Diferencias cliniconeurológicas en pacientes con enfermedad cerebrovascular isquémica de edades menores y mayores de 65 años

Introducción: La enfermedad cerebrovascular isquémica tiene una alta frecuencia debida, fundamentalmente, al envejecimiento poblacional. Objetivo: Comparar las características clínicas de pacientes con enfermedad cerebrovascular isquémica de dos grupos etarios. Métodos: Se realizó un estudio descriptivo, transversal y retrospectivo en 36 pacientes con enfermedad cerebrovascular isquémica correspondientes a dos grupos etarios (65 y menos años y mayores de 65), quienes fueron atendidos en el Instituto de Neurología y Neurocirugía, La Habana, de enero a diciembre del 2017. Al respecto, se analizaron variables demográficas y clínicas y se aplicaron diferentes pruebas estadísticas para comparar. Resultados: Se obtuvo un aumento significativo de pacientes hipertensos (88,9 %) en el grupo etario mayor de 65 años. La mediana de la escala de ictus del National Institute of Health fue superior en estos pacientes (mediana [10-90 percentil]: 9,5 (4-19]). Hubo incremento estadístico de los mayores de 65 años con parálisis parcial de la mirada y ataxia; en tanto, la monoparesia y la extinción visual predominaron en los de 65 y menos años. Dicha escala mostró un aumento estadístico en el ictus aterotrombótico y cardioembólico en comparación con otras causas en ambos grupos. Los pacientes mayores de 65 años con solo un factor de riesgo o ninguno y los que eran hipertensos tuvieron mayor puntuación de la escala. Conclusiones: El grado de afectación neurológica fue superior en los mayores de 65 años que tenían un factor de riesgo y en aquellos con hipertensión arterial. Puede sugerirse que los mecanismos moleculares y fisiopatológicos de estos pacientes varían según la edad.

Introduction: The ischemic cerebrovascular disease has a high frequency due to the population aging mainly. Objective: To compare clinical characteristics of patients with ischemic cerebrovascular of two age groups. Methods: A descriptive, cross-sectional, retrospective study was carried out in the Neurology and Neurosurgery Institute in Havana, from January to December, 2017 in patients with ischemic cerebrovascular disease; 36 individuals of both age groups. In this regard, demographic variables, risk factors, clinical manifestations, coma scale and neurological deficiency, etiology and localization of the ischemic ictus were analyzed. Results: The 65 years group had a significant increase of hypertensive patients (88.9%). The average of the National Institute of Health stroke scale was superior in these patients (median [10-90 percentile]: 9.5 [4-19]). There was statistical increment of over 65 years patients with partial paralysis of the look and ataxia, but monoparesis and visual extinction in the age under 65 years. Such a scale had a statistical increase in the atherothrombotic and cardioembolic ictus in comparison with other etiologies in both patient groups. The over 65 years patients with just one risk factor or and those with hypertension had a higher punctuation of the scale. Conclusions: The degree of neurological affectation was higher in over 65 years patients that had a risk factor and in those with hypertension. As a result it could be suggested that the molecular and pathophysiolologic mechanisms of these patients vary with the age.

Neuroprotective effects of the combined treatment of resveratrol and urapidil in experimental cerebral ischemia-reperfusion injury in rats

ABSTRACT Purpose: To evaluate the neuroprotective effect of resveratrol, urapidil, and a combined administration of these drugs against middle cerebral artery occlusion (MCAO) induced ischemia/reperfusion (IR) injury model in rats. Methods: Thirty-five rats were divided into five groups of seven animals each. Animals in IR, IR resveratrol (IRr), IR urapidil (IRu), and IR + combination of resveratrol and urapidil (IRc) were exposed to MCAO induced cerebral ischemia reperfusion injury model. Rats in IRr and IRu groups received 30-mg/kg resveratrol and 5-mg/kg urapidil respectively. Animals in IRc received a combined treatment of both drugs. At the end of the study, brain tissues were used for oxidative stress (malondialdehyde, glutathione, and superoxide dismutase), pro-apoptotic caspase-3, anti-apoptotic Bcl-2, and pro-inflammatory tumor necrosis factor-α cytokine level measurements. Results: The MCAO model successfully replicated IR injury with significant histopathological changes, elevated tissue oxidative stress, and upregulated apoptotic and inflammatory protein expression in IR group compared to control group (p < 0.001). All parameters were significantly alleviated in IRr group compared to IR group (all p < 0.05). In IRu group, all parameters except for caspase-3 and Bcl-2 were also significantly different than IR group (all p < 0.05). The IRc group showed the biggest difference compared to IR group in all parameters (all p < 0.001). The IRc had higher superoxide dismutase and Bcl-2 levels, and lower caspase-3 levels compared to both IRr and IRu groups (all p < 0.05). Also, the IRc group had lower MDA and TNF-α levels compared to IRu group (all p < 0.05). Conclusions: The results indicate that combined treatment of resveratrol and urapidil may be a novel strategy to downregulate neurodegeneration in cerebral IR injury.

Effect of atorvastatin preconditioning on hyperglycemia induced hemorrhagic transformation in mice after cerebral ischemia / 中华老年心脑血管病杂志

Objective To investigate the role and underlying mechanism of atorvastatin on hyper-glycemia induced hemorrhagic transformation(HT)in a mouse model of cerebral ischemia.Meth-ods A total of 36 SPF-grade male C57BL/6 mice were randomly divided into sham operation group,HT model group and atorvastatin group,with 12 mice in each group.HE staining was used to observe cerebral hemorrhage,immunofluorescent staining was employed to detect the integrity of blood-brain barrier,and Western blotting was applied to measure the protein expression of IgG,ZO-1,occludin,claduin5,MMP-2 and-9 in ischemic penumbra brain tissues.Results Com-pared with sham operation group,the neurological deficit score,mortality rate,HT incidence,HT grading score,IgG fluorescence intensity,and protein levels of IgG,MMP-2 and-9 were signifi-cantly increased,while the protein levels of ZO-1,occludin and claudin5 were obviously decreased in the HT model group(P＜0.01).Atorvastatin treatment resulted in significantly lower neuro-logical deficit score(2.73±1.19 vs 3.91±0.94),mortality rate(16.7％vs 41.6％),HT incidence(58.3％vs 91.6％),HT grading score(1.00±1.04 vs 2.58±1.13),IgG fluorescence intensity(504.30±105.52 a.u vs 859.91±153.28 a.u),and protein levels of IgG(4.55±1.40 vs 12.06± 3.73),MMP-2(1.87±0.41 vs 2.95±0.68)and-9(1.47±0.24 vs 2.12±0.23)(P＜0.05,P＜0.01),and increased protein levels of ZO-1(1.55±0.20 vs 0.53±0.10),occludin(0.92±0.11 vs 0.35±0.07)and claudin5(0.58±0.04 vs 0.30±0.05)(P＜0.01)when compared with the HT model group.Conclusion Atorvastatin can reduce the permeability of blood-brain barrier by in-hibiting the activation of MMP-2 and MMP-9 and up-regulating the protein levels of ZO-1,occlu-din and claudin5,and thus attenuate hyperglycemia-induced HT.

Research progress of influencing factors of poststroke cognitive impairment / 中华全科医师杂志

Poststroke cognitive impairment (PSCI) is a common complication after ischemic stroke, which seriously affects the recovery of neurologic function and lowers the quality of daily life of patients. In a considerable portion of patients, the PSCI is reversible. This article reviews the influencing factors of cognitive impairment after ischemic stroke, including genetic predisposition, demographic factors, lifestyles, clinical manifestations, imaging findings and drug administration, etc. to provide references for prevention and intervention of PSCI.

Correlation between tomographic scales and vasospasm and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage / Correlación entre escalas tomográficas y vasoespasmo e isquemia cerebral diferida en la hemorragia subaracnoidea aneurismática

ABSTRACT Objective: To determine the prevalence of sonographic vasospasm and delayed ischemic deficit in patients with aneurysmal subarachnoid hemorrhage, to evaluate the correlation between different tomographic scales and these complications, and to study prognostic factors in this group of patients. Methods: This was a prospective study of patients admitted to the intensive care unit with a diagnosis of aneurysmal subarachnoid hemorrhage. The prevalence of sonographic vasospasm and radiological delayed cerebral ischemia was analyzed, as was the correlation between different tomographic scales and these complications. Results: A total of 57 patients were studied. Sixty percent of the patients developed sonographic vasospasm, which was significantly associated with delayed cerebral ischemia and mortality. The Claassen and Hijdra scales were better correlated with the development of cerebral vasospasm (areas under the curve of 0.78 and 0.68) than was Fisher's scale (0.62). Thirty-two patients (56.1%) developed cerebral infarction on CT; the significantly associated factors were poor clinical grade at admission (p = 0.04), sonographic vasospasm (p = 0.008) and severity of vasospasm (p = 0.015). Only the semiquantitative Hijdra scale was significantly correlated with the development of radiological delayed cerebral ischemia (p = 0.009). The patients who presented cerebral infarction had worse neurological evolution and higher mortality. Conclusion: This is the first study in our environment on the subject. The Claassen and Hijdra tomographic scales showed better prognostic performance than the Fisher scale for the development of cerebral vasospasm. The finding of sonographic vasospasm could be a noninvasive criterion for the early detection of delayed cerebral ischemia and neurological deterioration in patients with aneurysmal subarachnoid hemorrhage.

RESUMO Objetivo: Determinar la prevalencia de vasoespasmo sonográfico y déficit isquémico diferido en pacientes con hemorragia subaracnoidea aneurismática, evaluar la correlación entre las diferentes escalas tomográficas con dichas complicaciones, así como estudiar los factores pronósticos en este grupo de pacientes. Métodos: Estudio prospectivo de pacientes ingresados a la unidad de cuidados intensivos con diagnóstico de hemorragia subaracnoidea aneurismática. Se analizó la prevalencia de vasoespasmo sonográfico e isquemia cerebral diferida radiológica, así como la correlación entre diferentes escalas tomográficas con dichas complicaciones. Resultados: Se estudiaron 57 pacientes. El 60% de los pacientes desarrollaron vasoespasmo sonográfico, el cual se asoció significativamente con isquemia cerebral diferida y mortalidad. Las escalas de Claassen y de Hijdra tuvieron una mejor correlación con el desarrollo de vasoespasmo cerebral (área bajo la curva de 0,78 y 0,68) que la de Fisher (0,62). Treinta y dos pacientes (56,1%) desarrollaron infarto cerebral en la TC, siendo los factores que se asociaron en forma estadísticamente significativa al mismo: pobre grado clínico al ingreso (p = 0,04), vasoespasmo sonográfico (p = 0,008) y severidad del vasoespasmo (p = 0,015). Solamente la escala semicuantitativa de Hijdra se correlacionó significativamente con el desarrollo de isquemia cerebral diferida radiológica (p = 0,009). Los pacientes que presentaron infarto cerebral tuvieron peor evolución neurológica y mayor mortalidad. Conclusion: Se presenta el primer estudio en nuestro medio sobre el tema. Las escalas tomográficas de Claassen y Hijdra presentaron un mejor rendimiento pronóstico que la de Fisher para desarrollo de vasoespasmo cerebral. El hallazgo de vasoespasmo sonográfico podría ser un criterio no invasivo de detección temprana de isquemia cerebral diferida y peoría neurológica en los pacientes con hemorragia subaracnoidea aneurismática.

Cerebrovascular mortality: trend and seasonality in Brazilian capitals, 2000-2019 / Mortalidade cerebrovascular: tendência e sazonalidade nas capitais brasileiras, 2000-2019

ABSTRACT OBJECTIVE To evaluate the trend and seasonality of cerebrovascular mortality rates in the adult population of Brazilian capitals from 2000 to 2019. METHODS This is an ecological and descriptive study of a time series of mortality due to cerebrovascular causes in adults (≥ 18 years) living in Brazilian capitals from 2000 to 2019, based on the Brazilian Mortality Information System. Descriptive statistical techniques were applied in the exploratory analysis of data and in the summary of specific, standardized rates and ratios by sociodemographic characteristics. The jointpoint regression model was used to estimate the trend of cerebrovascular mortality rates by gender, age groups, and geographic regions. The seasonal variability of rates by geographic regions was estimated using the generalized additive model by smoothing cubic splines. RESULTS People aged over 60 years comprised 77% of all cerebrovascular deaths. Women (52%), white individuals (47%), single people (59%), and those with low schooling (57%, elementary school) predominated in our sample. Recife (20/1,000 inhab.) and Vitória (16/1,000 inhab.) showed the highest crude mortality rates. Recife (49/10,000 inhab.) and Palmas (47/10,000 inhab.) prevailed after we applied standardized rates. Cerebrovascular mortality rates in Brazil show a favorable declining trend for adults of all genders. Seasonality influenced rate increase from July to August in almost all region capitals, except in the North, which rose in March, April, and May. CONCLUSIONS Deaths due to cerebrovascular causes prevailed in older single adults with low schooling. The trend showed a tendency to decline and winter, the greatest risk. Regional differences can support decision-makers in implementing public policies to reduce cerebrovascular mortality.

RESUMO OBJETIVO Avaliar a tendência e a sazonalidade das taxas de mortalidade cerebrovascular na população adulta das capitais brasileiras de 2000 a 2019. MÉTODOS Estudo ecológico e descritivo de séries temporais de mortalidade por causas cerebrovasculares em adultos (≥ 18 anos) residentes nas capitais do Brasil no período 2000-2019, obtidas do Sistema de Informações sobre Mortalidade. Técnicas de estatística descritiva foram aplicadas na análise exploratória dos dados e no resumo de taxas específicas, padronizadas e razões por características sociodemográficas. A regressão de pontos de junção (jointpoint regression model) estimou a tendência das taxas de mortalidade cerebrovascular por sexo, grupos etários e regiões geográficas. A variabilidade sazonal por regiões geográficas das taxas foi estimada utilizando o modelo aditivo generalizado por meio de splines de suavização cúbica. RESULTADOS As pessoas maiores de 60 anos representaram 77% dos óbitos cerebrovasculares. Predominaram o sexo feminino (52%), a raça branca (47%), os solteiros (59%) e a baixa escolaridade (57%, ensino fundamental). As capitais Recife (20/1.000 hab.) e Vitória (16/1.000 hab.) apresentaram as maiores taxas brutas de mortalidade. Aplicando as taxas padronizadas Recife (49/10.000 hab.) e Palmas (47/10.000 hab.) prevaleceram. As taxas de mortalidade cerebrovascular no Brasil apresentam uma tendência favorável ao declínio em ambos os sexos e em adultos. A sazonalidade mostrou influenciar na elevação das taxas entre os meses de julho a agosto em quase todas as capitais das regiões, exceto na Norte, que se elevaram nos meses de março, abril e maio. CONCLUSÕES Os óbitos por causa cerebrovascular prevaleceram em pessoas idosas, solteiras e com baixa escolaridade. A tendência foi favorável ao declínio, sendo o inverno o período de maior risco. As diferenças regionais permitem subsidiar os tomadores de decisões em relação à implementação de políticas públicas para reduzir a mortalidade cerebrovascular.

Naringenin attenuates cerebral ischemia/reperfusion injury by inhibiting oxidative stress and inflammatory response via the activation of SIRT1/FOXO1 signaling pathway in vitro

Purpose: To explore the protection of naringenin against oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT22 cell injury, a cell model of cerebral ischemia/reperfusion (I/R) injury in vitro, focusing on SIRT1/FOXO1 signaling pathway. Methods: Cytotoxicity, apoptosis, reactive oxygen species (ROS) generation, malondialdehyde (MDA) content, 4-hydroxynonenoic acid (4-HNE) level, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were measured by commercial kits. Inflammatory cytokines levels were determined by enzyme-linked immunosorbent assay (ELISA). The protein expressions were monitored by Western blot analysis. Results: Naringenin significantly ameliorated OGD/Rinduced cytotoxicity and apoptosis in HT22 cells. Meanwhile, naringenin promoted SIRT1 and FOXO1 protein expressions in OGD/R-subjected HT22 cells. In addition, naringenin attenuated OGD/R-induced cytotoxicity, apoptosis, oxidative stress (the increased ROS, MDA and 4-HNE levels, and the decreased SOD, GSH-Px and CAT activities) and inflammatory response (the increased tumor necrosis factor-α, interleukin [IL]-1ß, and IL-6 levels and the decreased IL-10 level), which were blocked by the inhibition of the SIRT1/FOXO1 signaling pathway induced by SIRT1-siRNA transfection. Conclusion: Naringenin protected HT22 cells against OGD/R injury depending on its antioxidant and anti-inflammatory activities via promoting the SIRT1/FOXO1 signaling pathway.

Fasudil mediates neuroprotection in ischemia/reperfusion by modulating the ROCK-PPARα-NOX axis

Purpose: Cerebral ischemia-reperfusion (I/R) is a neurovascular disorder that leads to brain injury. In mice, Fasudil improves nerve injury induced by I/R. However, it is unclear if this is mediated by increased peroxisome proliferator-activated receptor-α (PPARα) expression and reduced oxidative damage. This study aimed to investigate the neuroprotective mechanism of action of Fasudil. Methods: MCAO (Middle cerebral artery occlusion) was performed in male C57BL/6J wild-type and PPARα KO mice between September 2021 to April 2023. Mice were treated with Fasudil and saline; 2,3,5-Triphenyltetrazolium chloride (TTC) staining was performed to analyze cerebral infarction. PPARα and Rho-associated protein kinase (ROCK) expression were detected using Western blot, and the expression of NADPH subunit Nox2 mRNA was detected using real-time polymerase chain reaction. The NADPH oxidase activity level and reactive oxygen species (ROS) content were also investigated. Results: After cerebral ischemia, the volume of cerebral necrosis was reduced in wild-type mice treated with Fasudil. The expression of PPARα was increased, while ROCK was decreased. Nox2 mRNA expression, NADPH oxidase activity, and ROS content decreased. There were no significant changes in cerebral necrosis volumes, NADPH oxidase activity, and ROS content in the PPARα KO mice treated with Fasudil. Conclusions: In mice, the neuroprotective effect of Fasudil depends on the expression of PPARα induced by ROCK-PPARα-NOX axis-mediated reduction in ROS and associated oxidative damage.

Predictive value of combined three serum cytokine levels for delayed cerebral ischemia in patients after aSAH / 中华老年心脑血管病杂志

Objective To investigate the predictive value of soluble tyrosine kinase-1(sFlt-1),chiti-nase protein 40(YKL-40)and lipoprotein phospholipase A2(Lp-PLA2)for delayed cerebral is-chemia(DCI)in patients after aneurysmal subarachnoid hemorrhage(aSAH).Methods A total of 100 aSAH patients treated in Department of Neurology of Nanyang First People's Hospital from January 2018 to December 2022 were enrolled,and then divided into DCI group(n=31)and non-DCI group(n=69).The levels of sFlt-1,YKL-40,and Lp-PLA2 in the serum were detected.ROC curve was plotted to evaluate the predictive value of serum sFlt-1,YKL-40 and Lp-PLA2 levels for DCI after aSAH.Results The serum levels of sFlt-1,YKL-40 and Lp-PLA2 were high-er in the DCI group than the non-DCI group(0.13±0.02 g/L vs 0.07±0.01 g/L,292.65±78.60μg/L vs 206.33±59.28 μg/L,396.59±41.12 μg/L vs 281.19±66.02 μg/L,P＜0.01).Logistic re-gression analysis revealed that elevated levels of sFlt-1,YKL-40 and Lp-PLA2,Hunt-Hess grade ≥3,modified Fisher grade ≥3,and WFNS grade ≥3 were risk factors for DCI after aSAH.ROC curve analysis showed that the AUC values of serum sFlt-1,YKL-40 and Lp-PLA2 levels in predicting DCI after aSAH was 0.806,0.789 and 0.893,respectively,and the value was 0.950 when the three indicators combined together.Conclusion Serum sFlt-1,Lp-PLA2 and YKL-40 levels are all elevated in the aSAH patients with DCI,and their combined detection is helpful for diagno-sing the occurrence of DCI after aSAH.

Effects of the enriched environment on pyroptosis in rats with cerebral ischemia-reperfusion injury / 中华老年医学杂志

Objective:To explore the effect of the enriched environment(EE)on pyroptosis in rats with cerebral ischemia-reperfusion injury(CIRI).Methods:45 male Sprague-Dawley rats were randomly divided into three groups: a sham surgery(Sham)group, a cerebral ischemia-reperfusion(CIR)group and an enriched environment(EE)group, with 15 rats in each group.Except for the Sham group, the right middle cerebral artery occlusion model was established in the other two groups.After surgery, the EE group was fed in EE, and the other two groups were fed in standard environment.All the rats were assessed using the modified neurological severity score(mNSS)before modeling and on the 1st day, 7th day and 14th day following surgery.On the 14th day after surgery, 2, 3, 5-triphenyltetrazolium chloride(TTC)staining was used to evaluate the infarct volume, hematoxylin and eosin(HE)staining was used to examine pathomorphological changes of the hippocampal CA1 region on the ischemic side of the rats in each group, immunohistochemical assay was used to detect the expression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)and cysteinyl aspartate specific proteinase-1(caspase-1)proteins in the CA1 region, and ultrastructural changes in neurons in the CA1 region were observed under transmission electron microscopy.Results:Compared with the Sham group, the mNSS scores of the CIR group and the EE group were significantly higher on the 1st day and 7th day after surgery( P<0.05), but there was no significant difference between the CIR and EE groups( P>0.05). On the 14th day after surgery, compared with the CIR group, the EE group showed a decrease in the mNSS score and the cerebral infarct volume( P<0.05), alleviated pathomorphological changes, decreased expression of NLRP3 and caspase-1 proteins( P<0.05), and alleviated pathological changes of pyroptosis in the ultrastructure of neurons. Conclusions:EE can reduce the damage of neurological function, reduce the cerebral infarct volume, and play a protective role for the brain in CIRI rats.The mechanism may be related to the down-regulation of the expression of NLRP3 and caspase-1 proteins related to the classical pyroptosis pathway, leading to the inhibition of pyroptosis.

Predictive value of plasma exosomal miR-124-3p for the risk of chronic cerebral hypoperfusion / 中华内科杂志

Objective:To investigate the predictive value of plasma exosomal microRNA (miR)-124-3p in the risk of chronic cerebral hypoperfusion (CCH).Methods:A case-control study. Thirty patients who were diagnosed with CCH (CCH group) based on cranial artery spin labeling (ASL) in the neurology outpatient clinic of Sichuan Provincial People′s Hospital from March 2022 to June 2022 and 30 healthy volunteers (control group) were included. Age, gender, smoking history, alcohol consumption history, diabetes history, hypertension, hyperlipidemia history, uric acid, fasting blood glucose, homocysteine and plasma exosomal miR-124-3p expression level were compared between the two groups. Comparisons of categorical variables were analyzed by either χ2 test or Fisher′s exact test. If the data of continuous variables followed a normal distribution, they were expressed as mean±standard deviation (SD) and compared by t-test for two independent samples; otherwise, the data were expressed as M( Q1, Q3), and analyzed by Mann-Whitney U test for comparison between two groups. The correlation between cerebral blood flow and exosomal miR-124-3p levels was analyzed by Pearson′s correlation. Binary multifactorial logistic regression analysis was used to determine the risk factors associated with CCH, and corresponding odds ratios ( OR) and 95% confidence intervals ( CI) were calculated. P<0.05 was considered significant. Results:There was no significant difference in age (64±8 vs. 60±8 years old), gender (33.3% vs. 30.0%), history of smoking (20.0% vs. 3.3%), alcohol consumption (20.0% vs. 6.7%), diabetes mellitus (13.3% vs. 13.3%), hypertension (53.3% vs. 30.0%), history of hyperlipidemia (46.7% vs. 36.7%), uric acid (288±60 vs.319±67 μmol/L), and fasting glucose [4.99(4.63, 5.91) vs. 5.28(5.09, 6.05) mmol/L] and homocysteine [11.35(10.18, 13.08) vs.11.00(9.78, 13.03) μmol/L] between the CCH and control groups ( P>0.05). Plasma exosomal miR-124-3p expression was significantly higher in the CCH group than in the control group [13.08 (8.59, 21.55) vs. 2.85 (1.44, 5.10), respectively; U=169.50, P<0.001]. Pearson′s correlation test showed that the level of exosomal miR-124-3p was negatively correlated with cerebral blood flow in the hypoperfused region in patients with CCH ( r=-0.932, P<0.001). Multi-factor logistic regression analysis showed that plasma exosomal miR-124-3p was independently associated with the risk of CCH ( OR=1.169,95% CI 1.063-1.286, P=0.001). Conclusions:The expression of plasma exosomal miR-124-3p is negatively correlated with cerebral blood flow in areas of low perfusion and is an independent risk factor for CCH. Plasma exosomal miR-124-3p may thus serve as a valid biomarker for CCH risk prediction.

Efficacy and safety of endovascular therapy after 24 h from ischemic stroke onset in patients with acute anterior circulation ischemic stroke / 中华内科杂志

Objective:To explore the effectiveness and safety of endovascular treatment (EVT) for patients with acute anterior circulation ischemic stroke with symptom onset exceeding 24 h.Methods:In this retrospective cohort study, data were extracted from patients who underwent endovascular treatment for acute anterior circulation ischemic stroke at the First Hospital of Jilin University from February 2019 to April 2022. A total of 569 patients were included, with a mean age of 63 (54-70) years. Among them, 398 (69.9%) were male. The patients were divided into two groups based on symptom onset time:>24 h group and≤24 h group. Propensity score matching (PSM) was used to match the patients in a 1︰1 ratio between the>24 h group and the≤24 h group. Logistic regression was used to evaluate the impact of symptom onset time on outcome events.Results:Before PSM, compared with≤24 h group, the>24 h group had a younger age [56 (48, 64) vs. 64 (55, 70), Z=-3. 60, P<0.001]; lower proportion of prior atrial fibrillation [1.8% (1/57) vs. 21.1% (108/512), χ2=12.39, P<0.001]; lower proportion of wake-up stroke [7.0% (4/57) vs. 27.7% (142/512), χ2=11.54, P<0.001]; lower baseline NIHSS score [11.0 (7.5, 14.0) vs. 13.0 (10.0, 16.0), Z=-3.22, P<0.001]; and a higher American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology(ASITN/SIR) grading ( P<0.001). After PSM, there were no significant differences in baseline characteristics between the two groups. There was no significant difference in the proportion of patients with a modified Rankin Scale (mRS) score≤2 at 90 days after surgery between the two groups (before matching: 42.0% vs. 40.4%, OR=0.745, 95% CI 0.407-1.362, P=0.339; after matching: 51.8% vs. 39.3%, OR=0.511, 95% CI 0.212-1.236, P=0.136). No significant differences were observed in the incidence of any safety outcomes between the>24 h group and the≤24 h group. Conclusion:For patients with acute anterior circulation ischemic stroke with symptom onset exceeding 24 h, EVT is feasible after strict radiological screening and has similar safety and effectiveness as for patients with symptom onset under 24 h.

Clinical features and management of ischemic stroke during pregnancy and puerperium / 中华围产医学杂志

Objective:To investigate the clinical features and treatment strategies of ischemic stroke during pregnancy and puerperium.Methods:This study retrospectively analyzed the clinical data of six women diagnosed with ischemic stroke during pregnancy and puerperium by cranial CT or MRI at the Second Affiliated Hospital of Shandong First Medical University from January 2013 to December 2021. Descriptive data analysis was performed.Results:There were 31 082 deliveries at the hospital in this period. The incidence of ischemic stroke during pregnancy and puerperium was 0.019% (6/31 082) during the study period. Among the six patients, three occurred in early pregnancy, one in late pregnancy, and two in the puerperium. The most common symptoms included headache, nausea, vomiting, blurred vision, convulsions, and limb movement disorders. All six patients received conservative treatment. Two term neonates were born vaginally, and one preterm infant was delivered by cesarean section. None of the three babies had any significant malformations or abnormalities in growth and development. Two pregnancies were terminated, and one received a medical abortion due to a missed abortion after embryo arrest.Conclusions:Symptoms of ischemic stroke during pregnancy and puerperium are atypical. The treatment should be individualized based on a comprehensive assessment of the etiology, severity, and maternal and fetal conditions. Maternal and fetal conditions and gestational weeks should be considered in obstetric management.

Experimental study on the improvement of inflammatory response in rats with cerebral ischemia by Chinese ultrasound drug permeation electrotherapy device / 国际中医中药杂志

Objective:To observe the effects of Traditional Chinese Medicine (TCM)ultrasound drug permeation electrotherapy device on the inflammatory response of rats with cerebral ischemia, and to provide an experimental basis for the clinical application of TCM ultrasound drug permeation electrotherapy device in the treatment of cerebral ischemia.Methods:A total of 72 SD rats were randomly divided into sham-operation group (12 rats) and modeling group (60 rats). The middle cerebral artery occlusion (MCAO) model was prepared by thread embolism in the model group. The rats were divided into model group, Chinese medicine tablet group, blank tablet + TCM ultrasound drug permeation electrotherapy group (hereinafter referred to as "blank tablet + electrotherapy group"), Chinese medicine tablet + TCM ultrasound drug permeation electrotherapy group (hereinafter referred to as "Chinese medicine tablet + electrotherapy group") and butylphthalide group according to the random number table method, with 12 rats in each group. The corresponding treatment was given continuously for 7 days. The neurological function was scored using Longa method evaluation criteria; TTC staining was used to observe the infarct volume and calculate the percentage of infarct volume; HE staining was used to observe the cell morphology of cortical area in each group of rats; ELISA was used to detect the serum TNF-α and IL-1β levels in each group of rats; TLR4, MyD88 and NF-κBp65 protein expressions in hippocampal tissue of each group of rats on the infarct side were detected by Western blot method.Results:Compared with the model group, the neurological function scores of rats in the blank tablet + electrotherapy group, the herbal tablet + electrotherapy group, and the butylphthalein group significantly decreased ( P<0.05), the percentage of cerebral infarct volume significantly decreased ( P<0.05), the contents of serum TNF-α and IL-1β significantly decreased ( P<0.05), and the expressions of TLR4 (0.42±0.07, 0.31±0.07, 0.19±0.04 vs. 0.68±0.14), MyD88 (0.39±0.12, 0.30±0.07, 0.23±0.11 vs. 0.67±0.10), NF-κBp65 (0.32±0.03, 0.27±0.02, 0.17±0.03 vs. 0.57±0.12) protein in hippocampal tissue significantly decreased ( P<0.05). Conclusion:The TCM ultrasound drug permeation electrotherapy device can inhibit TLR4, MyD88, NF-κBp65 protein expressions and reduce the release of serum inflammatory factors TNF-α and IL-1β, thus exerting cerebral ischemic protective effects.

Study on the mechanism of Tanhuo Prescription in the regulation of M1-type microglia activation and reducing the damage of brain tissue in rats with cerebral ischemia / 国际中医中药杂志

Objective:To observe the effect and mechanism of Tanhuo Prescription on regulating the activation of M1 microglia and alleviating brain tissue injury in rats with cerebral ischemia.Methods:Male SD rats were divided into sham-operation group, model group, Tanhuo Prescription high-(3.68 g/kg), medium-(1.84 g/kg), low-dosage(0.92 g/kg) groups, and ginaton group (0.06 g/kg) using random number table method. Except for the sham-operation group, the other groups established cerebral ischemia rat models using the middle cerebral artery occlusion method. The balance beam walking test was used to evaluate the symptoms of neurological deficit. MRI-T2 mapping was used to measure the damage to brain tissue. LFB staining was used to observe the damage to nerve fibers. HE staining was used to observe the damage to nerve cell, and Iba-1 and CD16/Iba-1 immunofluorescence staining were used to observe the condition of microglial activation.Results:Compared with the model group, the scores of balance beam walking ability of rats in Tanhuo Prescription high-dose group and ginaton group at 24 h, 48 h and 72 h after ischemia were significantly improved ( P<0.05, P<0.01). The scores of balance beam walking ability of rats in Tanhuo Prescription low- and medium- dose groups at 72 h after ischemia were improved ( P<0.01). Compared with the model group, the T2 values of the cortex and striatum around the infarct of rats in Tanhuo Prescription high-dose group and ginaton group were significantly reduced ( P<0.05, P<0.01), and the T2 values of the striatum around the infarct of rats in Tanhuo Prescription low- and medium- dose groups were significantly reduced ( P<0.05). Compared with the model group, the LFB IOD of the cortex, striatum and outer capsule around the infarct decreased in the Tanhuo Prescription high-,low-dose group and ginaton group ( P<0.01). The LFB IOD of striatum around infarct decreased in medium- dose Tanhuo Prescription group ( P<0.01). Compared with the model group, the pathological injury degree of the striatum around the infarct of rats in Tanhuo Prescription low- ,medium-, and high-dose groups decreased, and the cell density decreased ( P<0.05, P<0.01). The density of the cortical and striatum cells around the infarct of rats in ginaton group increased ( P<0.01, P<0.05). Compared with the model group, the number of Iba-1 and CD16/Iba-1 positive cells in the cortex and striatum around the infarct decreased in Tanhuo Prescription medium-, high-dose and ginaton groups ( P<0.01). The number of CD16/Iba-1 positive cells in the cortex and striatum around the infarct of rats in Tanhuo Prescription low-dose group decreased ( P<0.01), and the number of Iba-1 positive cells in the striatum around the infarct of rats in Tanhuo Prescription low-dose group decreased ( P<0.01). Conclusion:Tanhuo Prescription can improve the symptoms of neurological deficits in rats with cerebral ischemia, reduce the neuropathological damage in the cerebral area around ischemic infarction, and inhibit the activation of M1 microglia.

The safety and efficiency of left atrial appendage closure combined delayed anticoagulant therapy in atrial fibrillation patients combined with cardiogenic stroke during anticoagulant therapy / 中国医师进修杂志

Objective:To assess the safety and efficiency of left atrial appendage closure (LAAC) combined delayed anticoagulant therapy in atrial fibrillation (AF) patients combined with cardiogenic stroke during anticoagulant therapy.Methods:Using prospective research methods, 35 AF patients combined with cardiogenic stroke during anticoagulant therapy from September 2020 to June 2022 in Xuanwu Hospital, Capital Medical University were selected. All patients were treated with LAAC and delayed anticoagulant therapy. The endpoints were the safety and efficacy of LAAC combined with delayed anticoagulant therapy. The primary endpoint of efficacy was the composite endpoint of postoperative death, myocardial infarction, hemorrhagic stroke and systemic embolism. The safety endpoint was major bleeding as defined by the International Society for Thrombosis and Hemostasis and clinically relevant non-major bleeding.Results:Among 35 patients, 21 were males and 14 were females; the age was (68.5 ± 9.3) years old; the CHA 2DS 2-VASc score was 5 (4, 6) scores; the time to the last stroke was 95 (42, 98) d; the National Institutes of Health stroke scale score at the time of stroke was 3 (1, 6) scores. All patients successfully completed LAAC without perioperative instrument-surface thrombosis, death, new stroke or bleeding events. Thirty-two patients continued oral anticoagulant therapy 45 d after LAAC. The patients were followed up for (12.6 ± 4.3) months, 1 patient experienced recurrent ischemic stroke, 2 patients endured mucosal bleeding, there were no adverse events such as all-cause death, cardiovascular death, systemic embolism and hemorrhagic stroke. Conclusions:The LAAC combined delayed anticoagulant therapy is efficient and safe in patients with AF. For AF patients combined with cardiogenic stroke during anticoagulant therapy, LAAC combined with delayed anticoagulation therapy may be considered to further prevent ischemic stroke events.

Ischemic stroke model in large animals / 国际脑血管病杂志

Due to the failure of multiple translational researches, Stroke Therapy Academic Industry Roundtable (STAIR) recommends the use of large animal models of focal cerebral ischemia for preclinical researches. Especially, stroke treatment has currently entered a new era of vascular recanalization. Large animals commonly used in acute ischemic stroke models include dogs, swine, sheep, and non-human primates, which can be used to simulate various aspects of cerebral ischemia and reperfusion (vascular recanalization) in patients. Although large animals have significant advantages due to their proximity to humans in anatomy and physiology, there are also issues with anatomical and physiological specificity and ethical limitations. This article summarizes the large animal ischemic stroke models prepared by craniotomy and endovascular intervention, hoping to help researchers select the most appropriate large animal ischemic stroke model, and then promote the development of stroke translational research.

Carotid plaque and ischemic stroke / 国际脑血管病杂志

Carotid atherosclerosis is closely associated with ischemic stroke. Research shows that the rupture of vulnerable carotid plaque is an important reason for carotid atherosclerosis leading to thromboembolic events. Therefore, early identification of vulnerable carotid plaques is of great significance for the diagnosis, treatment, and prevention of ischemic stroke. This article reviews the pathophysiological features, imaging evaluation of carotid plaque and its relationship with ischemic stroke.

Role and mechanism of ferroptosis in ischemic brain injury / 国际脑血管病杂志

Ferroptosis is a cell death mode characterized by iron-dependent and excessive accumulation of lipid hydroperoxides, which has been discovered in recent years. Its regulatory mechanisms mainly involve iron metabolism, lipid peroxidation and amino acid metabolism. Ferroptosis is closely associated with the pathogenesis of ischemic stroke and is a promising therapeutic target for ischemic stroke. This article elaborates on the role of the main regulatory pathways of ferroptosis in ischemic stroke, providing new therapeutic ideas and targets for targeting the ferroptosis pathway to improve the outcome of ischemic stroke.

Activator protein-1 complex and ischemic stroke / 国际脑血管病杂志

The activator protein-1 (AP-1) complex is a transcription factor complex composed of Jun, Fos, activating transcription factors, and MAF protein subunits, involved in physiological and pathological processes such as cell proliferation, differentiation, apoptosis, and stress response. In recent years, research has shown that the AP-1 complex plays an important role in ischemic stroke, participating in processes such as microglial activation and neuronal apoptosis after ischemic brain injury, affecting the progression of neuroinflammation and the degree of neurological dysfunction after stroke.