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.

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.

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.

Protective effect of remote ischemic preconditioning combined with melatonin against cerebral reperfusion injury in rats and the value of multimodal MRI in evaluating the efficacy / 中华放射学杂志

Objective:To explore the possible mechanisms of remote ischemic preconditioning (RIPC) combined with melatonin (MT) against cerebral ischemia-reperfusion injury and to evaluate the value of multimodal MRI.Methods:From December 2021 to December 2022, fifty SPF-grade male SD rats were selected and divided into sham surgery group ( n=10), middle cerebral artery occlusion model group ( n=10), melatonin (MT) group ( n=10), remote ischemic preconditioning (RIPC) group ( n=10) and MT+RIPC group ( n=10). Neurological function scoring and multimodal MRI examinations, including T 2 fluid-attenuated inversion recovery (FLAIR) imaging, diffusion-weighted imaging (DWI), and arterial spin labeling (ASL) imaging, were performed on rats after surgery. After the scans, the rats were euthanized. The brain tissues of 3 rats in each group were randomly selected for HE staining and immunohistochemical staining to observe the pathological morphology of brain tissues and to validate the expression of nuclear factor-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). The remaining 6 rats were used for enzyme-linked immunosorbent assay to detect levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in brain infarction tissues. ANOVA test or Kruskal-Wallis H test was performed to compare the differences between groups. Results:There were statistically significant differences in neurological function scores and brain infarct volumes among the five groups ( P<0.001). Compared with the sham surgery group, the rats′ neurological function scores and brain infarct volumes were increased in the model group, RIPC group, MT group, and MT+RIPC group ( P<0.05); While compared with the model group, the rats′ neurological function scores and brain infarct volumes were decreased in the RIPC group, MT group, and MT+RIPC group ( P<0.05). MRI showed that abnormal signals were observed on the lesion hemisphere on the right side in rats of the four groups except for the sham surgery group. The lesions showed high signal on T 2 FLAIR and DWI, low signal on apparent diffusion coefficient map, and low perfusion on cerebral blood flow map. Pathological examination showed neuronal nuclear shrinkage in the necrotic area of the brain tissue in the model group, with surrounding neurons exhibiting edema and degeneration. In the RIPC and MT groups, edema and degeneration of neural cells around the infarction area were reduced, while the MT+RIPC group showed primarily neuronal edema with overall structural preservation. The range of Nrf2 and HO-1 protein positivity was significantly increased in the MT+RIPC group compared with the model group. The overall differences in IL-1β, TNF-α and IL-6 levels of 5 groups were statistically significant ( P<0.05), in which IL-1β, TNF-α and IL-6 levels in the model group, RIPC group, MT group, and MT+RIPC group increased compared with the sham-operated group ( P<0.05), and IL-1β, TNF-α, and IL-6 levels decreased in the RIPC group, MT group, and MT+RIPC group compared with the model group ( P<0.05). Conclusion:RIPC+MT exerts antioxidant effects through Nrf2/HO-1 pathway and also exhibits anti-inflammatory properties by reducing levels of IL-1β, IL-6, and TNF-α, thereby alleviating brain edema and neuronal damage, reducing infarct volume and improving neurological deficits in rats with cerebral artery occlusion. The multimodal MRI evaluation demonstrates the value of RIPC+MT in protecting against cerebral ischemia-reperfusion injury.

A study on the severity of brain tissue edema in acute anterior circulation ischemic stroke based on time to maximum of the residual function hemodynamic changes / 中华放射学杂志

Objective:To explore the value of the Wilcoxon-Mann-Whitney generalized dominance ratio (T max-weighted ratio) based on residual tissue time to peak (T max) delayed severity weighting in predicting the moderate to severe edema after acute anterior circulation ischemic stroke. Methods:The clinical and imaging features of patients with acute anterior circulation ischemic stroke from January 2019 to April 2022 in Yidu Central Hospital of Weifang were retrospectively analyzed. A total of 85 patients were enrolled, including 60 males and 25 females, with the age from 34 to 93 (67±11) years old. Patients underwent non-contrast CT, CT angiography of the head and neck, and CT perfusion imaging of the head, and ischemic core volume and the ratio of T max 4-6 s volume, T max 6-8 s volume, T max 8-10 s volume, and T max >10 s volume relative to the entire hypo-perfused area (T max>4 s volume) was measured, and the T max-weighted ratio was calculated, the collateral circulation were assessed. Patients were divided into mild edema group and moderate to severe edema group according to whether local swelling exceeded 1/3 of the unilateral cerebral hemisphere on non-contrast CT at 24-48 h. The indicators were compared between the two groups by independant t test, Mann-Whitney U and χ 2 test. The performance to predict moderate to severe edema was assessed using the receiver operating characteristic (ROC) curve. The univariate and multivariate logistic regression was used to analyze the risk factors for the moderate to severe edema. Differences in baseline National Institutes of Health Stroke Scale (NIHSS) score and infarct core volume were equalized by 1∶1 propensity score matching (PSM) and the differences of T max-weighted ratio between the two groups were further compared. Results:There were 52 cases in the mild edema group and 33 cases in the moderate to severe edema group. Baseline NIHSS score, T max>10 s volume, ischemic core volume, T max-weighted ratio and proportion of poor collateral circulation were higher in the moderate-severe edema group than those in the mild edema group ( P<0.001), T max 4-6 s volume was lower than in the mild edema group ( P<0.001). ROC analysis showed that the area under the curve (AUC) of T max-weighted ratio for predicting the incidence of moderate to severe edema was 0.885 (95%CI 0.798-0.944), with an optimal cut-off value of 1.17, sensitivity of 84.85% and specificity of 82.69% before PSM. The predictive ability based on T max-weighted ratio was similar to ischemic core volume( Z=0.64, P=0.520), T max 4-6 s volume ( Z=1.48, P=0.140) and superior to T max 6-8 s volume( Z=5.65, P<0.001), T max 8-10 s volume( Z=4.46, P<0.001), T max >10 s volume ( Z=2.91, P=0.004). Multivariate logistic regression analysis showed that T max-weighted ratio>1.17 was an independent predictor of the development of moderate to severe edema (OR=10.40,95%CI 2.65-40.83, P=0.001) through adjusted for baseline NIHSS score and ischemic core volume. After PSM, 14 patients in each group were included; the T max-weighted ratio was higher in the moderate-to-severe edema group than that in the mild edema group ( P<0.001), and the differences in other factors were not statistically significant (all P>0.05); ROC analysis showed that the AUC of T max-weighted ratio to predict the occurrence of moderate-to-severe edema was 0.852 (95%CI 0.667-0.957). Conclusion:The T max-weighted ratio can predict the occurrence of moderate-to-severe edema in brain tissue after acute anterior circulation ischemic stroke.

Effects of butylphthalide combined with alteplase on acute ischemic stroke / 中国基层医药

Objective:To analyze the effects of butylphthalide combined with alteplase on acute ischemic stroke.Methods:A total of 176 patients with acute ischemic stroke who received treatment at The Second People's Hospital of Liaocheng from November 2020 to October 2021 were prospectively included in this study. They were divided into control and combined treatment groups ( n = 88/group) according to hospital registraction number. The control group was given intravenous thrombolysis with alteplase. The combined treatment group was intravenously administered alteplase for 6 hours followed by butylphthalide sodium chloride injection. The two groups were treated for 2 consecutive weeks. The National Institutes of Health Stroke Scale score, clinical efficacy, interleukin-6, tumor necrosis factor-α, and high-sensitivity C-reactive protein levels as well as the incidence of adverse drug reactions were compared between the two groups. Results:After thrombolysis, the National Institutes of Health Stroke Scale score, interleukin-6, tumor necrosis factor-α, and high-sensitivity C-reactive protein levels in the combined treatment group were (4.23 ± 1.75) points, (6.42 ± 2.05) ng/L, (13.42 ± 3.59) ng/L, and (3.17 ± 0.94) mg/L, respectively, which were significantly lower than (7.28 ± 1.93) points, (9.58 ± 2.79) ng/L, (22.28 ± 3.73) ng/L, and (5.23 ± 1.25) mg/L, respectively in the control group ( t = 10.98, 20.29, 16.06, 12.36, all P < 0.001). The total response rate in the combined treatment group was significantly higher than that in the control group [94.32% (83/88) vs. 80.68% (71/88), χ2 = 7.48, P < 0.05]. There was no significant difference in the incidence of adverse drug reactions between the combined treatment and control groups [6.82% (6/88) vs. 11.36% (10/88), χ2 = 0.01, P > 0.05]. Conclusion:Butylphthalide combined with alteplase for the early treatment of acute ischemic stroke can increase therapeutic efficacy, improve neurological function, and reduce inflammatory responses. The combined therapy has a positive clinical value in the early treatment of acute ischemic stroke.

Electroacupuncture stimulation attenuates corpus striatum white matter injury in rats with cerebral ischemia by inhibition of Nogo-A/NgR pathway / 针灸推拿医学（英文版）

Objective:To investigate the effect and the mechanism of electroacupuncture(EA)on corpus striatum white matter injury in rats with focal cerebral ischemia(FCI).Methods:Forty-four specific-pathogen-free Sprague-Dawley rats were divided into a normal group(n=10),a sham-operation group(sham group,n=10),and a modeling group(n=24)using the random number table method.The normal group was a blank control.In the sham group,only the vessels and vagus nerve were isolated without embolization.The FCI rat model in the modeling group was replicated using the middle cerebral artery occlusion embolization method.The 20 successfully modeled rats were randomly divided into a model group and an EA group,with 10 rats in each group.Rats in the model group did not receive further treatment.Rats in the EA group received EA stimulation at Baihui(GV20)and the left Zusanli(ST36)24 h after the successful modeling,30 min each time,once a day for 14 d.On the 14th day of the experiment,rats in each group were scored for neurological deficits and then sacrificed,and brain tissues containing corpus striatum around the ischemic focus were paraffin-embedded from 5 rats in each group.Luxol fast blue(LFB)staining was used to detect damage changes in the white matter.The positive immunoreactive expression of myelin basic protein(MBP),myelin-associated growth inhibitor A(Nogo-A)and its receptor(NgR)in rat corpus striatum tissue was detected by immunohistochemistry staining,and then the protein expression of MBP,Nogo-A,and NgR in the corpus striatum tissue around the ischemic focus was determined by Western blotting.Results:Compared with the normal group and the sham group,the model group had a significantly higher neurological deficit score(P＜0.05)and fiber bundle injuries in the corpus striatum white matter,evidenced by a significantly lower mean optical density value of corpus striatum LFB staining(P＜0.05),a significantly lower MBP expression level(P＜0.05),and significantly higher Nogo-A and NgR protein expression levels(P＜0.05).Compared with the model group,the neurological deficit score was significantly lower(P＜0.05),the mean optical density value of LFB staining was significantly higher(P＜0.05),the MBP expression level was increased(P＜0.05),and the expression levels of Nogo-A and NgR proteins were decreased(P＜0.05)in the EA group.Conclusion:EA reduces the ischemia-induced corpus striatum white matter injury and improves neurological deficits.The mechanism may be related to the inhibition of Nogo-A/NgR activation.

Quantitative analysis of digital subtraction angiography: the way to advanced reperfusion evaluation / 中华神经科杂志

Quantitative digital subtraction angiography (DSA) analysis can obtain pixel time density curves through changes in contrast agent concentration, and calculate the corresponding parameters of the contrast agent in the area of interest, achieving semi quantitative analysis of patient hemodynamic, used to evaluate the reperfusion status of intravascular therapy in patients with acute ischemic large vessel occlusion stroke. With the widespread application of artificial intelligence technology, especially deep learning algorithms in medical image processing, it is expected to further excavate the DSA images, which can comprehensively evaluate cerebral vascular diseases in multiple phases, angles, and directions.

Prognostic prediction value of quantitative digital subtraction angiography parameters after mechanical thrombectomy in patients with acute ischemic stroke with large vessel occlusion in the anterior circulation of different etiology / 中华神经科杂志

Objective:To explore the prognostic prediction value of quantitative digital subtraction angiography (DSA) parameters in patients with acute anterior circulation ischemic stroke undergoing mechanical thrombectomy, and whether the clinical values vary by stroke etiology.Methods:This study was a post hoc analysis of the Multicenter Prospective Captor Trial. Patients with acute anterior circulation large-vessel occlusion and successful recanalization from April 2018 to July 2019 were screened. Post-processing analysis was performed on the DSA imaging sequence after recanalization, and 4 regions of interest (ROI) were selected in the target vessel: ROI1 (the proximal of the internal carotid artery-C2 segment), ROI2 (the starting point of the internal carotid artery-C7 segment), ROI3 (the end of the middle cerebral artery-M1 segment), and ROI4 (the end of the middle cerebral artery-M2 segment). Time to peak (TTP) was defined as the time at contrast concentration of selected ROI reached its maximum. Relative TTP (rTTP) was calculated by subtracting the TTP of ROI1 from the TTP of distalis ROIs. Successful recanalization was defined as modified Thrombolysis In Cerebral Infarction (mTICI) grade≥2b. Favorable outcomes at 3 months were defined as the modified Rankin Scale score≤2. According to the modified Rankin Scale score, the patients were divided into good prognosis group and poor prognosis group. The differences in clinical characteristics, postoperative hemodynamic parameters, and other data were compared between patients with good and poor prognoses. Univariate and multivariate Logistic regression was used to analyze factors related to a good prognosis. Finally, the prognostic prediction value of hemodynamic parameters was analyzed in patients with different Trial of Org10172 in Acute Stroke Treatment etiological classifications.Results:A total of 245 patients were collected, of which 161 patients [age 69 (60, 76) years, 92 (57.1%) male] were finally included in the analysis, including 36 cases of large artery atherosclerosis (LAA) stroke, 76 cases of cardiogenic embolism (CE), and 49 cases of other causes of stroke. Seventy-one (44.1%) patients had favorable outcomes at 3 months. The post-operative hemodynamic analysis indicated that patients with favorable outcomes ( n=71) had a higher proportion of mTICI grade 3 [54/71 (76.1%) vs 41/90 (45.6%),χ 2=15.26, P<0.001] and lower rTTP 31 [means TTP ROI3-TTP ROI1;0.33 (0.23, 0.54) s vs 0.47 (0.31, 0.65) s, Z=-2.71, P=0.007] than patients with unfavorable outcomes ( n=90). The mTICI score and rTTP 31 were respectively included in multivariate Logistic regression models. It was shown that mTICI grade 3 (adjusted OR=5.97, 95% CI 2.49-14.27, P<0.001) and rTTP 31 (adjusted OR=0.24, 95% CI 0.06-0.99, P=0.048) were significantly associated with favorable outcomes, and the area under the receiver operating characteristic curve of the models had no statistically significant difference ( P=0.170). Subgroup analysis showed that rTTP 31 was significantly associated with the prognosis of patients with LAA stroke ( OR=0, 95% CI 0-0.25, P=0.014), while mTICI grade was associated with the prognosis of patients with CE ( OR=3.91, 95% CI 1.40-10.91, P=0.009) and other etiologies ( OR=7.35, 95% CI 1.92-28.14, P=0.004). Conclusions:In patients with acute anterior circulation ischemic stroke and successful recanalization, both mTICI score and rTTP 31 had significant predictive value for favorable outcomes at 3 months. Moreover, rTTP 31 was significantly associated with the prognosis of patients with LAA stroke, while mTICI score was significantly related to the prognosis of patients with CE and other causes of stroke.

A case of ischemic stroke in a young adult caused by combined defects of protein C and protein S and noncompaction of the ventricular myocardium / 中华神经科杂志

Ischemic stroke in young adults has attracted more and more attention due to the diversity of its etiology. Although atherosclerosis is the most common cause of stroke in young adults, other or unknown causes are not uncommon . To improve clinicians′ understanding of the etiological diagnosis of stroke in young adults, this article reports a case of ischemic stroke in the First Affiliated Hospital of Jinan University. The patient was a 22-year-old male with acute onset who was diagnosed with acute ischemic stroke based on clinical presentation, physical examination, and magnetic resonance imaging of the brain. After actively searching for the cause, laboratory and genetic tests revealed that the patient had inherited thrombophilia (protein C and protein S deficiency), and cardiac magnetic resonance imaging examination found that the patient had noncompaction of the ventricular myocardium.

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.

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.

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.

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.

Synaptic plasticity after ischemic brain injury / 国际脑血管病杂志

Ischemic stroke is a common disease of the nervous system, which is characterized by high incidence, recurrence, disability and mortality rate. The pathological mechanism of ischemic brain injury is complex. Synaptic plasticity injury is considered to be the earliest pathological change after cerebral ischemia, and regulating synaptic plasticity is one of the important mechanisms to promote the recovery of neurological function after stroke. This article reviews the advances in synaptic plasticity after ischemic brain injury, which provides theoretical basis for the development of neuroprotective drugs in the future.

Transcription factor EB attenuates neuronal damage following cerebral ischemia via regulating autophagy-lysosomal pathway / 国际脑血管病杂志

The disorder of autophagy lysosomal pathway (ALP) is an important pathogenesis of neuronal damage after cerebral ischemia, and the restoration of ALP may alleviate neuronal damage after cerebral ischemia. As the main transcription factor regulating ALP, transcription factor EB (TFEB) can directly regulate autophagosome generation, autophagosome-lysosome fusion, and autophagic flux by regulating the expression of autophagic genes and lysosomal genes. Therefore, regulating TFEB can alleviate ALP dysfunction and thereby reduce cerebral ischemic damage. This article reviews the structure, biological function of TFEB and its role in regulating ALP to alleviate neuronal damage after cerebral ischemia.

Endovascular treatment of ischemic moyamoya disease / 国际脑血管病杂志

Moyamoya disease is a relatively rare cerebrovascular disease. Extracranial and intracranial vascular bypass is the first choice for moyamoya disease. However, due to the risk of complications and symptoms recurrence after surgery, there is still some controversy about surgical treatment. In recent years, with the development of minimally invasive interventional technology, the endovascular treatment of atherosclerotic ischemic cerebrovascular disease has been widely carried out in the world. Some doctors are also beginning to try endovascular treatment of ischemic moyamoya disease, but its efficacy and safety are still unclear. This article reviews the endovascular treatment of ischemic moyamoya disease.

Correlation between white matter hyperintensities and outcome after intravenous thrombolysis in patients with acute ischemic stroke / 国际脑血管病杂志

Objective:To investigate the correlation between different degrees of white matter hyperintensities (WMHs) and outcome after intravenous thrombolysis (IVT) in patients with acute ischemic stroke.Methods:Patients with AIS received intravenous thrombolytic therapy with standard dose of alteplase in the First Hospital of Putian City from January 2019 to June 2022 were retrospectively included. The Fazekas scale was used to score the WMHs shown on MRI, and the patients were divided into without or mild WMH group and moderate-to-severe WMH group. The clinical baseline data and the clinical outcome after 3 months of the two groups were compared. The poor outcome was defined as the modified Rankin scale score >2. Multivariate logistic regression analysis was used to determine the influence of the severity of WMHs on the outcome after intravenous thrombolysis. Results:A total of 103 patients with AIS were included. Their age was 64.85±10.89 years old, and 66 (64.1%) were men. There were 60 patients (58.3%) in the without or mild WMH group, and 43 (41.7%) in the moderate-to-severe WMH group. There were significant differences in age, body mass index, systolic blood pressure, baseline National Institutes of Health Stroke Scale (NIHSS) scores, as well as the proportion of patients with hypertension, smoking, hemorrhagic transformation and poor functional outcome at 3 months after onset in different degrees of WMH groups (all P<0.05). There were 73 patients (70.9%) in the good outcome group and 30 (29.1%) in the poor outcome group. There were significant differences in age, body mass index, baseline NIHSS score, WMH score, as well as the proportion of patients with hypertension, large atherosclerotic stroke and symptomatic intracranial hemorrhage between the two groups ( P<0.05). Multivariate logistic regression analysis showed that after adjusting for confounding factors, moderate-to-severe WMHs were the independent risk factors for the poor outcome at 3 months after intravenous thrombolysis (odds ratio 3.810, 95% confidence interval 1.298-1.124; P=0.015). Conclusion:Moderate-to-severe WMHs are associated with the poor outcome in patients with AIS at 3 months after intravenous thrombolysis.

Endovascular recanalization treatment of non-acute symptomatic internal carotid artery occlusion: a single center retrospective case series study / 国际脑血管病杂志

Objective:To investigate the influencing factors, periprocedural complications, and long-term outcomes of successful recanalization after endovascular treatment in patients with non-acute symptomatic internal carotid artery occlusion.Methods:Patients with non-acute internal carotid artery occlusion received endovascular treatment in the Nanjing Stroke Registration System between January 2010 and December 2021 were retrospectively enrolled. Clinical endpoint events were defined as successful vascular recanalization, periprocedural complications (symptomatic embolism and symptomatic intracranial hemorrhage), neurological function improvement, and recurrence of ipsilateral ischemic events. Multivariate logistic regression analysis was used to investigate the independent influencing factors of successful vascular recanalization. Cox proportional hazards regression analysis was used to investigate the correlation between endovascular treatment outcomes and neurological function improvement, as well as ipsilateral ischemic cerebrovascular events. Results:A total of 296 patients were included, of which 190 (64.2%) were successfully recanalized. Multivariate logistic regression analysis showed that symptoms manifest as ischemic stroke (odds ratio [ OR] 3.353, 95% confidence interval [ CI] 1.399-8.038; P=0.007), the time from the most recent symptom onset to endovascular therapy within 1 to 30 d ( OR 2.327, 95% CI 1.271-4.261; P=0.006), proximal conical residual cavity ( OR 2.853, 95% CI 1.242-6.552; P=0.013) and focal occlusion (C1-C2: OR 3.255, 95% CI 1.296-8.027, P=0.012; C6/C7: OR 5.079, 95% CI 1.334-19.334; P=0.017) were the independent influencing factors for successful vascular recanalization. Successful recanalization did not increase the risk of symptomatic intracranial hemorrhage within 7 d after procedure (3.2% vs. 0.9%; P=0.428). The median follow-up time after procedure was 38 months. Cox proportional hazards regression analysis showed that after adjusting for confounding factors, successful recanalization was significantly associated with postprocedural neurological improvement (hazard ratio 1.608, 95% CI 1.091-2.371; P=0.017), and significantly reduced the risk of recurrence of long-term ischemic events (hazard ratio 0.351, 95% CI 0.162-0.773; P=0.010). Conclusion:In patients with non-acute internal carotid artery occlusion, successful endovascular recanalization can effectively reduce the risk of long-term ischemic events without increasing the risk of symptomatic intracranial hemorrhage.

Pathogenesis of cerebral small vessel disease / 国际脑血管病杂志

Cerebral small vessel disease (CSVD) is an important cause of ischemic stroke and vascular dementia, which brings heavy burden to families and society. The prevention and treatment of CSVD has always been a research hotspot, but its pathogenesis is still not completely clear. This article reviews the pathogenesis of CSVD, including chronic cerebral hypoperfusion, blood-brain barrier dysfunction, vascular endothelial dysfunction, interstitial fluid reflux disorder, inflammatory response, and genetic factors, in order to provide more sufficient theoretical basis for early intervention and treatment of CSVD.