D-Lactate and intestinal fatty acid-binding protein are elevated in serum in patients with acute ischemic stroke.

Experimental studies suggest that the intestinal barrier is affected in ischemic stroke. D-Lactate and intestinal fatty acid-binding protein (IFABP) are markers of intestinal mucosa integrity and barrier function. Our purpose was to evaluate the serum concentrations of these markers in patients with acute ischemic stroke (AIS). We included patients with AIS and used healthy subjects as controls. Clinical, demographic and outcome measures were recorded. Blood was drawn within 24 h of symptom onset. Serum concentrations of D-Lactate and IFABP were determined using commercially available colorimetric and ELISA kits, respectively. We included a total of 61 patients (median age of 64 years). The majority of patients were male (57.4%). The most common cause of stroke was atherosclerosis (34.4%), followed by small-vessel disease and cardioembolic (32.7% each). Mean admission NIHSS score was 8. Median IFABP and D-Lactate concentrations were significantly higher in patients than in controls. Concentrations were not associated with stroke severity or 3-month outcome. Patients with large-artery atherosclerosis and cardioembolic etiology had higher D-Lactate values than patients with small-vessel disease. D-Lactate and IFABP were significantly elevated in patients with AIS. This suggests that there is disruption of the intestinal barrier in patients with AIS.

Inversão total do fluxo em artéria carótida interna direita em paciente com estenose grave do tronco braquiocefálico / Total reversal of internal carotid blood flow in a patient with severe stenosis of the brachiocephalic trunk

RESUMO As estenoses graves e oclusões do tronco braquiocefálico (artéria inominada) são raras, e apresentam uma grande variedade de manifestações clínicas, com alterações relacionadas a isquemia cerebral hemisférica, vertebrobasilar e de membro superior direito. A causa mais comum é a aterosclerose. A ultrassonografia vascular com Doppler pode revelar inversão de fluxo na artéria vertebral direita, hipofluxo na subclávia, e vários tipos de alterações no fluxo da carótida direita, incluindo hipofluxo, inversão parcial do fluxo durante o ciclo cardíaco, e até mesmo inversão completa do fluxo na carótida interna, achado este bastante raro. Os autores descrevem o caso de paciente do sexo feminino, tabagista, com estenose grave do tronco braquiocefálico e crises de lipotimia. Além do roubo de artéria subclávia e do fluxo parcialmente invertido na carótida comum direita, a paciente apresentava exuberante fluxo invertido na carótida interna durante todo o ciclo cardíaco, achado este não encontrado na literatura em tamanha magnitude.

ABSTRACT Occlusions and severe stenoses of the innominate artery (brachiocephalic trunk) are rare and present with a wide variety of clinical manifestations, with hemispheric, vertebrobasilar and right upper limb ischemic symptoms. The most common cause is atherosclerosis. Duplex scanning may show right vertebral artery flow reversal, diminished subclavian flow, and several patterns of right carotid flow disturbance, including slow flow, partial flow reversal during the cardiac cycle and even complete reversal of flow in the internal carotid artery, which is a very uncommon finding. Herein, the authors describe the case of a female patient who was a heavy smoker, had severe stenosis of the brachiocephalic trunk, and had episodes of collapse. Besides the subclavian steal and partial flow reversal in the common carotid artery, duplex scanning also showed high-velocity reversed flow in the internal carotid artery during the entire cardiac cycle, a finding that is not reported in the literature at this magnitude.

Analysis of Caspase-9 protein and microRNAs miR-21, miR-126 and miR-155 related to the apoptosis mechanism in the cerebellum of rats submitted to focal cerebral ischemia associated with an alcoholism model.

OBJECTIVE: This study aimed to analyze the cerebellum of rats submitted to an experimental focal cerebral ischemia, by middle cerebral artery occlusion for 90 minutes, followed by reperfusion for 48 hours, associated with an alcoholism model. METHODS: Fifty adult Wistar rats were used, subdivided into five experimental groups: control group (C): animals submitted to anesthesia only; sham group (S): animals submitted to complete simulation of the surgical procedure; ischemic group (I): animals submitted to focal cerebral ischemia for 90 minutes followed by reperfusion for 48 hours; alcoholic group (A): animals that received daily absolute ethanol diluted 20% in water for four weeks; and, ischemic and alcoholic group (I + A): animals receiving the same treatment as group A and, after four weeks, submitted to focal cerebral ischemia for 90 minutes, followed by reperfusion for 48 hours. The cerebellum samples were collected and immunohistochemical analysis of Caspase-9 protein and serum analysis by RT-PCR of microRNAs miR-21, miR-126 and miR155 were performed. RESULTS: The expression of Caspase-9 was higher in groups I, A and I + A. In the microRNAs analyses, miR-126 was higher in groups A and I + A, miR-155 was higher in groups I and I + A. CONCLUSIONS: We conclude that apoptosis occurs in the cerebellar cortex, even if it is distant from the ischemic focus, and that microRNAs 126 and 155 show a correlation with cellular apoptosis in ischemic rats and those submitted to the chronic alcohol model.

Hypothermia treatment ameliorated cyclin-dependent kinase 5-mediated inflammation in ischemic stroke and improved outcomes in ischemic stroke patients.

OBJECTIVES: The inflammatory response is a key mechanism of neuronal damage and loss during acute ischemic stroke. Hypothermia has shown promise as a treatment for ischemic stroke. In this study, we investigated the molecular signaling pathways in ischemic stroke after hypothermia treatment. METHODS: Cyclin-dependent kinase 5 (CDK5) was overexpressed or silenced in cultured cells. Nuclear transcription factor-κB (NF-κB) activity was assessed by measurement of the luciferase reporter gene. An ischemic stroke model was established in Sprague-Dawley (SD) rats using the suture-occluded method. Animals were assigned to three groups: sham operation control, ischemic stroke, and ischemic stroke + hypothermia treatment groups. Interleukin 1ß (IL-1ß) levels in the culture supernatant and blood samples were assessed by ELISA. Protein expression was measured by Western blotting. RESULTS: In HEK293 cells and primary cortical neuronal cultures exposed to hypothermia, CDK5 overexpression was associated with increased IL-1ß, caspase 1, and NF-κB levels. In both a murine model of stroke and in patients, increased IL-1ß levels were observed after stroke, and hypothermia treatment was associated with lower IL-1ß levels. Furthermore, hypothermia-treated patients showed significant improvement in neurophysiological functional outcome. CONCLUSIONS: Overall, hypothermia offers clinical benefit, most likely through its effects on the inflammatory response.

Analysis of Caspase-9 protein and microRNAs miR-21, miR-126 and miR-155 related to the apoptosis mechanism in the cerebellum of rats submitted to focal cerebral ischemia associated with an alcoholism model / Análise da proteína Caspase-9 e dos microRNAs miR-21, miR-126 e miR-155 relacionados ao mecanismo de apoptose no cerebelo de ratos submetidos à isquemia cerebral focal associada ao modelo de alcoolismo

ABSTRACT This study aimed to analyze the cerebellum of rats submitted to an experimental focal cerebral ischemia, by middle cerebral artery occlusion for 90 minutes, followed by reperfusion for 48 hours, associated with an alcoholism model. Methods Fifty adult Wistar rats were used, subdivided into five experimental groups: control group (C): animals submitted to anesthesia only; sham group (S): animals submitted to complete simulation of the surgical procedure; ischemic group (I): animals submitted to focal cerebral ischemia for 90 minutes followed by reperfusion for 48 hours; alcoholic group (A): animals that received daily absolute ethanol diluted 20% in water for four weeks; and, ischemic and alcoholic group (I + A): animals receiving the same treatment as group A and, after four weeks, submitted to focal cerebral ischemia for 90 minutes, followed by reperfusion for 48 hours. The cerebellum samples were collected and immunohistochemical analysis of Caspase-9 protein and serum analysis by RT-PCR of microRNAs miR-21, miR-126 and miR155 were performed. Results The expression of Caspase-9 was higher in groups I, A and I + A. In the microRNAs analyses, miR-126 was higher in groups A and I + A, miR-155 was higher in groups I and I + A. Conclusions We conclude that apoptosis occurs in the cerebellar cortex, even if it is distant from the ischemic focus, and that microRNAs 126 and 155 show a correlation with cellular apoptosis in ischemic rats and those submitted to the chronic alcohol model.

RESUMO O objetivo deste estudo foi analisar o cerebelo de ratos submetidos à isquemia cerebral focal experimental, por oclusão da artéria cerebral média por 90 minutos, seguida de reperfusão por 48 horas, associada a um modelo de alcoolismo. Métodos Foram utilizados 50 ratos Wistar adultos, subdivididos em cinco grupos experimentais: grupo controle (C): animais submetidos apenas à anestesia; grupo sham (S): animais submetidos à simulação completa do procedimento cirúrgico; grupo isquêmico (I): animais submetidos à isquemia cerebral focal por 90 minutos, seguidos de reperfusão por 48 horas; grupo alcoólico (A): animais que receberam etanol absoluto diário diluído em 20% em água por quatro semanas; e grupo isquêmico e alcoólico (I + A): animais que recebem o mesmo tratamento do grupo A e, após quatro semanas, submetidos à isquemia cerebral focal por 90 minutos, seguidos de reperfusão por 48 horas. As amostras de cerebelo foram coletadas e a análise imuno-histoquímica da proteína Caspase-9 e a análise sérica por RT-PCR dos microRNAs miR-21, miR-126 e miR155 foram realizadas. Resultados A expressão de Caspase-9 foi maior nos grupos I, A e I + A. Nas análises de microRNAs, o miR-126 foi maior nos grupos A e I + A, o miR-155 foi maior nos grupos I e I + A. Conclusões Concluímos que a apoptose ocorre no córtex cerebelar, mesmo distante do foco isquêmico, e que os microRNAs 126 e 155 mostram uma correlação com a apoptose celular em ratos isquêmicos e submetidos ao modelo crônico de álcool.

Lipid transfer to high-density lipoproteins in coronary artery disease patients with and without previous cerebrovascular ischemic events.

BACKGROUND: Patients with coronary artery disease (CAD) and previous ischemic cerebrovascular events (ICVE, ischemic stroke, or transitory ischemic attack) constitute a high-risk subgroup for cardiovascular outcomes. High-density lipoprotein cholesterol (HDL-C) levels are correlated with cardiovascular events. Lipid transfer to HDL affects structure size and HDL subclass profile. Impairment of this transfer could influence ischemic risk seen in patients with CAD + ICVE. The objective was to evaluate the HDL ability to receive the lipids in patients with CAD with or without ICVE. METHODS: Patients with CAD + ICVE (n = 60) and patients with CAD only (n = 60) were matched by age, sex, acute coronary syndromes (ACS) event type, and time elapsed between the ACS event and inclusion in the study. Lipid transfer to HDL was evaluated by incubating donor lipid nanoparticles labeled with radioactive unesterified cholesterol (UC) and esterified cholesterol (EC), phospholipid (PL), and triglyceride (TG) with whole plasma. After the chemical precipitation of non-HDL fractions and nanoparticles, the supernatant was counted for HDL radioactivity. RESULTS: CAD + ICVE group presented with impaired lipid transfer to HDL for PL (CAD + ICVE: 21.14 ± 2.7% vs CAD: 21.67 ± 3.1%, P = .03), TG (CAD + ICVE: 4.88 ± 0.97% vs CAD: 5.63 ± 0.92%, P = .002), and UC (CAD + ICVE: 5.55 ± 1.19% vs CAD: 6.16 ± 1.14%, P = .009). Lipid transfer to HDL was similar in both groups for EC. Adjusted models showed similar results. CONCLUSION: Patients with CAD and ICVE have reduced lipid transfer to HDL compared to those with CAD only. Dysfunctional HDL may account for the higher incidence of ischemic outcomes observed in this population.

Immune-inflammatory, oxidative stress and biochemical biomarkers predict short-term acute ischemic stroke death.

The aim of the study was to define new immune-inflammatory, oxidative stress and biochemical biomarkers, which predict mortality within a period of 3 months after acute ischemic stroke (AIS). We recruited 176 healthy volunteers and 145 AIS patients, categorized as AIS survivors and non-survivors, and measured interleukin (IL)-6, high sensitivity C-reactive protein (hsCRP), ferritin, iron, total serum protein (TSP), erythrocyte sedimentation rate (ESR), white blood cells (WBC), 25 hydroxyvitamin D [25(OH)D], lipid hydroperoxides (CL-LOOH), insulin, glucose and high-density lipoprotein (HDL)-cholesterol. In patients, these biomarkers were measured within 24 h after AIS onset. We also computed two composite scores reflecting inflammatory indices, namely INFLAM index1 (sum of z scores of hsCRP+IL-6 + ferritin+ESR + WBC) and INFLAM index2 (z INFLAM index1 - z 25(OH)D - z iron + z TSP). Three months after AIS, non-survivors (n = 54) showed higher baseline levels of IL-6, hsCRP, ferritin and glucose and lower levels of HDL-cholesterol and 25(OH)D than survivors (n = 91). Non-survivors showed higher baseline ESR and lowered TSP than controls, while survivors occupied an intermediate position. Death after AIS was best predicted by increased IL-6, glucose, ferritin and CL-LOOH and lowered 25(OH)D levels. The area under the receiver operating curves computed on the INFLAM index1 and 2 scores were 0.851 and 0.870, respectively. In conclusion, activation of peripheral immune-inflammatory, oxidative and biochemical pathways is critically associated with mortality after AIS. Our results may contribute to identify new biomarker sets, which may predict post-stroke death, as well as suggest that IL-6 trans-signaling coupled with redox imbalances may be possible new targets in the prevention of short-term outcome AIS death.

Amino Acid Biosignature in Plasma among Ischemic Stroke Subtypes.

Ischemic stroke is a neurovascular disorder caused by reduced or blockage of blood flow to the brain, which may permanently affect motor and cognitive abilities. The diagnostic of stroke is performed using imaging technologies, clinical evaluation, and neuropsychological protocols, but no blood test is available yet. In this work, we analyzed amino acid concentrations in blood plasma from poststroke patients in order to identify differences that could characterize the stroke etiology. Plasma concentrations of sixteen amino acids from patients with chronic ischemic stroke (n = 73) and the control group (n = 16) were determined using gas chromatography coupled to mass spectrometry (GC-MS). The concentration data was processed by Partial Least Squares-Discriminant Analysis (PLS-DA) to classify patients with stroke and control. The amino acid analysis generated a first model able to discriminate ischemic stroke patients from control group. Proline was the most important amino acid for classification of the stroke samples in PLS-DA, followed by lysine, phenylalanine, leucine, and glycine, and while higher levels of methionine and alanine were mostly related to the control samples. The second model was able to discriminate the stroke subtypes like atherothrombotic etiology from cardioembolic and lacunar etiologies, with lysine, leucine, and cysteine plasmatic concentrations being the most important metabolites. Our results suggest an amino acid biosignature for patients with chronic stroke in plasma samples, which can be helpful in diagnosis, prognosis, and therapeutics of these patients.

Hypothermia treatment ameliorated cyclin-dependent kinase 5-mediated inflammation in ischemic stroke and improved outcomes in ischemic stroke patients

OBJECTIVES: The inflammatory response is a key mechanism of neuronal damage and loss during acute ischemic stroke. Hypothermia has shown promise as a treatment for ischemic stroke. In this study, we investigated the molecular signaling pathways in ischemic stroke after hypothermia treatment. METHODS: Cyclin-dependent kinase 5 (CDK5) was overexpressed or silenced in cultured cells. Nuclear transcription factor-κB (NF-κB) activity was assessed by measurement of the luciferase reporter gene. An ischemic stroke model was established in Sprague-Dawley (SD) rats using the suture-occluded method. Animals were assigned to three groups: sham operation control, ischemic stroke, and ischemic stroke + hypothermia treatment groups. Interleukin 1β (IL-1β) levels in the culture supernatant and blood samples were assessed by ELISA. Protein expression was measured by Western blotting. RESULTS: In HEK293 cells and primary cortical neuronal cultures exposed to hypothermia, CDK5 overexpression was associated with increased IL-1β, caspase 1, and NF-κB levels. In both a murine model of stroke and in patients, increased IL-1β levels were observed after stroke, and hypothermia treatment was associated with lower IL-1β levels. Furthermore, hypothermia-treated patients showed significant improvement in neurophysiological functional outcome. CONCLUSIONS: Overall, hypothermia offers clinical benefit, most likely through its effects on the inflammatory response.

Mecobalamin and early functional outcomes of ischemic stroke patients with H-type hypertension.

OBJECTIVE: To analyze the effect of mecobalamin on the early-functional outcomes of patients with ischemic stroke and H-type hypertension. METHODS: From October of 2014 to October of 2016, 224 cases of ischemic stroke and H-type hypertension were selected. The patients were randomly divided into treatment control groups, with 112 patients in each group. The control group was treated with the conventional therapy. The observation group was treated with 500 µg of mecobalamin three times a day in addition to the conventional therapy. We compared serum homocysteine (Hcy), hs-CRP levels, carotid plaques, and NIHSS scores between the two groups on the 2nd day and at 4 weeks, 8 weeks, 3 months, and 6 months. RESULTS: After 4 weeks, 8 weeks, 3 months and 6 months, the difference of serum Hcy level between the two groups was statistically significant (t = 4.049, 3.896, 6.052, 6.159, respectively. All P <0.05). After the treatment, at 4 weeks, 8 weeks, 3 months and 6 months, the levels of hs-CRP in the treatment group were significantly lower than those in the control group (t = 37.249, 28.376, 26.454, 20.522, respectively. All P <0.01). After 3 months and 6 months, the carotid artery plaques were significantly reduced in the treatment group compared to those in the control group (t = 2.309 and 2.434. All P <0.05). After 3 months and 6 months, the NIHSS score was significantly higher in the treatment group compared to those in the control group (t = 2.455 and 2.193. All P <0.05). CONCLUSION: Mecobalamin can reduce the level of plasma homocysteine, then lead to reductions of levels of plasma inflammatory factors and volume of carotid artery plaques, resulting in more significant functional recovery.

Mecobalamin and early functional outcomes of ischemic stroke patients with H-type hypertension

SUMMARY OBJECTIVE To analyze the effect of mecobalamin on the early-functional outcomes of patients with ischemic stroke and H-type hypertension. METHODS From October of 2014 to October of 2016, 224 cases of ischemic stroke and H-type hypertension were selected. The patients were randomly divided into treatment control groups, with 112 patients in each group. The control group was treated with the conventional therapy. The observation group was treated with 500 µg of mecobalamin three times a day in addition to the conventional therapy. We compared serum homocysteine (Hcy), hs-CRP levels, carotid plaques, and NIHSS scores between the two groups on the 2nd day and at 4 weeks, 8 weeks, 3 months, and 6 months. RESULTS After 4 weeks, 8 weeks, 3 months and 6 months, the difference of serum Hcy level between the two groups was statistically significant (t = 4.049, 3.896, 6.052, 6.159, respectively. All P <0.05). After the treatment, at 4 weeks, 8 weeks, 3 months and 6 months, the levels of hs-CRP in the treatment group were significantly lower than those in the control group (t = 37.249, 28.376, 26.454, 20.522, respectively. All P <0.01). After 3 months and 6 months, the carotid artery plaques were significantly reduced in the treatment group compared to those in the control group (t = 2.309 and 2.434. All P <0.05). After 3 months and 6 months, the NIHSS score was significantly higher in the treatment group compared to those in the control group (t = 2.455 and 2.193. All P <0.05). CONCLUSION Mecobalamin can reduce the level of plasma homocysteine, then lead to reductions of levels of plasma inflammatory factors and volume of carotid artery plaques, resulting in more significant functional recovery.

RESUMO OBJETIVO Analisar o efeito de mecobalamin sobre os primeiros resultados funcionais de pacientes com AVC isquêmico e hipertensão H-type. MÉTODOS De outubro de 2014 a outubro de 2016, 224 casos de AVC isquêmico e hipertensão H-type foram selecionadas. Os pacientes foram divididos aleatoriamente em grupo de tratamento e grupo controle, com 112 doentes em cada grupo. O grupo controle foi tratado com a terapia de rotina. O grupo de observação foi tratado com 500 µg de mecobalamin três vezes por dia, além da rotina de tratamento. No segundo dia, 4 semanas, 8 semanas, 3 meses e 6 meses, comparamos níveis séricos da homocisteína (Hcy) e de hs-CRP, placas da carótida e pontuações NIHSS entre os dois grupos. RESULTADOS Após 4 semanas, 8 semanas, 3 meses e 6 meses, a diferença dos níveis séricos de Hcy entre os dois grupos foi estatisticamente significativa (t= 4,049, 3,896, 6,052, 6,159, respectivamente. Todos os P<0,05). Após o tratamento de 4 semanas, 8 semanas, 3 meses e 6 meses, os níveis de hs-CRP no grupo de tratamento foram significativamente inferiores aos do grupo controle (t=37,249, 28,376, 26,454, 20,522, respectivamente. Todos os P<0,01). Depois de 3 meses e 6 meses, as placas da artéria carótida foram significativamente reduzidas no tratamento, em comparação com os do grupo controle (t=2,309 e 2,434. Todos os P<0,05). Depois de 3 meses e 6 meses, as pontuações NIHSS foram significativamente mais elevadas no tratamento em comparação com as do grupo controle (t=2,455 e 2,193. Todos os P<0,05). CONCLUSÃO Mecobalamin pode reduzir o nível de homocisteína plasmática, o que conduz à redução dos níveis de plasma inflamatórios e do volume das placas na artéria carótida, resultando em maior recuperação funcional.

The Methylenetetrahydrofolate Reductase C677T (rs1801133) and Apolipoprotein A5-1131T>C (rs662799) Polymorphisms, and Anemia Are Independent Risk Factors for Ischemic Stroke.

BACKGROUND: Although there is adequate knowledge as to the role of traditional cardiovascular risk factors on stroke incidence, knowledge of other risk factors, particularly genetic ones, is still incomplete. METHODS: To assess the participation of some polymorphisms, along with other modifiable risk factors, a case-control study was conducted. A total of 253 cases were identified in the emergency room of a general regional hospital, with a clinical trait of stroke confirmed by a skull computerized axial tomography scan. In the surgery ward, 253 controls were identified, gender and age (±5 years) matched. Biochemical parameters were measured, and 4 polymorphisms were genotyped by polymerase chain reaction, rs1801133 (methylenetetrahydrofolate reductase [MTHFR]), rs1498373 (dimethylarginine dimethylaminohydrolase type 1 [DDAH1]), rs662799 (apolipoprotein A5 [APOA5]), and rs1799983 (endothelial nitric oxide). Odds ratios were estimated to assess the strength of association, with 95% confidence intervals, both in a matched case-control analysis and in a conditional regression analysis. RESULTS: Cases had higher mean blood pressure and triglycerides and lower hemoglobin levels. Heterozygous and homozygous subjects to the rs1801133 variant of the MTHFR gene had a 3-fold higher risk of stroke. In the dominant model, those with the polymorphism rs662799 of the promoter region for APOA5 had twice the risk of stroke. Anemia increased the risk of stroke 4-fold. CONCLUSIONS: Polymorphisms of the genes MTHFR (rs1801133) and APOA5 (rs662799), as well as anemia, are independent risk factors for stroke in Mexicans, together with traditional cardiovascular risk factors such as high triglycerides and high blood pressure.

Potential Biomarkers with Plasma Cortisol, Brain-derived Neurotrophic Factor and Nitrites in Patients with Acute Ischemic Stroke.

BACKGROUND: Acute Ischemic Stroke (AIS) represents an economic challenge for health systems all over the globe. Changes of neuroactive steroids have been found in different neurological diseases. We have previously demonstrated that old patients with AIS show changes of plasma cortisol and estradiol concentrations, in that increased steroid levels are associated with a deterioration of neurological status and a worse cognitive decline. OBJECTIVE: The present study assessed in patients with AIS if changes of behavior, Brain-Derived Neurotrophic Factor (BDNF) and Nitrites (NO-2) bear a relationship with the degree of hypercortisolism. METHODS: We recruited patients hospitalized within the first 24 hours of AIS. Subjects were divided into two groups, each one composed of 40 control subjects and 40 AIS patients, including men and women. The neurological condition was assessed using the National Institute of Health Stroke Scale (NIHSS) and the cognitive status with the Montreal Cognitive Assessment (MoCA). The emotional status was evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS), whereas the Modified Rankin Scale (MRS) was used to determine the functional condition. BDNF and NO-2 plasma levels were measured by ELISA and the Griess reaction method, respectively. RESULTS: We found that in AIS patients, increased plasma cortisol was negatively correlated with plasma BDNF and NO-2 levels, neurological condition, cognition, functional responses and emotional status, suggesting a relationship between the declines of clinical, behavioral and blood parameters with stress-induced cortisol elevation. CONCLUSION: Nitrites and BDNF may represent potential biomarkers for cortisol negative effects on the area of cerebral ischemia and penumbra, potentiating ischemic cell damage.

Patterns of Care and Temporal Trends in Ischemic Stroke Management: A Brazilian Perspective.

BACKGROUND AND PURPOSE: Demonstration of an improvement process of quality indicators in stroke care is essential to obtain certification as a primary stroke center (PSC). Our aim was to evaluate factors that influence temporal trends in quality indicators of ischemic stroke (IS) in a Brazilian hospital. METHODS: We evaluated patients discharged with IS from a tertiary hospital from January 2009 to December 2013. Ten predefined performance measures selected by the Get With the Guidelines-Stroke program were assessed. We also compared 5 quality indicators available from a secondary community hospital for the first year of the series to those found in the tertiary hospital. RESULTS: We evaluated 551 patients at the tertiary stroke center (median age 77.0 years [interquartile range 64.0-84.0]; 58.4% were men). The quality indicators that improved with time were the use of cholesterol-lowering therapy (P = .02) and stroke education (P = .04). The median composite perfect care did not consistently improve throughout the period (P = .13). After a multivariable adjustment, only thrombolytic treatment (odds ratio [OR] 2.06, P < .01), dyslipidemia (OR 2.03, P < .01), and discharge in a Joint Commission International's (JCI) visit year (OR 1.8, P < .01) remained as predictors of a perfect care index of 85% or higher. The quality indicators with worse performance (anticoagulation for atrial fibrillation and cholesterol reduction) were similar in the tertiary and secondary community hospitals. CONCLUSIONS: We found a significant improvement in some quality indicators across the years in a PSC located in Latin America. The overall perfect care measure did not improve and was influenced by being discharged in a JCI visit year, having dyslipidemia, and having undergone thrombolytic treatment.

Hippocampal and cerebellar histological changes and their behavioural repercussions caused by brain ischaemic hypoxia experimentally induced by sodium nitrite.

INTRODUCTION: Brain ischaemic hypoxia can produce severe neurological damage that leads to behavioural disorders. This research analysed the hippocampal and cerebellar histological alterations caused by brain ischaemic hypoxia experimentally induced by sodium nitrite (NaNO2) and possible direct repercussions of this hypoxia on behaviour. METHODOLOGY: An experimental study was carried out by administering 60mg/kg NaNO2 to 10 Wistar rats at 3 months of age for 15 consecutive days. Ten control rats did not receive NaNO2. To assess behavioural repercussions, the animals were evaluated in Open Field, Elevated Plus-Maze (EPM), and Forced Swim tests before and after injury to evaluate locomotion, anxiety, and depression, respectively. Markers of stress were evaluated by measuring the blood levels of cortisol, glucose, cholesterol, and lactate. The presence of hippocampal lesions was verified by histologically studying the CA1-CA4 areas. Sections of the cerebellum were also evaluated because Purkinje cells are highly sensitive to ischaemic hypoxia and may serve as markers for this process. RESULTS: The number of neurons with lesions was significantly higher in animals exposed to NaNO2 in the hippocampus areas CA2, CA3, and CA4. The cerebellum was also very vulnerable to hypoxia, presenting extensive lesion áreas. These results are correlated with the parameters of the anxiety and depression tests. CONCLUSION: NaNO2 promoted brain damage due to ischaemic hypoxia in rats. Intoxicated animals showed decreased brain weights; damage in hippocampus and cerebellum; and anxiogenic and depressive behaviour.

[Long-term effect of policosanol on the functional recovery of non-cardioembolic ischemic stroke patients: a one year study]. / Efecto a largo plazo del policosanol en la recuperacion funcional de pacientes con ictus isquemico no cardioembolico: estudio de un año.

INTRODUCTION: Stroke is a leading cause of mortality and disability. Policosanol has been effective in brain ischemia models. The aim of this study is to investigate whether policosanol, added to aspirin therapy within 30 days of stroke onset, is better than placebo + aspirine for the long-term recovery of non-cardioembolic ischemic stroke subjects. PATIENTS AND METHODS: Randomized, double-blind, placebo-controlled study. Eighty patients (mean age: 69 years) within 30 days of onset, with a modified Rankin Scale score (mRS) 2 to 4, were included. They were randomized in two groups (policosanol + aspirine or placebo + aspirine) for 12 months. RESULTS: Policosanol + aspirine decreased significantly mean mRS from the first interim check-up (1.5 months). The treatment even improved after long-term therapy. More policosanol + aspirin (87.5%) than placebo + aspirine (0%) patients achieved mRSs <= 1. Policosanol + aspirine increased significantly Barthel Index, lowered LDL-cholesterol and increased HDL-cholesterol versus placebo + aspirin. CONCLUSIONS: Long-term (12 months) administration of policosanol + aspirin given after suffering non-cardioembolic ischemic stroke was shown to be better than placebo + aspirin in improving functional outcomes when used among patients with non-cardioembolic ischemic stroke of moderate severity.

TITLE: Efecto a largo plazo del policosanol en la recuperacion funcional de pacientes con ictus isquemico no cardioembolico: estudio de un año.Introduccion. El ictus es una causa principal de mortalidad y discapacidad. El policosanol ha sido eficaz en modelos de isquemia cerebral. Este estudio investiga si el tratamiento a largo plazo con policosanol, añadido a la terapia con acido acetilsalicilico (AAS), dentro de los 30 dias posteriores a un ictus, es mejor que el placebo + AAS en la recuperacion de los pacientes. Pacientes y metodos. Estudio aleatorizado, doble ciego, controlado con placebo. Se incluyeron 80 pacientes (edad media: 69 años) que sufrieron un ictus en los 30 dias previos y con una puntuacion de 2-4 en la escala de Rankin modificada (mRS). Se distribuyeron aleatoriamente en dos grupos y recibieron policosanol + AAS o placebo + AAS durante 12 meses. Resultados. El tratamiento con policosanol + AAS disminuyo significativamente la puntuacion en la mRS desde el primer control intermedio (1,5 meses). El efecto del tratamiento incluso mejoro con la terapia a largo plazo. El numero de pacientes que alcanzaron valores de mRS menores o iguales a 1 fue superior en el grupo de policosanol + AAS (87,5%) que en el de placebo + AAS (0%). El tratamiento con policosanol + AAS aumento significativamente el indice de Barthel, disminuyo el colesterol LDL y aumento el colesterol HDL frente a placebo + AAS. Conclusiones. El tratamiento a largo plazo (12 meses) con policosanol + AAS fue mas efectivo que el tratamiento con placebo + AAS en la recuperacion funcional de los pacientes despues de sufrir un ictus isquemico no cardioembolico de moderada gravedad.

Vitamin D deficiency is associated with acute ischemic stroke, C-reactive protein, and short-term outcome.

The aim of this study was to investigate whether vitamin D deficiency (VDD) is associated with acute ischemic stroke, inflammatory markers, and short-term outcome. 168 acute ischemic stroke patients and 118 controls were included. The modified Rankin Scale (mRS) was applied up to 8 h of admission (baseline) and after three-months follow-up, and blood samples were obtained up to 24 h of admission to evaluate serum levels of 25-hydroxivitamin D [25(OH)D] and inflammatory markers. Vitamin D levels classified the individuals in sufficient (VDS ≥ 30.0 ng/mL), insufficient (VDI 20.0-29.9 ng/mL), and deficient (VDD < 20.0 ng/mL) status. Patients had lower levels of 25(OH)D, higher frequency of VDD (43.45% vs. 5.08%, OR: 16.64, 95% CI: 5.66-42.92, p < 0.001), and higher inflammatory markers than controls (p < 0.05). Patients with VDD showed increased high sensitivity C-reactive protein (hsCRP) levels than those with VDS status (p = 0.043); those with poor outcome presented with lower 25(OH)D levels than those with good outcome (p = 0.008); moreover, 25(OH)D levels were negatively correlated with mRS after three-months follow-up (r = -0.239, p = 0.005). The associations between VDD and higher hsCRP levels and between 25(OH)D levels and poor outcome at short-term in acute ischemic stroke patients suggest the important role of vitamin D in the inflammatory response and pathophysiology of this ischemic event.

Neuroactive Steroids in Acute Ischemic Stroke: Association with Cognitive, Functional, and Neurological Outcomes.

Despite several scientific and technological advances, there is no single neuroprotective treatment that can reverse the brain damage after acute ischemic stroke (AIS). Neuroactive steroids are cholesterol-derived hormones that have the ability to modulate the normal and pathologic nervous system employing genomic and nongenomic mechanisms. In this work, we first investigated if AIS affects the plasma concentration of 5 neuroactive steroids (cortisol, estradiol, progesterone, testosterone, and 3α-androstenediol glucuronide). Second, we studied if levels of circulating steroids associate with neurological, cognitive, and functional outcome in a cohort of 60- to 90 year-old male and female patients with AIS. For this purpose, we recruited patients who were hospitalized at the Emergency Room of the Central Military Hospital within the first 24 h after stroke onset. We designed 2 experimental groups, each one composed of 30 control subjects and 30 AIS patients, both males and females. The assessment of neurological deficit was performed with the NIHSS and the tests used for the functional and cognitive status were: (1) modified Rankin Scale; (2) Photo test, and (3) abbreviated Pfeiffer's mental status questionnaire. We observed a significant difference in plasma concentration of cortisol and estradiol between both experimental groups. In the AIS group, higher levels of these neuroactive steroids were associated with more pronounced neurological, cognitive and functional deficits in women compared to men. We propose that in elderly patients, high levels of circulating neuroactive steroids like cortisol and estradiol could potentiate AIS-mediated neuropathology in the ischemic and penumbra areas.

Reticulocyte count is the most important predictor of acute cerebral ischemia and high-risk transcranial Doppler in a newborn cohort of 395 children with sickle cell anemia.

Stroke is a severe clinical manifestation of sickle cell anemia (SCA). Despite the prognostic relevance of transcranial Doppler (TCD), more accurate tools to assess stroke risk in children with SCA are required. Here, we describe the effect of clinical, laboratory, and molecular features on the risk of stroke and high-risk TCD in children from the newborn cohort of Minas Gerais, Brazil. Outcomes studied were acute cerebral ischemia and high-risk TCD. Clinical and hematological data were retrieved from children's records. Genetic markers, which were known for their association with stroke risk, were genotyped by polymerase chain reaction/restriction fragment length polymorphism and sequencing. The cumulative incidence of acute cerebral ischemia by the age of 8 years was 7.4 % and that of high-risk TCD by the age of 11.5 years was 14.2 %. The final multivariate model for acute cerebral ischemia risk included high white blood cell count and reticulocyte count, acute chest syndrome rate, and the single nucleotide polymorphisms (SNPs) TEK rs489347 and TNF-α rs1800629. The model for high-risk TCD included high reticulocyte count and the SNPs TEK rs489347 and TGFBR3 rs284875. Children with risk factors should be considered for intensive risk monitoring and for intervention therapy.

Sleep restriction reduces the survival time and aggravates the neurological dysfunction and memory impairments in an animal model of cerebral hypoperfusion.

Cerebral blood flow is associated with the cerebrovascular prognosis. Sleep restriction (SR) may be a limiting factor of the prognosis after a cerebrovascular event, impairing the neurological recovery. We aimed to investigate the effects of SR on mortality rate and on behavioral and histological parameters of animals submitted to permanent cerebral hypoperfusion. Sixty male Wistar rats were distributed in 4 groups, according to the protocol of common carotid artery occlusion (CCAO) and SR: nSR+nCCAO, SR+nCCAO, nSR+CCAO, and SR+CCAO. The groups SR+nCCAO and SR+CCAO were submitted to SR during 10 days. The cerebral hypoperfusion was induced by the permanent CCAO. Neurological function and memory were assessed over 14 days of cerebral hypoperfusion. Analysis of neuropathological alterations were performed in the CA1 region of hippocampus. The mortality rate was 40% in the nSR+CCAO and SR+CCAO groups. SR significantly reduced the survival time of animals submitted to CCAO. After 7 and 14 days of cerebral hypoperfusion, 11% and 33% of the nSR+CCAO and SR+CCAO animals showed severe neurological dysfunction, respectively. A significant association between a high frequency of memory impairments with the group SR+CCAO was observed. The neuropathological alterations in CA1 region of hippocampus were similar among the groups. SR potentiates the negative effects of cerebral hypoperfusion conditions, suggesting that SR could be a factor associated with a worse prognosis after a cerebrovascular event.