Cerebral venous sinus thrombosis presenting as intracerebral hemorrhage and subarachnoid hemorrhage: A case report

@#We present a 66-year-old male presenting with sudden onset of headache. Medical decompression was done and neuroimaging of plain cranial CT angiogram (CTA) and CT venogram (CTV) showed components of subarachnoid hemorrhage, intracerebral hemorrhage and hyperdense appearance of the superior sagittal sinus and proximal left transverse sinus. The following were done to look for etiologic factors: 1. fungal swab to determine the cause of the intracerebral hemorrhage secondary to venous thrombosis as the patient presented with a chronic history of sinusitis, 2. coagulopathy workup to look for a hypercoagulable state, and 3. workup for systemic disease of autoimmune in etiology. Anticoagulation was safely initiated within several days given the regression of the intracerebral hemorrhage along with stable findings of subarachnoid hemorrhage. Here we report cerebral venous sinus thrombosis rarely presenting as acute subarachnoid hemorrhage and intracerebral hemorrhage.

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.

Chirurgie des accidents vasculaires cérébraux hémorragiques au Centre Hospitalier Universitaire Joseph Ravoahangy Andrianavalona, Antananarivo, Madagascar / Surgery of intracerebral haemorrhage at the Joseph Ravoahangy Andrianavalona teaching hospital, Antananarivo, Madagascar

L'accident vasculaire cérébral hémorragique (AVCH) est une interruption de la circulation sanguine par la rupture d'une artère cérébrale qui va provoquer une perte soudaine d'une ou plusieurs fonctions cérébrales. L'objectif de notre étude était de déterminer l'aspect épidemio-clinique et radiologique et de décrire la prise en charge chirurgicale d'un AVCH au Centre Hospitalier Universitaire Joseph Ravoahangy Andrianavalona (CHU JRA), Antananarivo Madagascar. Méthodes : Il s'agit d'une étude rétrospective et descriptive de 125 cas d'AVCH opérés sur des patients hospitalisés du Janvier 2017 au 31 Décembre 2019. Résultats : Nous avons noté une prédominance masculine de 55% avec un Sex ratio de 0,82 ; dont l'âge moyen était de 52,8 ans. Le facteur de risque le plus rencontré était l'hypertension artérielle (HTA) avec 58,4% des cas. Les motifs d'admission étaient les troubles de la conscience (63,2%) et les déficits moteurs (44,8%). Les signes à l'examen étaient surtout l'hémiplégie (55,2%), la dysarthrie (22,4%). Les hématomes étaient lobaires dans 80,8% des cas et 19,2% au niveau de la fosse postérieure. La technique chirurgicale la plus utilisée était l'évacuation de l'hématome par craniotomie. Les séquelles étaient dominées par l'hémiparésie et l'aphasie respectivement 53.6% et 10.4%. Le taux de mortalité a été de 8%. Conclusion : La chirurgie tient une place primordiale dans la prise en charge des AVCH au CHU JRA.

Troubles de la conscience au service de réanimation polyvalente du Centre Hospitalier Universitaire Analakininina, Toamasina, Madagascar / Impaired consciousness in the intensive care unit at Analankininina Teaching Hospital of Toamasina, Madagascar

La survenue d'un coma ou de troubles de la conscience en réanimation est très fréquemment observée et leur présence est associée à un pronostic sévère. Nos objectifs étaient de décrire le profil épidémio-clinique des patients admis pour coma et trouble de la conscience ainsi que les principales étiologies de ces manifestations cliniques. Méthodes : Il s'agissait d'une étude prospective, descriptive, longitudinale de Juin à Novembre 2019. Le cadre de notre étude était le service de réanimation polyvalente du centre hospitalier universitaire (CHU) Analakininina Toamasina. Résultats : Nous avions recensé 77 patients dont 37 femmes et 40 hommes (sex ratio de 1,081). La moyenne d'âge était de 39 +/-17 ans. La majorité des patients soit 67% présentait un trouble de la conscience, le reste (31%) était comateux. La principale étiologie des troubles rencontrés était l'AVC (53%) dont 61% était hémorragiques, 17% ischémiques, et 22% non étiquetés. Plus de la moitié des patients avaient évolué vers le décès (61%). Conclusion : Pour l'amélioration du pronostic des patients, il serait nécessaire de connaitre les étiologies fréquentes afin d'adapter la prise en charge

Circular RNA hsa_circ_0087893 participates in intraventricular hemorrhage occurrence and progression possibly as a competitive endogenous RNA in preterm infants / 南方医科大学学报

OBJECTIVE@#To screen for differentially expressed circular RNAs (circRNAs) in the serum of preterm infants with intraventricular hemorrhage (IVH) and explore the competitive endogenous RNA (ceRNA) mechanism of circRNAs in IVH in these infants.@*METHODS@#Fifty preterm infants (gestational age of 28 to 34 weeks) admitted in our department between January, 2019 and January, 2020 were enrolled in this study, including 25 with a MRI diagnosis of IVH and 25 without IVH. Serum samples were collected from 3 randomly selected infants from each group for profiling differentially expressed circRNAs using circRNA array technique. Gene ontology (GO) and pathway analyses were performed to reveal the function of the identified circRNAs. The circRNA-miRNA-mRNA network was constructed to identify the co-expression network of hsa_circ_ 0087893.@*RESULTS@#A total of 121 differentially expressed circRNAs were identified in the infants with IVH, including 62 up-regulated and 59 down-regulated circRNAs. GO and pathway analyses showed that these circRNAs were involved in multiple biological processes and pathways, including cell proliferation, activation and death, DNA damage and repair, retinol metabolism, sphingolipid metabolism, cell adhesion molecules. Among these circRNAs, hsa_circ_0087893 was found to have significant down-regulation in IVH group and co-express with 41 miRNAs and 15 mRNAs (such as miR-214-3p, miR-761, miR-183-5p, AKR1B1, KRT34, PPP2CB, and HPRT1).@*CONCLUSION@#The circRNA hsa_circ_0087893 may function as a ceRNA and play an important role in the occurrence and progression of IVH in preterm infants.

Efficacy of electroacupuncture on acute intracerebral hemorrhage and its effect on serum AQP4 in patients / 中国针灸

OBJECTIVE@#To observe the effects on neural function, living ability and mental state of the patients with acute intracerebral hemorrhage (ICH), as well as aquaporin 4 (AQP4) in the serum after treated with electroacupuncture (EA) on the base of routine therapy of western medicine.@*METHODS@#Seventy-two acute ICH patients were randomized into an observation group (36 cases, 4 cases dropped off) and a control group (36 cases, 2 cases dropped off). In the control group, the conventional treatment was delivered such as stopping bleeding, preventing re-hemorrhage, controlling blood pressure, mitigating neural edema and reducing intracranial pressure. In the observation group, on the base of the treatment in the control group, EA was supplemented. Acupoints included Shuigou (GV 26), bilateral Neiguan (PC 6) and Sanyinjiao (SP 6) etc. Electric stimulation was operated at Neiguan (PC 6) and Sanyinjiao (SP 6) on the same side, with disperse-dense wave, and 2 Hz/100 Hz in frequency, tolerable current intensity. Electric stimulation was delivered for 30 min in each treatment, once daily and for 6 times per week. The duration of treatment was 2 weeks in the two groups. Before and after treatment, changes of the scores of National Institutes of Health stroke scale (NIHSS), modified Barthel index (MBI) and mini-mental state examination (MMSE), as well as AQP4 content in the serum were observed in the two groups; the efficacy and safety were compared between the two groups.@*RESULTS@#The NIHSS scores and the serum AQP4 content decreased after treatment when compared with those before treatment in the two groups (P<0.05), while, MBI and MMSE scores increased (P<0.05). In the observation group, NIHSS score and serum AQP4 content were lower than those of the control group (P<0.05), and MBI and MMSE scores were higher (P<0.05). The total effective rate of the observation group was 93.8% (30/32), higher than that of the control group (73.5%, 25/34, P<0.05). The treatment in the two groups was safe, without adverse reactions and events occurring in the patients.@*CONCLUSION@#Electroacupuncture, on the base of conventional treatment of western medicine, can effectively improve the neural function, living ability, mental state and serum AQP4 content of the patients with acute ICH. It is suggested that the effective treatment by electroacupuncture may be related to the regulation of the serum AQP4 content.

Association between gut microbiome and intracerebral hemorrhage based on genome-wide association study data / 中南大学学报(医学版)

OBJECTIVES@#Intracerebral hemorrhage (ICH) has the highest mortality and disability rates among various subtypes of stroke. Previous studies have shown that the gut microbiome (GM) is closely related to the risk factors and pathological basis of ICH. This study aims to explore the causal effect of GM on ICH and the potential mechanisms.@*METHODS@#Genome wide association study (GWAS) data on GM and ICH were obtained from Microbiome Genome and International Stroke Genetics Consortium. Based on the GWAS data, we first performed Mendelian randomization (MR) analysis to evaluate the causal association between GM and ICH. Then, a conditional false discovery rate (cFDR) method was conducted to identify the pleiotropic variants.@*RESULTS@#MR analysis showed that Pasteurellales, Pasteurellaceae, and Haemophilus were negatively correlated with the risk of ICH, whileVerrucomicrobiae, Verrucomicrobiales, Verrucomicrobiaceae, Akkermansia, Holdemanella, and LachnospiraceaeUCG010 were positively correlated with ICH. By applying the cFDR method, 3 pleiotropic loci (rs331083, rs4315115, and rs12553325) were found to be associated with both GM and ICH.@*CONCLUSIONS@#There is a causal association and pleiotropic variants between GM and ICH.

Risk factors and prognosis of hypotension within 72 hours after birth in extremely preterm infants / 中国当代儿科杂志

OBJECTIVES@#To investigate the risk factors and prognosis of hypotension within 72 hours after birth in extremely preterm infants.@*METHODS@#A retrospective analysis was conducted on clinical data of extremely preterm infants admitted to the Children's Hospital of Zhejiang University School of Medicine from January 2019 to April 2022. Based on the presence of hypotension within 72 hours after birth, the eligible infants were divided into a hypotension group (41 cases) and a normotension group (82 cases). The clinical characteristics, echocardiographic parameters within 72 hours after birth, and early complications were compared between the two groups. Multivariate logistic regression analysis was used to explore the risk factors for hypotension within 72 hours after birth, and receiver operating characteristic curve analysis was performed to evaluate the predictive value of relevant indicators for the occurrence of hypotension within 72 hours after birth in the preterm infants.@*RESULTS@#The proportion of infants who required medication or surgical closure of patent ductus arteriosus (PDA), the proportions of infants with intraventricular hemorrhage ≥ grade III and severe pulmonary hemorrhage, and the mortality rate within 7 days in the hypotension group were significantly higher than those in the normotension group (P<0.05). Multivariate logistic regression analysis showed that lower birth weight, larger PDA diameter, and hemodynamically significant PDA were risk factors for the occurrence of hypotension within 72 hours after birth in extremely preterm infants (P<0.05). The receiver operating characteristic curve analysis showed that the combination of birth weight, PDA diameter, and hemodynamically significant PDA had an area under the curve of 0.873 (95%CI: 0.802-0.944, P<0.05) for predicting hypotension within 72 hours after birth, with a sensitivity of 73.2% and specificity of 91.5%.@*CONCLUSIONS@#Hypotension within 72 hours after birth is closely related to birth weight and PDA, and increases the risk of early severe complications and mortality in extremely preterm infants.

Mechanism of Zhongfeng Xingnao Decoction in improving microcirculatory disorders in cerebral hemorrhage based on network pharmacology and molecular docking techniques / 中国中药杂志

This study aimed to explore the mechanism of Zhongfeng Xingnao Decoction(ZFXN) in intervening microcirculatory di-sorders in cerebral hemorrhage by network pharmacology and molecular docking techniques. The information on the components of ZFXN was obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database, and the predicted targets of chemical components were obtained from PubChem and SwissTargetPrediction. The relevant targets of cerebral hemorrhage and microcirculatory disorders were collected from the GeneCards database, and the common targets of the components and diseases were analyzed by the Database for Annotation, Visualization, and Integrated Discovery(DAVID) for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses. Visualization of the correlation network was carried out using Cytoscape software to further screen important chemical components for molecular docking prediction with disease targets. The animal experiment validation was performed using modified neurological severity score(mNSS), enzyme-linked immunosorbent assay(ELISA), quantitative real-time polymerase chain reaction(qRT-PCR), immunofluorescence, and Western blot to detect the effects of ZFXN intervention in mice with cerebral hemorrhage. The results showed that there were 31 chemical components and 856 targets in the four drugs contained in ZFXN, 173 targets for microcirculatory disorders in cerebral hemorrhage, and 57 common targets for diseases and components. The enrichment analysis showed that common targets were mainly involved in biological processes, such as cell proliferation and apoptosis, and signaling pathways, such as tumor pathway, viral infection, phosphoinositide-3-kinase/protein kinase B(PI3K/AKT) signaling pathway, and mitogen-activated protein kinase(MAPK) signaling pathway. Molecular docking results revealed that the common components β-sitosterol of Rhei Radix et Rhizoma, Notoginseng Radix et Rhizoma, and Ginseng Radix et Rhizoma Rubra showed good docking with proto-oncogene tyrosine-protein kinase(SRC), signal transducer and activator of transcription 3(STAT3), phosphoinositide-3-kinase catalytic alpha polypeptide gene(PIK3CA), recombinant protein tyrosine phosphatase non receptor type 11(PTPN11), AKT1, epidermal growth factor receptor(EGFR), calcium adhesion-associated protein beta 1(CTNNB1), vascular endothelial growth factor A(VEGFA), and tumor protein p53(TP53). Moreover, sennoside E of Rhei Radix et Rhizoma showed good docking with MAPK1. The results revealed that the ZFXN relieved the neural injury in mice with cerebral hemorrhage, decreased the expression of S100 calcium-binding protein B(S100β), neuron specific enolase(NSE), matrix metalloproteinase 9(MMP9), tumor necrosis factor α(TNF-α), interleukin 1β(IL-1β), SRC, EGFR, CTNNB1, VEGFA, TP53, glial fibrillary acidic protein(GFAP), and leukocyte differentiation antigen 86(CD86), and increased the expression of p-PI3K, p-AKT, and zona occludens 1(ZO-1). The results indicate that ZFXN may inhibit neuronal apoptosis and inflammatory response through PI3K/AKT/p53 pathway to protect the blood-brain barrier, thereby slowing down microcirculatory impairment in cerebral hemorrhage.

Clinical analysis of 15 pregnant women complicated with moyamoya disease / 中华妇产科杂志

Objective: To explore the effects of pregnancy complicated with moyamoya disease on maternal and fetal outcomes. Methods: The general clinical data and maternal and fetal outcomes of 20 pregnancies of 15 patients with moyamoya disease admitted to the First Affiliated Hospital of Zhengzhou University from January 2012 to October 2022 were retrospectively analyzed. Results: (1) General information: among the 20 pregnancies of 15 clearly diagnosed pregnant women complicated with moyamoya disease, 12 were diagnosed before pregnancy (60%, 12/20), 3 were diagnosed during pregnancy (15%, 3/20), and 5 were diagnosed during puerperal period (25%, 5/20). There were 7 cases of primipara (35%, 7/20) and 13 cases of multipara (65%, 13/20). (2) Pregnancy complications and maternal and infant outcomes: among the 20 pregnancies of 15 pregnant women with moyamoya disease, there were 9 pregnancy complications (45%, 9/20), including 5 gestational hypertension (25%, 5/20), 2 severe pre-eclampsia (10%, 2/20), 1 hyperlipidemia and 1 gestational diabetes mellitus (5%, 1/20). There were 2 case of drug abortion in the first trimester, 3 cases of labor induction in the second trimester, and 15 cases of delivery during the third trimester. All the 15 deliveries were cesarean section, of which 11 (11/15) were cesarean sections with medical indications, and 4 (4/15) were cesarean sections caused by personal factors. General anesthesia was used in 5 cases (5/15), epidural block anesthesia in 7 cases (7/15), and combined spinal and epidural anesthesia in 3 cases (3/15). The median gestational age of 15 neonates was 37.2 weeks (34.0 to 40.8 weeks), with 10 cases (10/15) were full-term infants, and 5 (5/15) were preterm infants (3 of which were associated with hypertensive disorder complicating pregnancy). The birth weight of 15 neonates was (2 853±454) g. Four neonates were admitted to neonatal intensive care unit (NICU), of which 3 cases were admitted to NICU due to premature delivery and 1 case was admitted to NICU due to neonatal jaundice. There was no neonatal asphyxia or death. All neonates were followed up from 4 months to 6 years after birth, and all grew well. (3) Neurological symptoms during pregnancy: 8 cases (40%, 8/20) had neurological symptoms during pregnancy, and 6 cases (30%, 6/20) had hemorrhagic symptoms, of which 3 cases occurred during the puerperal period (3/6). There were 2 cases of ischemic symptoms (10%, 2/20), all of which occurred during the puerperal period (2/2). (4) Analysis of factors related to the occurrence of cerebral hemorrhage: the incidence of cerebral hemorrhage in patients with moyamoya disease diagnosed before pregnancy was significantly lower than that in those without a clear diagnosis, and the incidence of cerebral hemorrhage in women with moyamoya disease was lower than that in primipara (all P<0.01). The incidence of cerebral hemorrhage in moyamoya patients without hypertensive disorder complicating pregrancy was lower than that in patients with hypertensive disorder complicating pregrancy, but the difference was not statistically significant (P>0.05). Conclusions: Pregnancy combined with moyamoya disease has adverse effects on maternal and infant outcomes, and the incidence of pregnancy complications increases. Cerebral hemorrhage occurres in prenatal and puperium, while cerebral ischemia occurres mainly in puperium.

Potential drug-drug interactions among patients with spontaneous intracerebral hemorrhage treated at the Neurological Intensive Care Unit: a single-center experience

Abstract Our aim was to determine the prevalence of potential drug-drug interactions (pDDIs) and to identify relevant factors associated with the occurrence of the most dangerous or contraindicated pDDIs (pCDDIs) in hospitalized patients with spontaneous intracerebral hemorrhage (sICH). A retrospective cross-sectional study was performed enrolling all consecutive patients with sICH treated at the Neurological Intensive Care Unit, Clinical Center in Kragujevac, Serbia, during the three-year period (2012-2014). The inclusion criteria encompassed patients aged 18 years and over, those diagnosed with ICH, and those prescribed at least two drugs during hospitalization, while we did not include patients whose hospitalization lasted less than 7 days, those who were diagnosed with other neurological diseases and patients with incomplete medical files. For each day of hospitalization, the online checker Micromedex® software was used to identify pDDIs and classify them according to severity. A total of 110 participants were analysed. A high prevalence of pDDIs (98.2%) was observed. The median number of pDDIs regardless of severity, was 8.00 (IQR 4.75-13.00;1-30). The pairs of drugs involving cardiovascular medicines were the most commonly identified pDDIs. Twenty percent of the total number of participants was exposed to pCDDIs. The use of multiple drugs from different pharmacological-chemical subgroups and the prescribing of anticoagulant therapy significantly increase the chance of pCDDI (aOR with 95% CI 1.19 (1.05-1.35) and 7.40 (1.13-48.96), respectively). This study indicates a high prevalence of pDDIs and pCDDIs in patients with sICH. The use of anticoagulant therapy appears to be the only modifiable clinically relevant predictor of pCDDIs.

Neuroimagen en pacientes con infección por COVID-19 descripción de hallazgos y revisión de la literatura / Neuroimaging in patients with COVID-19: findings description and review of the literature

El síndrome respiratorio agudo severo causado por coronavirus 2 (SARS-CoV-2) es responsable de la propagación mundial de la enfermedad por coronavirus (COVID-19). Nuestro conocimiento hasta el momento del impacto de este virus en el sistema nervioso es limitado. El propósito de este artículo es revisar el espectro de los diversos hallazgos en neuroimágenes asi como la fisiopatología en los pacientes con COVID-19. Se necesitan estudios futuros que examinen el impacto de los síntomas y su correlación con las neuroimágenes durante el curso de la enfermedad, para aclarar y evaluar aún más el vínculo entre las complicaciones neurológicas y el resultado clínico, así como limitar las consecuencias a largo plazo.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the global spread of coronavirus disease (COVID-19). Our understanding, so far, of the impact this virus has on the nervous system is limited. Our article aims to review the spectrum of neuroimaging findings in patients with COVID 19, as well as, their underlying pathophysiology. Future studies examining the impact of symptoms and their correlation with neuroimaging findings duirng the course of the disease are needed to further clarify and evaluate the association between neurological complications and clinical outcome, as well as to limit long-term consequences.

Suppression of HMGB1 inhibits neuronal autophagy and apoptosis to improve neurological deficits in rats following intracerebral hemorrhage / 南方医科大学学报

OBJECTIVE@#To investigate the effect of suppressing high-mobility group box 1 (HMGB1) on neuronal autophagy and apoptosis in rats after intracerebral hemorrhage (ICH) in rats.@*METHODS@#Rat models of ICH induced by intracerebral striatum injection of 0.2 U/mL collagenase Ⅳ were treated with 1 mg/kg anti-HMGB1 mAb or a control anti-IgG mAb injected via the tail immediately and at 6 h after the operation (n=5). The rats in the sham-operated group (with intracranial injection of 2 μL normal saline) and ICH model group (n=5) were treated with PBS in the same manner after the operation. The neurological deficits of the rats were evaluated using modified neurological severity score (mNSS). TUNEL staining was used to detect apoptosis of the striatal neurons, and the expressions of HMGB1, autophagy-related proteins (Beclin-1, LC3-Ⅱ and LC3-Ⅰ) and apoptosis-related proteins (Bcl-2, Bax and cleaved caspase-3) in the brain tissues surrounding the hematoma were detected using Western blotting. The expression of HMGB1 in the striatum was detected by immunohistochemistry, and serum level of HMGB1 was detected with ELISA.@*RESULTS@#The rat models of ICH showed significantly increased mNSS (P < 0.05), which was markedly lowered after treatment with anti- HMGB1 mAb (P < 0.05). ICH caused a significant increase of apoptosis of the striatal neurons (P < 0.05), enhanced the expressions of beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 (P < 0.05), lowered the expressions of LC3-Ⅰ and Bcl-2 (P < 0.05), and increased the content of HMGB1 (P < 0.05). Treatment with anti-HMGB1 mAb obviously lowered the apoptosis rate of the striatal neurons (P < 0.05), decreased the expressions of Beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 (P < 0.05), increased the expressions of LC3-Ⅰ and Bcl-2 (P < 0.05), and reduced the content of HMGB1 in ICH rats (P < 0.05).@*CONCLUSION@#Down- regulation of HMGB1 by anti-HMGB1 improves neurological functions of rats after ICH possibly by inhibiting autophagy and apoptosis of the neurons.

Effects of butyphthalide on microglia polarization after intracerebral hemorrhage and the underlying mechanisms / 中南大学学报(医学版)

OBJECTIVES@#Because intracerebral hemorrhage (ICH) has high morbidity, disability and mortality, it is significant to find new and effective treatments for ICH. This study aims to explore the effect of butyphthalide (NBP) on neuroinflammation secondary to ICH and microglia polarization.@*METHODS@#A total of 48 healthy male SD rats were randomly divided into 6 groups: a sham 24 h group, a sham 72 h group, an ICH 24 h group, an ICH 72 h group, an ICH+NBP 24 h group, and an ICH+NBP 72 h group (8 rats per group). After operation, the neurological deficiencies were assessed based on improved Garcia scores and corner test. The expressions of Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), aquaporin-4 (AQP4), zonula occludens-1 (ZO-1), occludin, CD68, CD86, and CD206 were observed by Western blotting. Inflammatory cytokines were detected by ELISA. The immunofluorescence was to detect the polarization of microglia.@*RESULTS@#1) Compared with the sham groups, the expression of TLR4 (24 h: P<0.05; 72 h: P<0.01), NF-κB (both P<0.01) and Nrf2 (both P<0.01) in the perihematoma of the ICH group was increased, leading to microglia activation (P<0.01). The expressions of IL-6 (24 h: P<0.05; 72 h: P<0.01) and TNF-α (both P<0.01), the pro-inflammatory cytokines were up-regulated, and the expression of anti-inflammatory cytokine IL-4 was down-regulated (both P<0.01). Besides, the expression of AQP4 was enhanced (both P<0.01). The protein level of tightly connected proteins (including ZO-1, occludin) was decreased (all P<0.01). The neurological function of the rats in the ICH group was impaired in the 2 time points (both P<0.01). 2) Compared with the sham group at 24 h and 72 h after the intervention of NBP, the expressions of TLR4 (both P<0.05) and NF-κB (both P<0.01) were significantly declined, and the expression of Nrf2 was further enhanced (both P<0.05) in the perihematoma of the ICH+NBP group. Furthermore, the expression of M1 microglia marker was inhibited (P<0.05), and the polarization of microglia to the M2 phenotype was promoted (P<0.01). 3) In terms of inflammation after ICH, the IL-4 expression in the ICH+NBP group was increased compared with the ICH group (24 h: P<0.05; 72 h: P<0.01); the expression of IL-6 was decreased significantly in the ICH+NBP 72 h group (P<0.01); the level of AQP4 was declined significantly in the ICH+NBP 24 h group (P<0.05), there was a downward trend in the 72-hour intervention group but without significant statistical difference. 4) Compared with the ICH group, the ZO-1 protein levels were increased (24 h: P<0.05; 72 h: P<0.01), and the symptoms of nerve defect were improved eventually (both P<0.05) in the ICH+NBP groups.@*CONCLUSIONS@#After ICH, the TLR4/NF-κB pathway is activated. The M1 microglia is up-regulated along with the release of detrimental cytokines, while the anti-inflammatory cytokines are down-regulated. The expression of AQP4 is increased, the tight junction proteins from the blood-brain barrier (BBB) is damaged, and the neurological function of rats is impaired. On the contrary, NBP may regulate microglia polarization to M2 phenotype and play a role in the neuroprotective effect mediated via inhibiting TLR4/NF-κB and enhancing Nrf2 pathways, which relieves the neuroinflammation, inhibits the expression of AQP4, repairs BBB, and improves neurological functional defects.

Performance of low-dose CT image reconstruction for detecting intracerebral hemorrhage: selection of dose, algorithms and their combinations / 南方医科大学学报

OBJECTIVE@#To investigate the performance of different low-dose CT image reconstruction algorithms for detecting intracerebral hemorrhage.@*METHODS@#Low-dose CT imaging simulation was performed on CT images of intracerebral hemorrhage at 30%, 25% and 20% of normal dose level (defined as 100% dose). Seven algorithms were tested to reconstruct low-dose CT images for noise suppression, including filtered back projection algorithm (FBP), penalized weighted least squares-total variation (PWLS-TV), non-local mean filter (NLM), block matching 3D (BM3D), residual encoding-decoding convolutional neural network (REDCNN), the FBP convolutional neural network (FBPConvNet) and image restoration iterative residual convolutional network (IRLNet). A deep learning-based model (CNN-LSTM) was used to detect intracerebral hemorrhage on normal dose CT images and low-dose CT images reconstructed using the 7 algorithms. The performance of different reconstruction algorithms for detecting intracerebral hemorrhage was evaluated by comparing the results between normal dose CT images and low-dose CT images.@*RESULTS@#At different dose levels, the low-dose CT images reconstructed by FBP had accuracies of detecting intracerebral hemorrhage of 82.21%, 74.61% and 65.55% at 30%, 25% and 20% dose levels, respectively. At the same dose level (30% dose), the images reconstructed by FBP, PWLS-TV, NLM, BM3D, REDCNN, FBPConvNet and IRLNet algorithms had accuracies for detecting intracerebral hemorrhage of 82.21%, 86.80%, 89.37%, 81.43%, 90.05%, 90.72% and 93.51%, respectively. The images reconstructed by IRLNet at 30%, 25% and 20% dose levels had accuracies for detecting intracerebral hemorrhage of 93.51%, 93.51% and 93.06%, respectively.@*CONCLUSION@#The performance of reconstructed low-dose CT images for detecting intracerebral hemorrhage is significantly affected by both dose and reconstruction algorithms. In clinical practice, choosing appropriate dose level and reconstruction algorithm can greatly reduce the radiation dose and ensure the detection performance of CT imaging for intracerebral hemorrhage.

Influence of umbilical cord milking versus delayed cord clamping on the early prognosis of preterm infants with a gestational age of <34 weeks: a Meta analysis / 中国当代儿科杂志

OBJECTIVES@#To study the influence of umbilical cord milking versus delayed cord clamping on the early prognosis of preterm infants with a gestational age of <34 weeks.@*METHODS@#PubMed, Web of Science, Embase, the Cochrane Library, CINAHL, China National Knowledge Infrastructure, Wanfang Data, Weipu Database, and SinoMed were searched for randomized controlled trials on umbilical cord milking versus delayed cord clamping in preterm infants with a gestational age of <34 weeks published up to November 2021. According to the inclusion and exclusion criteria, two researchers independently performed literature screening, quality evaluation, and data extraction. Review Manger 5.4 was used for Meta analysis.@*RESULTS@#A total of 11 articles were included in the analysis, with 1 621 preterm infants in total, among whom there were 809 infants in the umbilical cord milking group and 812 in the delayed cord clamping group. The Meta analysis showed that compared with delayed cord clamping, umbilical cord milking increased the mean blood pressure after birth (weighted mean difference=3.61, 95%CI: 0.73-6.50, P=0.01), but it also increased the incidence rate of severe intraventricular hemorrhage (RR=1.83, 95%CI: 1.08-3.09, P=0.02). There were no significant differences between the two groups in hemoglobin, hematocrit, blood transfusion rate, proportion of infants undergoing phototherapy, bilirubin peak, and incidence rates of complications such as periventricular leukomalacia and necrotizing enterocolitis (P>0.05).@*CONCLUSIONS@#Compared with delayed cord clamping, umbilical cord milking may increase the risk of severe intraventricular hemorrhage in preterm infants with a gestational age of <34 weeks; however, more high-quality large-sample randomized controlled trials are needed for further confirmation.

Effects of MCC950 on nerve injury in rats with intracerebral hemorrhage / 中国应用生理学杂志

Objective: To investigate the effects of the pyrin domain-containing protein 3 (NLRP3) inflammasome inhibitor MCC950 on nerve injury in rats with intracerebral hemorrhage(ICH). Methods: Seventy-two SD rats were randomly divided into three groups (n=24): Sham group, ICH group and MCC950 group. ICH group and MCC950 group rats were injected with autogenous non-anticoagulant blood to establish ICH model, and then the rats in MCC950 group were intraperitoneally injected with MCC950 at the dose of 10 mg/kg(2 mg/ml) for 3 days after ICH model was established. Seventy-two hours after the establishment of the model, the forelimb placement test, the corner test and mNSS score were performed to observe the neurological function of the rats with ICH. The volume of hematoma was observed in fresh brain tissue sections. HE staining was used to observe the pathological changes of brain tissue. The dry-wet weight ratio was calculated to evaluate the changes of brain tissue edema. The degeneration of neurons was observed by FJC staining. The neuronal apoptosis was observed by TUNEL staining. The protein expression and activation levels of NLRP3, ASC, caspase-1, IL-1β, IL-18 and GSDMD were determined by Western blot. Results: Compared with sham group, the percentage of successful placement of left forelimb and left turn was decreased significantly (P＜0.01, P＜0.05), mNSS score was increased significantly (P＜0.01) in ICH group. Hematoma volume was increased significantly, the number of microglial cells around the hematoma was increased, the number of neurons was decreased, nerve cell swelled, some cells showed pyknotic necrosis, and the staining was deepened. The water content of the right base was increased significantly (P＜0.05). The number of FJC positive and TUNEL positive cells around the hematoma was increased significantly (P＜0.05). The levels of NLRP3, ASC, caspase-1, pro-caspase-1, caspase-1/pro-caspase-1 ratio, GSDMD-N, GSDMD, GSDMD-N/GSDMD ratio, IL-1β and IL-18 were increased significantly (P＜0.01, P＜ 0.05). Compared with ICH group, the percentage of successful placement of left forelimb and left turn was increased significantly in MCC950 group (P＜0.05), while the mNSS score and the volume of hematoma were decreased significantly (P＜0.01), the swelling degree of nerve cells around the hematoma was reduced significantly, and the number of pyrotic necrotic cells was decreased. The water content of the right base was decreased significantly (P＜0.05), and the number of FJC positive and TUNEL positive cells around the hematoma was decreased significantly (P＜0.05). The levels of NLRP3, ASC, caspase-1, pro-caspase-1, caspase-1/pro-caspase-1 ratio, GSDMD-N, GSDMD, GSDMD-N/GSDMD ratio, IL-1β and IL-18 were decreased significantly (P＜0.05). Conclusion: MCC950 can ameliorate nerve injury after ICH by inhibiting NLRP3 inflammasome mediated inflammation and pyroptosis.

Ulinastatin alleviates early brain injury after intracerebral hemorrhage by inhibiting oxidative stress and neuroinflammation via ROS/MAPK/Nrf2 signaling pathway

Purpose: Spontaneous intracerebral hemorrhage (ICH) is still a major public health problem, with high mortality and disability. Ulinastatin (UTI) was purified from human urine and has been reported to be anti-inflammatory, organ protective, and antioxidative stress. However, the neuroprotection of UTI in ICH has not been confirmed, and the potential mechanism is unclear. In the present study, we aimed to investigate the neuroprotection and potential molecular mechanisms of UTI in ICH-induced early brain injury in a C57BL/6 mouse model. Methods: The neurological score, brain water content, neuroinflammatory cytokine levels, oxidative stress levels, and neuronal damage were evaluated. Results: UTI treatment markedly increased the neurological score, alleviated brain edema, decreased the levels of the inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, and NF-κB, decreased the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and upregulated the levels of glutathione (GSH), superoxide dismutase (SOD), and Nrf2. This finding indicated that UTI-mediated inhibition of neuroinflammation and oxidative stress alleviated neuronal damage after ICH. The neuroprotective capacity of UTI is partly dependent on the ROS/MAPK/Nrf2 signaling pathway. Conclusions: UTI improves neurological outcomes in mice and reduces neuronal death by protecting against neural neuroinflammation and oxidative stress.

Vasoconstricción cerebral fatal, presentación inusual de una enfermedad inusual / Fatal reversible cerebral vasoconstriction syndrome: An unusual presentation of a rare disease

Resumen | El síndrome de vasoconstricción cerebral reversible se produce por la constricción variable, segmentaria y multifocal, de las arterias cerebrales y, generalmente, es de curso benigno. Se describe el caso de una mujer de 49 años que consultó por cefalea, síntomas visuales y convulsiones; tres días después, presentaba áreas de vasoconstricción en, por lo menos, dos territorios vasculares y dos segmentos de las mismas arterias. Fue internada en la unidad de cuidados intensivos para controlarle la presión arterial y recibir tratamiento médico. Tuvo una evolución tórpida y, en el séptimo día de hospitalización, desarrolló edema cerebral maligno, tras lo cual ocurrió la muerte cerebral. Se inició entonces el plan de donación de órganos y, posteriormente, se practicó una autopsia guiada del cerebro. El estudio de patología descartó vasculitis y reveló áreas de hemorragia en la convexidad cerebral. Se discuten los aspectos más relevantes de los casos con evolución fulminante informados en la literatura científica. El síndrome de vasoconstricción cerebral reversible se asocia con resultados fatales cuando los pacientes tienen una deficiencia neurológica focal, la neuroimagen inicial muestra alteraciones y hay un deterioro clínico rápido. Es importante conocer los factores asociados con un mal pronóstico, y establecer estrategias tempranas de intervención y prevención.

Abstract | The reversible cerebral vasoconstriction syndrome is a variable, segmental, and multifocal constriction of brain arteries, usually with a benign course. We describe the case of a 49-year-old woman who presented with headaches, visual symptoms, and seizures. Three days after admission, vasoconstriction areas were found in at least two vascular territories in two segments of the same arteries. The patient was admitted to the intensive care unit where her blood pressure was monitored and she received medical treatment. Surprisingly, the patient presented an unpredicted evolution in developing malignant cerebral edema on the seventh day after admission. She then suffered brain death and was taken to organ donation. A guided nervous system necropsy was later performed. The pathology discarded vasculitis and exhibited hemorrhage areas in the cerebral convexity. Herein, we discuss the most relevant aspects of cases with fulminant evolution reported in the literature. The reversible cerebral vasoconstriction syndrome is usually associated with fatal outcomes when patients exhibit focalization, their first neuroimaging typically shows disturbances, and a rapid clinical deterioration occurs. It is crucial to identify factors linked to poor prognosis and set intervention strategies and early prevention.

Impact of bundle implementation on the incidence of peri/intraventricular hemorrhage among preterm infants: a pre-post interventional study

ABSTRACT BACKGROUND: Peri/intraventricular hemorrhage (PIVH) is a frequent cause of death and morbidity among preterm infants. Few studies have addressed the use of bundles for preventing PIVH. OBJECTIVE: To evaluate the efficacy of a bundle of interventions designed to decrease the incidence of intraventricular hemorrhage at hospital discharge among preterm infants. DESIGN AND SETTING: Pre-post interventional study with retrospective and prospective data collection performed before and after bundle implementation in the neonatal intensive care unit of a university hospital. METHODS: Infants with gestational age < 32 weeks without malformations, who survived > 6 days were included. The bundle consisted of the following actions during the first 72 hours of life: maintenance of head in neutral position with the body in supine position, minimal handling, including delay of lumbar puncture until after 72 hours and absence of respiratory therapy maneuvers. Cranial ultrasound was performed on days 3, 7 and 28, or later if needed. The effect of the bundle was analyzed through logistic regression and results were adjusted for confounding variables. RESULTS: 167 infants met the inclusion criteria; 146 (87%) were analyzed. Bundle implementation was associated with decreased chances of PIVH at hospital discharge (odds ratio 0.29; 95% confidence interval 0.13-0.65). Cerebrospinal fluid collection within the first 72 hours increased the odds of PIVH of any grade during the hospital stay fourfold, after adjustment for all variables included in the model. CONCLUSION: Implementation of a bundle of interventions to avoid intraventricular hemorrhage was effective for decreasing the incidence of all grades of PIVH in preterm infants.