciones por ecografía carotídea. OBJETIVO: Comparar tanto características estructurales (espesor íntima-medio - EIM) como funcionales (medidas de distensibilidad) de arterias carotídeas de los individuos con historia familiar (HF+) y de los no parientes de portadores de DM2 (HF-), todos sin factores de riesgo cardiovasculares reconocidos. MÉTODOS: Un total de 32 individuos (19 HF+ y 13 HF-), con edad entre 21 y 47 años, de ambos sexos, fueron sometidos a estudio ultrasonográfico de alta resolución de las carótidas (comunes e internas) bilateralmente. Los grupos presentaban comparación (P > 0,05) de edad, índice de masa corporal (IMC), presión arterial, glucosa y insulina de ayuno, leptina y proteína C reactiva (PCR). RESULTADOS: El espesor íntima-medio de las arterias carótidas comunes izquierdas (ACCI) se mostró estadísticamente más elevado (P = 0,029) en los HF+ (0,568 ± 0,107 mm) que en los HF- (0,477± 0,116 mm). El análisis de regresión múltiple identificó como pronosticadores independientes de la EIM de ACCI la edad, el IMC superior al normal, la PCR y el LDL-colesterol. CONCLUSIÓN: Individuos con historia familiar de DM2, aun sin desórdenes metabólicas laboratoriales detectadas, presentaron mayor espesor íntima-medio en territorio carotídeo común izquierdo que pacientes sin tal parentesco. Sin embargo, no hubo alteración funcional de la arteria.

Prevalence of peripheral arterial disease by ankle-brachial index and its correlation with carotid intimal thickness and coronary risk factors in Nepalese population over the age of forty years.

OBJECTIVES: Noninvasive measures of subclinical atherosclerosis such as the ankle brachial index (ABI) and common carotid artery intima-media thickness (CCA IMT) could improve risk prediction and provide more focused primary prevention strategies. This report describes the prevalence of subclinical atherosclerotic vascular disease in a Nepalese population over the age of forty years as measured by ABI and CCA IMT and their association with established cardiovascular risk factors. MATERIALS AND METHODS: Ultrasonic evaluation of ABI and CCA IMT was done in 195 individuals of age 40 years and above who had presented to an outpatient department. Patients with established diagnosis of coronary artery disease or symptomatic for peripheral arterial disease were excluded from the study. RESULTS: The prevalence of atherosclerotic disease as measured by ABI was 18.5% and there was a statistically significant correlation between ABI and CCA IMT and other established cardiovascular risk factors such as smoking, diabetes mellitus and hypertension. CONCLUSIONS: We recommend that ABI as measured by sphygmomanometer be incorporated into routine cardiovascular screening and when found to be abnormal further confirmed by Doppler assessment of ABI and CCA IMT as surrogate markers of atherosclerotic vascular disease.