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Background: Opium use disorder is a significant health problem in our country, leading to a considerable number of health issues. Opium has several detrimental effects on its consumers. However, the effect of Opium use disorder on intracerebral hemorrhage (ICH) has not been evaluated. This study aims to evaluate the relationship between Opium use disorder and ICH. Methods: In this case-control study, 402 patients with ICH and 404 patients without ICH enrolled. Opium use disorder, other vascular risk factors including diabetes mellitus, hypertension, hyperlipidemia, and tobacco smoking was compared between these groups. Patients with ICH were divided into two groups; first group are patients with history of Opioid Use Disorder and second group are those patients without Opioid Use Disorder. ICH features including clinical and imaging characteristics and prognostic findings were compared between patients with and without Opium use disorder. Results: This case-control study of 806 participants found that hypertension (OR = 6.84, 95% CI: 5.03-9.34, p-value: <0.001), Opium use disorder (OR = 4.23, 95% CI: 2.42-7.35, p-value: <0.001) and tobacco smoking (OR = 1.47, 95% CI: 1.01-2.16, p-value: 0.049) had a higher risk of ICH. Opium-addicted subjects had higher ICH scores (2.61 ± 1.27 vs. 2.11 ± 1.29, p-value: 0.005), were more likely to have infratentorial hemorrhage (22% vs. 12%, OR = 2.13, 95% CI: 1.06-4.28, p-value: 0.038), more likely to be intubated (66% vs. 54%, OR = 1.79, 95% CI: 0.98-3.27, p-value = 0.041) and had lower GCS scores (9.58 ± 3.60 vs. 8.25 ± 3.88, p-value: 0.01). The effect of Opium use disorder independently on ICH was also shown in logistic regression (adjusted OR = 3.15, p-value = 0.001). Conclusion: This study is the first to evaluate the effect of Opium use disorder on ICH, identifying Opium use disorder as a new potential risk factor for ICH. [ABSTRACT FROM AUTHOR]

The COVID-19 (coronavirus disease) pandemic had a severe impact on public health worldwide. A rare but serious complication after administration of adenoviral vaccines against SARS-CoV-2 (AstraZeneca–Oxford and Johnson & Johnson) is vaccine-induced immune thrombotic thrombocytopenia and thrombosis (VITT), which can lead to serious complications such as cerebral venous sinus thrombosis (CVST). CVST itself can cause subarachnoid hemorrhage (SAH) and/or intracerebral hemorrhage (ICH), leading to high mortality due to herniation of brain parenchyma. In those patients, an emergent decompressive hemicraniectomy (DC) is regularly performed. Herein, the authors want to focus on the patients who survive DC following VITT-associated CVST and shed light on the neurosurgical considerations in those patients. We herein propose a treatment algorithm regarding the timing and the perioperative management of cranioplasty. We describe an exemplary case highlighting that special circumstances may result in a more urgent need for autologous cranioplasty than usual, based on individual risk assessment. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is the cerebrovascular disease with the highest disability and mortality rates, causing severe damage to the health of patients and imposing a significant socioeconomic burden. Aging stands as a foremost risk factor for ICH, with a significant escalation in ICH incidence within the elderly demographic, highlighting a close association between ICH and aging. In recent years, with the acceleration of the "aging society" trend, exploring the intricate relationship between aging and ICH has become increasingly urgent and worthy of in-depth attention. We have summarized the characteristics of ICH in the elderly, reviewing how aging influences the onset and development of ICH by examining its etiology and the mechanisms of damage via ICH. Additionally, we explored the potential impacts of ICH on accelerated aging, including its effects on cognitive abilities, quality of life, and lifespan. This review aims to reveal the connection between aging and ICH, providing new ideas and insights for future ICH research. [ABSTRACT FROM AUTHOR]

Objective: The role of MMP-2 in patients with ICH is controversial and the impact of plasma MMP-2 level on clinical outcome is still unclear. Materials and methods: In this study, the peripheral venous blood was acquired from 93 patients with ICH and 88 healthy controls within 24 h of hospitalization and at enrollment. We retrospectively investigated plasma MMP-2 levels of patients and healthy controls. The edema volume, the NIHSS score, the GCS score, and mRS were used to assess and quantify neurological deficit following ICH. Logistic regression analysis was configured to determine the independent relation of plasma MMP-2 levels with clinical outcomes. In addition, the plasma MMP-14 levels and complement C4 level were tested to explore the relationship with plasma MMP-2 level. Results: There was a significant reduction of plasma MMP-2 levels in ICH patients than that in healthy controls (38.02 ± 1.71 vs. 54.03± 2.15, p <0.0001), and MMP- 2 is negatively correlated with the edema volume (r = -0.2187, p <0.05), NIHSS score (r = -0.2194, p < 0.05), blood leucocyte count (r = -0.2549, p = 0.012), and complement C4 level (r = -0.2723, p = 0.005). There is positive correlation between MMP-2 level and GCS score (r = 0.2451, p = 0.01) and MMP-14 level (r = 0.7013, p = 0.005). The multivariate analysis revealed that reduced plasma MMP-2 level is associated with elevated edema volume (OR = 0.2604, 95% CI [0.07 to 0.84], p = 0.02). Conclusion: The plasma MMP-2 level in patients with ICH is significantly lower than that of healthy controls, and plasma MMP-2 level may be a prognostic factor. Plasma MMP-2 levels are correlated with the clinical outcomes of patients and negatively correlated with blood leucocyte count and complement C4 level in patients with ICH. [ABSTRACT FROM AUTHOR]

Objective: To study the prevalence of cognitive impairment in survivors of intracerebral hemorrhage (ICH). Methods: Survivors of spontaneous ICH were followed up in the neurology outpatient department when they reported for follow-up after 6 months. Neuroimaging records at the onset and at follow-up visits are studied for the location of ICH, volume of ICH, intraventricular extension, and hydrocephalus. The volume of ICH is calculated by ABC/2 method on a CT scan. All patients underwent cognitive assessment with Addenbrooke's cognitive examination ACE III and were categorized as patients having cognitive impairment (or) no cognitive impairment. Results: A total of 120 patients were studied, out of which 77 (64%) are males and 43 (36%) are females with age groups ranging from 26 to 75 years. In the study population, the mean age was found to be 62.3 years. Specifically, the mean age for males was 56.9 years, while for females it was 63.4 years. Cognitive impairment was noted in 34 of 120 patients (28%) during 6 to 12 months of examination, of which 11 of 19 were in lobar location, 21 of 94 were in sub-cortical location, and 2 of 7 were in infratentorial location. Conclusion: It was found that 28% of survivors of ICH were cognitively impaired. Hence, it is essential to assess cognition in post-ICH patients during follow-up, so that suitable adjustments can be made in their employment, and also in educating family members in providing a good quality of life. [ABSTRACT FROM AUTHOR]

Background and purpose: This study aimed to investigate the differences in intracerebral hemorrhage (ICH) between Jews and Arabs residing in northern Israel, focusing on risk factors, hemorrhage volume, and functional outcome. Methods: A retrospective analysis was conducted utilizing a population-based registry to investigate intracerebral hemorrhage (ICH) characteristics, risk factors, and outcomes. The registry consisted of inpatients diagnosed with hemorrhagic stroke. Due to the wide variation in data on ICH characteristics and the limited availability of population-based data on predictors of ICH survival and functional outcomes, we collected retrospective data on all adult patients admitted to the Galilee Medical Center with a diagnosis of ICH. Data were obtained from the registry covering the period from 2013 to 2019. Ethnic differences and risk factors associated with intracranial hemorrhage (ICH) were examined within a diverse population of 241 patients, comprising 52.70% Jews (n = 127) and 47.30% Arabs (n = 114). Results: The results of this study revealed significant differences in age, obesity rates, and intracerebral hemorrhage (ICH) location between the two ethnic groups. Hypertension emerged as the most prevalent condition among ICH patients in both ethnic groups (76.70%), followed primarily by anticoagulant use (63.60%), dyslipidemia (60.70%), diabetes (44.60%), obesity (30.60%), smoking (24.60%), and a history of cardiovascular disease (21.80%). Furthermore, 20.90% of the patients had a history of previous cerebrovascular accidents (CVA). Arab patients with ICH were generally younger (62.90 ± 16.00 years) and exhibited higher rates of obesity (38.70%) compared to Jewish patients with ICH (70.17 ± 15.24 years, 23% obesity; p = 0.001, p = 0.013, respectively). Hemorrhage volume was identified as a crucial determinant of patient outcomes, with larger volumes associated with poorer Modified Rankin Scale (mRS) scores at discharge and higher mortality rates. Interestingly, patients without hypertension had higher hemorrhage volumes compared to those with hypertension. The extent of hemorrhage into the ventricles did not significantly correlate with mRS at discharge in our dataset. Conclusions: This study highlights significant differences in the characteristics and outcomes of intracranial hemorrhage (ICH) between Jews and Arabs in northern Israel. The findings reveal variations in age, obesity rates, and ICH location between the two groups. While hypertension was the most prevalent risk factor for both populations, other risk factors differed. Notably, hemorrhage volume emerged as a crucial prognostic factor, aligning with previously published data. These findings underscore the necessity for tailored approaches that consider ethnic-specific factors in the risk assessment, prevention, and management of ICH. Further research is warranted to elucidate the underlying mechanisms and develop interventions aimed at improving outcomes and enhancing healthcare practices in ICH management. [ABSTRACT FROM AUTHOR]

Background and purpose: Intracerebral hemorrhage (ICH) enhances neurogenesis in the subventricular zone (SVZ); however, the mechanism is not fully understood. We investigated the role of brain-derived neurotrophic factor (BDNF) in post-ICH neurogenesis in a rodent model and in patients with ICH using cerebrospinal fluid (CSF). Methods: A rat model of ICH was constructed via stereotaxic injection of collagenase into the left striatum. Patients with ICH receiving an external ventricular drain were prospectively enrolled. CSF was collected from rats and patients at different post-ICH times. Primary cultured rat neural stem cells (NSCs) were treated with CSF with or without BDNF-neutralized antibody. Immunohistochemistry and immunocytochemistry were used to detect NSC proliferation and differentiation. The BDNF concentration in CSF was quantified using enzyme-linked immunosorbent assays (ELISA). Results: In the rat model of ICH, the percentage of proliferating NSCs and neuroblasts in SVZ was elevated in bilateral hemispheres. The cultured rat NSCs treated with CSF from both rats and patients showed an increased capacity for proliferation and differentiation toward neuroblasts. BDNF concentration was higher in CSF collected from rats and patients with ICH than in controls. Blocking BDNF decreased the above-noted promotion of proliferation and differentiation of cultured NSCs by CSF treatment. In patients with ICH, the BDNF concentration in CSF and the neurogenesis-promoting capacity of post-ICH CSF correlated positively with ICH volume. Conclusion: BDNF in CSF contributes to post-ICH neurogenesis, including NSC proliferation and differentiation toward neuroblasts in a rat model and patients with ICH. [ABSTRACT FROM AUTHOR]

Background: Intracerebral hemorrhage (ICH) is a potentially devastating condition with elevated early mortality rates, poor functional outcomes, and high costs of care. Standard of care involves intensive supportive therapy to prevent secondary injury. To date, there is no randomized control study demonstrating benefit of early evacuation of supratentorial ICH. Methods: The Early Minimally Invasive Removal of Intracerebral Hemorrhage (ENRICH) Trial was designed to evaluate the minimally invasive trans-sulcal parafascicular surgery (MIPS) approach, a technique for safe access to deep brain structures and ICH removal using the BrainPath® and Myriad® devices (NICO Corporation, Indianapolis, IN). ENRICH is amulti-centered, two-arm, randomized, adaptive comparative-effectiveness study, where patients are block randomized by ICH location and Glasgow Coma Score (GCS) to early ICH evacuation using MIPS plus standard guideline-basedmanagement vs. standardmanagement alone to determine if MIPS results in improved outcomes defined by the utility-weighted modified Rankin score (UWmRS) at 180 days as the primary endpoint. Secondary endpoints include clinical and economic outcomes of MIPS using cost per quality-adjusted life years (QALYs). The inclusion and exclusion criteria aim to capture a broad group of patients with high riskof significant morbidity and mortality to determine optimal treatment strategy. Discussion: ENRICH will result in improved understanding of the benefit of MIPS for both lobar and deep ICH affecting the basal ganglia. The ongoing study will lead to Level-I evidence to guide clinicians treatment options in the management of acute treatment of ICH. [ABSTRACT FROM AUTHOR]

Current primary intracerebral hemorrhage (ICH) treatments focus on limiting hematoma volume by lowering blood pressure, reversing anticoagulation, or hematoma evacuation. Nevertheless, there is no effective strategy to protect the brain from secondary injury due to ICH. Excess heme and iron as by-products of lysing clots in ICH might contribute to this secondary injury by triggering perihematomal edema. We present a clinical situation of an ICH case where iron-chelating therapy might be beneficial, as supported by scientific evidence. We looked through four databases (Pubmed, Cochrane, Embase, and Google Scholar) to find studies assessing the efficacy of iron-chelating therapy in ICH patients. Validity, importance, and applicability (VIA) of the included articles were appraised using worksheets from the Oxford Centre for Evidence-Based Medicine. Two out of five eligible studies were valid, important, and applicable to our patient. Both studies showed the positive effects of iron-chelating therapy on neurological outcome, as measured by National Institutes of Health Stroke Scale (NIHSS) score and modified Rankin Score (mRS). The beneficial effects of deferoxamine were demonstrated within the moderate volume (10–30 mL) subgroup, with a positive relative risk reduction (RRR) and low number needed to treat (six persons). Based on our appraisal, we considered iron-chelating therapy as an additional therapy for ICH patients, given its benefits and adverse effects. More specific studies using a larger sample size, focusing on moderate-volume ICH, and using standardized neurological outcomes are encouraged. [ABSTRACT FROM AUTHOR]

Background: Chinese medicine usually acts as "multi-ingredients, multi-targets and multi-pathways" on complex diseases, and these action modes reflect the coordination and integrity of the treatment process with traditional Chinese medicine (TCM). System pharmacology is developed based on the cross-disciplines of directional pharmacology, system biology, and mathematics, has the characteristics of integrity and synergy in the treatment process of TCM. Therefore, it is suitable for analyzing the key ingredients and mechanisms of TCM in treating complex diseases. Intracerebral Hemorrhage (ICH) is one of the leading causes of death in China, with the characteristics of high mortality and disability rate. Bring a significant burden on people and society. An increasing number of studies have shown that Chinese medicine prescriptions have good advantages in the treatment of ICH, and Ditan Decoction (DTT) is one of the commonly used prescriptions in the treatment of ICH. Modern pharmacological studies have shown that DTT may play a therapeutic role in treating ICH by inhibiting brain inflammation, abnormal oxidative stress reaction and reducing neurological damage, but the specific key ingredients and mechanism are still unclear. Methods: To solve this problem, we established PPI network based on the latest pathogenic gene data of ICH, and CT network based on ingredient and target data of DTT. Subsequently, we established optimization space based on PPI network and CT network, and constructed a new model for node importance calculation, and proposed a calculation method for PES score, thus calculating the functional core ingredients group (FCIG). These core functional groups may represent DTT therapy for ICH. Results: Based on the strategy, 44 ingredients were predicted as FCIG, results showed that 80.44% of the FCIG targets enriched pathways were coincided with the enriched pathways of pathogenic genes. Both the literature and molecular docking results confirm the therapeutic effect of FCIG on ICH via targeting MAPK signaling pathway and PI3K-Akt signaling pathway. Conclusions: The FCIG obtained by our network pharmacology method can represent the effect of DTT in treating ICH. These results confirmed that our strategy of active ingredient group optimization and the mechanism inference could provide methodological reference for optimization and secondary development of TCM. [ABSTRACT FROM AUTHOR]

Magnetic Induction Spectroscopy (MIS) is an emerging technique for contactless measurement of bioimpedance with promising application in intracerebral hemorrhage (ICH) detection. Here, we report numerical simulations of ICH detection based on the MIS. A novel MIS sensor using two planar rectangular spiral coils (TPRSC) as the exciter with frequency range 120 kHz-9 MHz is proposed for the first time. The exciter can generate an antisymmetric normal magnetic field at the detection sensor, and hence the primary voltage can be canceled theoretically. We construct symmetry-based and asymmetry-based ICH models with realistic anatomic structure and hexahedral discretization feature for numerical simulations. The numerical simulations based on the finite integration technique are conducted in the three-dimensional electromagnetic analysis software CST. The voltage phase spectrum, the phase change spectrum and the relative conductivity change spectrum at different hemorrhage volumes are calculated. We compare sensitivities between the TPRSC-based MIS sensor and the conventional type (CC MIS sensor) which uses the single planar rectangular spiral coil as the exciter. Using the constructed ICH models, the specific absorption rate (SAR) and the internal electric field strength are computed to evaluate the electromagnetic safety of the TPRSC-based MIS sensor. Results show that compared with the CC MIS sensor, the sensitivity of the TPRSC-based MIS sensor for measuring the voltage phase is improved by two orders of magnitude, and for measuring the phase change is improved by more than ten times. The phase change and relative conductivity change spectra for the TPRSC-based MIS sensor demonstrate good separability between different small-volume hemorrhages. In addition, the electromagnetic safety of the TPRSC-based MIS is also superior to that of the CC MIS sensor, which conforms to the IEEE standard and the ICNRP guidelines over a wide range of the amplitude of the excitation current. [ABSTRACT FROM AUTHOR]

The method of iron-dependent cell death known as ferroptosis is distinct from apoptosis. The suppression of ferroptosis after intracerebral hemorrhage (ICH) will effectively treat ICH and improve prognosis. This paper primarily summarizes the mechanism of ferroptosis after ICH, with an emphasis on lipid peroxidation, the antioxidant system, iron metabolism, and other pathways. In addition, regulatory targets and drug molecules were described. Although there has been some progress in the field of study, there are still numerous gaps. The mechanism by which non-heme iron enters neurons through the blood–brain barrier (BBB), the mitochondrial role in ferroptosis, and the specific mechanism by which lipid peroxidation induces ferroptosis remain unclear and require further study. In addition, the inhibitory effect of many drugs on ferroptosis after ICH has only been demonstrated in basic experiments and must be translated into clinical trials. In summary, research on ferroptosis following ICH will play an important role in the treatment of ICH. [ABSTRACT FROM AUTHOR]

Background: Early hematoma growth is associated with poor functional outcomes in patients with intracerebral hemorrhage (ICH). We aimed to explore whether quantitative hematoma heterogeneity in non-contrast computed tomography (NCCT) can predict early hematoma growth. Methods: We used data from the Risk Stratification and Minimally Invasive Surgery in Acute Intracerebral Hemorrhage (Risa-MIS-ICH) trial. Our study included patients with ICH with a time to baseline NCCT <12 h and a follow-up CT duration <72 h. To get a Hounsfield unit histogram and the coefficient of variation (CV) of Hounsfield units (HUs), the hematoma was segmented by software using the auto-segmentation function. Quantitative hematoma heterogeneity is represented by the CV of hematoma HUs. Multivariate logistic regression was utilized to determine hematoma growth parameters. The discriminant score predictive value was assessed using the area under the ROC curve (AUC). The best cutoff was determined using ROC curves. Hematoma growth was defined as a follow-up CT hematoma volume increase of >6mL or a hematoma volume increase of 33% compared with the baseline NCCT. Results: A total of 158 patients were enrolled in the study, of which 31 (19.6%) had hematoma growth. The multivariate logistic regression analysis revealed that time to initial baseline CT (P = 0.040, odds ratio [OR]: 0.824, 95 % confidence interval [CI]: 0.686-0.991), "heterogeneous" in the density category (P = 0.027, odds ratio [OR]: 5.950, 95 % confidence interval [CI]: 1.228-28.828), and CV of hematoma HUs (P = 0.018, OR: 1.301, 95 % CI: 1.047-1.617) were independent predictors of hematoma growth. By evaluating the receiver operating characteristic curve, the CV of hematoma HUs (AUC = 0.750) has a superior predictive value for hematoma growth than for heterogeneous density (AUC = 0.638). The CV of hematoma HUs had an 18% cutoff, with a specificity of 81.9 % and a sensitivity of 58.1 %. Conclusion: The CV of hematoma HUs can serve as a quantitative hematoma heterogeneity index that predicts hematoma growth in patients with early ICH independently. [ABSTRACT FROM AUTHOR]

Background and Objectives: Treatment-limiting decisions (TLDs) are employed to actively withhold treatment/invasive interventions from patients in whom clinicians feel they would derive little to no benefit and/or suffer detrimental effects. Data regarding the employment of TLDs in patients with spontaneous intracerebral hemorrhage (ICH) remain sparse. Accordingly, this study sought to investigate both the prevalence of TLDs and factors driving TLDs in patients suffering from spontaneous ICH. Materials and Methods: This was a retrospective study of 249 consecutive patients with ICH treated from 2018–2019 at the Neurovascular Center of the University Hospital Bonn. Reasons deemed critical in the decision-making process with regard to TLD were ultimately extracted/examined via chart review of qualifying patients. Results: A total of 249 patients with ICH were included within the final analyses. During the time period examined, 49 patients (20%) had advanced directives in place, whereas in 53 patients (21%) consultation with relatives or acquaintances was employed before further treatment decisions. Overall, TLD ultimately manifested in 104 patients (42%). TLD was reached within 6 h after admission in 52 patients (50%). Congruent with severity of injury and expected outcomes, TLDs were more likely in patients with signs of cerebral herniation and an ICH score > 3 (p < 0.001). Conclusions: The present study examines details associated with TLDs in patients with spontaneous ICH. These data provide insight into key decisional processes and reinforce the need for further structured investigations in an effort to help guide patients and their families. [ABSTRACT FROM AUTHOR]

Background: In patients with spontaneous supratentorial intracerebral hemorrhage (ICH), open craniotomy has failed to improve a functional outcome. Innovative minimally invasive neurosurgery (MIS) may improve a health outcome and reduce healthcare costs. Aims: Before starting phase-III trials, we aim to assess conditions that need to be met to reach the potential cost-effectiveness of MIS compared to usual care in patients with spontaneous supratentorial ICH. Methods: We used a state-transition model to determine at what effectiveness and cost MIS would become cost-effective compared to usual care in terms of quality-adjusted life-years (QALYs) and direct healthcare costs. Threshold and two-way sensitivity analyses were used to determine the minimal effectiveness and maximal costs of MIS, and the most cost-effective strategy for each combination of cost and effectiveness. Scenario and probabilistic sensitivity analyses addressed model uncertainty. Results: Given €10,000 of surgical costs, MIS would become cost-effective when at least 0.7–1.3% of patients improve to a modified Rankin Scale (mRS) score of 0–3 compared to usual care. When 11% of patients improve to mRS 0–3, surgical costs may be up to €83,301–€164,382, depending on the population studied. The cost-effectiveness of MIS was mainly determined by its effectiveness. In lower mRS states, MIS needs to be more effective to be cost-effective compared to higher mRS states. Conclusion: MIS has the potential to be cost-effective in patients with spontaneous supratentorial ICH, even with relatively low effectiveness. These results support phase-III trials to investigate the effectiveness of MIS. [ABSTRACT FROM AUTHOR]

Introduction: The role of commensal microbiota in systemic diseases, including brain diseases, has attracted increasing attention. Oral infectious diseases, such as dental caries and periodontitis, are also involved in cerebrovascular diseases and cognitive impairment. Cerebral microbleeds (CMBs) and intracerebral hemorrhage due to small vessel disease (SVD), are presumably associated with a high risk of vascular cognitive impairment and stroke. We previously reported that Streptococcus mutans (S. mutans , the main pathogen of dental caries), harboring the cnm gene that encodes the collagen-binding protein Cnm, is associated with the development of hypertensive intracerebral hemorrhage and aggravation of CMBs. We also proposed a mechanism by which the circulating Cnm-expressing S. mutans causes intracerebral hemorrhage or CMBs; it binds to denuded basement membranes mainly composed of collagen IV through damaged tight junctions or it directly invades endothelial cells, resulting in blood-brain barrier injury. In November 2018, we initiated a multicenter, prospective cohort study (RAMESSES: Risk Assessment of Cnm-positive S. mutans in Stroke Survivors; UMIN Clinical Trials Registry: UMIN000045559) to explore the longitudinal association between Cnm-positive S. mutans and CMBs with comprehensive dental findings, which should determine the effect of Cnm-positive S. mutans in the oral cavity on the risk of CMB development and cognitive decline. Methods: Fifteen domestic institutes will be enlisted to enroll 230 patients who have at least one CMB in the deep brain area and develop a stroke within the past year. The prevalence of Cnm-positive S. mutans based on oral specimens and dental hygiene will be examined. The primary outcome is the number of newly developed deep CMBs. The secondary outcomes include the new development of lobar, subtentorial, or any type of CMBs; symptomatic intracerebral hemorrhage or ischemic stroke; changes in cognitive function or frailty; major bleeding; all-cause mortality; and antibody titers against periodontal pathogens. The observation period will be 2 years. Discussion: The 2-year longitudinal prospective cohort study is expected to establish the role of Cnm-positive S. mutans in SVD including CMBs and intracerebral hemorrhage from the perspective of the "brain-oral axis" and provide guidance for novel prophylactic strategies against Cnm-positive S. mutans -induced SVD. [ABSTRACT FROM AUTHOR]

Background: Chinese herbal medicine (CHM) is characterized by "multi-compounds, multi-targets and multipathway", which has advanced benefits for preventing and treating complex diseases, but there still exists unsolved issues, mainly include unclear material basis and underlying mechanism of prescription. Integrated pharmacology is a hot cross research area based on system biology, mathematics and poly-pharmacology. It can systematically and comprehensively investigate the therapeutic reaction of compounds or drugs on pathogenic genes network, and is especially suitable for the study of complex CHM systems. Intracerebral Hemorrhage (ICH) is one of the main causes of death among Chinese residents, which is characterized with high mortality and high disability rate. In recent years, the treatment of ICH by CHM has been deeply researched. Xue Fu Zhu Yu Decoction (XFZYD), one of the commonly used prescriptions in treating ICH at clinic level, has not been clear about its mechanism. Methods: Here, we established a strategy, which based on compounds-targets, pathogenetic genes, network analysis and node importance calculation. Using this strategy, the core compounds group (CCG) of XFZYD was predicted and validated by in vitro experiments. The molecular mechanism of XFZYD in treating ICH was deduced based on CCG and their targets. Results: The results show that the CCG with 43 compounds predicted by this model is highly consistent with the corresponding Compound-Target (C-T) network in terms of gene coverage, enriched pathway coverage and accumulated contribution of key nodes at 89.49%, 88.72% and 90.11%, respectively, which confirmed the reliability and accuracy of the effective compound group optimization and mechanism speculation strategy proposed by us. Conclusions: Our strategy of optimizing the effective compound groups and inferring the mechanism provides a strategic reference for explaining the optimization and inferring the molecular mechanism of prescriptions in treating complex diseases of CHM. [ABSTRACT FROM AUTHOR]

The main purpose of the study was to explore a reliable way to automatically handle emergency cases, such as intracerebral hemorrhage (ICH). Therefore, an artificial intelligence (AI) system, named, H-system, was designed to automatically recognize medical text data of ICH patients and output the treatment plan. Furthermore, the efficiency and reliability of the H-system were tested and analyzed. The H-system, which is mainly based on a pretrained language model Bidirectional Encoder Representations from Transformers (BERT) and an expert module for logical judgment of extracted entities, was designed and founded by the neurosurgeon and AI experts together. All emergency medical text data were from the neurosurgery emergency electronic medical record database (N-eEMRD) of the First Affiliated Hospital of Chongqing Medical University, Chongqing Emergency Medical Center, and Chongqing First People's Hospital, and the treatment plans of these ICH cases were divided into two types. A total of 1,000 simulated ICH cases were randomly selected as training and validation sets. After training and validating on simulated cases, real cases from three medical centers were provided to test the efficiency of the H-system. Doctors with 1 and 5 years of working experience in neurosurgery (Doctor-1Y and Doctor-5Y) were included to compare with H-system. Furthermore, the data of the H-system, for instance, sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and the area under the receiver operating characteristics curve (AUC), were calculated and compared with Doctor-1Y and Doctor-5Y. In the testing set, the time H-system spent on ICH cases was significantly shorter than that of doctors with Doctor-1Y and Doctor-5Y. In the testing set, the accuracy of the H-system's treatment plan was 88.55 (88.16–88.94)%, the specificity was 85.71 (84.99–86.43)%, and the sensitivity was 91.83 (91.01–92.65)%. The AUC value of the H-system in the testing set was 0.887 (0.884–0.891). Furthermore, the time H-system spent on ICH cases was significantly shorter than that of doctors with Doctor-1Y and Doctor-5Y. The accuracy and AUC of the H-system were significantly higher than that of Doctor-1Y. In addition, the accuracy of the H-system was more closed to that of Doctor-5Y. The H-system designed in the study can automatically recognize and analyze medical text data of patients with ICH and rapidly output accurate treatment plans with high efficiency. It may provide a reliable and novel way to automatically and rapidly handle emergency cases, such as ICH. [ABSTRACT FROM AUTHOR]

Introduction and Aim: Data remain limited on sex-differences in patients with oral anticoagulant (OAC)-related intracerebral hemorrhage (ICH). We aim to explore similarities and differences in risk factors, acute presentation, treatments, and outcome in men and women admitted with OAC-related ICH. Method: This study was a retrospective observational study based on 401 consecutive patients with OAC-related ICH admitted within 24 h of symptom onset. The study was registered on osf.io. We performed logarithmic regression and cox-regression adjusting for age, hematoma volume, Charlson Comorbidity Index (CCI), and pre-stroke modified Ranking Scale (mRS). Gender and age were excluded from CHA2DS2-VASc and CCI was not adjusted for age. Results: A total of 226 men and 175 women were identified. More men were pre-treated with vitamin K-antagonists (73.5% men vs. 60.6% women) and more women with non-vitamin K-antagonist oral anticoagulants (26.5% men vs. 39.4% women), p = 0.009. Women were older (mean age 81.9 vs. 76.9 years, p < 0.001). CHA2DS2-VASc and CCI were similar in men and women. Hematoma volumes (22.1 ml in men and 19.1 ml in women) and National Institute of Health Stroke Scale (NIHSS) scores (13 vs. 13) were not statistically different, while median Glasgow Coma Scale (GCS) was lower in women, (14 [8;15] vs. 14 [10;15] p = 0.003). Women's probability of receiving reversal agents was significantly lower (adjusted odds ratio [ aOR ] = 0.52, p = 0.007) but not for surgical clot removal (aOR = 0.56, p = 0.25). Women had higher odds of receiving do-not-resuscitate (DNR) orders within a week (aOR = 1.67, p = 0.04). There were no sex-differences in neurological deterioration (aOR = 1.48, p = 0.10), ability to walk at 3 months (aOR = 0.69, p = 0.21) or 1-year mortality (adjusted hazard ratio = 1.18, p = 0.27). Conclusion: Significant sex-differences were observed in age, risk factors, access to treatment, and DNRs while no significant differences were observed in comorbidity burden, stroke severity, or hematoma volume. Outcomes, such as adjusted mortality, ability to walk, and neurological deterioration, were comparable. This study supports the presence of sex-differences in risk factors and care but not in presentation and outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether spectral detector CT (SDCT) with a plain non-enhanced monochromatic CT, a water-weighted image after iodine removal, an iodine map, and Mono energetic images changes the diagnosis and classification of intracranial hemorrhage based on single energy CT after endovascular treatment (EVT) for ischemic stroke. Methods: Two readers evaluated single energy and SD CT data collected from 63 patients within one week after EVT. They diagnosed ICH or contrast staining, and graded ICH according to the Heidelberg and Safe Implementation of Thrombolysis in Stroke–Monitoring Study (SITS-MOST) classification. Differences in diagnosis between single energy and SD CT were tested with Pearson's chi-squared test. Diagnostic values of single energy CT were calculated. Interrater agreement was based on Cohen's Kappa. Results: When spectral data were added to single energy CT, the diagnosis of ICH changed in 8 CT scans (13%): in 4, the diagnosis of ICH was rejected and in 4, initially undetected ICH was diagnosed. In an additional 3 patients, the ICH grade was modified. CT alone had 88% sensitivity, 87% specificity, 88% positive diagnostic value, 87% negative diagnostic value, and 87% overall accuracy for ICH compared to SDCT. Interreader agreement on the presence of ICH was 0.84 (95% CI 0.51–0.86) for spectral CT and 0.84 (95% CI 0.73–0.97) for single energy CT. Conclusion: SD CT after endovascular treatment contributes to the distinction between intracranial hemorrhage and contrast staining. [ABSTRACT FROM AUTHOR]

The Alberta Stroke Program Early CT Score (ASPECTS) is widely used to guide thrombolytic therapy and predict the functional outcome of patients with acute ischemic stroke (AIS). Whether ASPECTS can predict the functional outcome of patients with intracerebral hemorrhage (ASPECTS-H) remains unclear. Patients with primary intracerebral hemorrhage (ICH) were collected and retrospectively analyzed. ASPECTS-H was assessed at admission. Patients were followed up at 30 days and 90 days after the onset of ICH. Occurrence of death within 90 days after ICH was the primary endpoint. Modified Rankin Scale (mRS) ≥ 3 was considered a poor functional outcome. A total of 149 patients met eligibility criteria; 61 (40.9%) had poor functional outcome at 30 days, and 37 (24.8%) had poor functional outcome at 90 days. Using binary logistic regression modeling, we found that a low ASPECTS-H was associated with a poor functional outcome. The risk ratio of a low ASPECTS-H was 2.31 at 30 days (P = 0.000; 95% CI, 1.560–3.421) and 2.711 at 90 days (P = 0.000; 95% CI, 1.677–4.381). The optimal cutoff value of ASPECTS-H to discriminate good and poor 30-day and 90-day outcomes was 7.5 (Sensitivity30-day = 0.636, 1-Specificity30 – day = 0.311; Sensitivity90-day = 0.580, 1-Specificity90-day = 0.270). A low ASPECTS-H was an indicator of poor short-term and long-term functional outcomes of ICH. [ABSTRACT FROM AUTHOR]

Isorhynchophylline (IRN), a component of traditional Chinese herb Uncaria rhynchophylla, possesses strong antioxidant activity. Ferroptosis induced by iron overload causes cell oxidative stress after intracerebral hemorrhage (ICH). Therefore, this study aims to explore the effects of IRN on the ferroptosis following ICH. In this study, mouse hippocampal HT-22 cells were treated with ferric ammonium citrate (FAC) alone or together with IRN, and we found IRN reduced the FAC-induced cell damage. Then, cells were treated with IRN following treatment with FAC after transfection with miR-122-5p inhibitor, and the results showed IRN reduced the FAC-induced decrease of miR-122-5p levels and relieved the ferroptosis by detecting ferroptotic marker proteins, iron ion concentration and oxidative stress level; after transfection with miR-122-5p inhibitor, the protective effects of IRN against FAC-induced ferroptosis in these cells were weakened. TP53 (also known as p53) was verified as a target of miR-122-5p by using dual luciferase reporter assay, and restoration of TP53 attenuated the effects of miR-122-5p on ferroptotic marker proteins expression, iron ion concentration and lipid ROS levels, as well as solute carrier family seven member 11 (SLC7A11) mRNA expression. SLC7A11 siRNA reversed the inhibitory effects of IRN on FAC-induced ferroptosis and oxidative stress levels. Subsequently, IRN increased the mNSS score, and decreased brain water content and EB content in ICH model. Moreover, IRN decreased ferroptosis and lipid ROS level, upregulated the expression of miR-122-5p and SLC7A11 mRNA, and inhibited TP53 expression. Our findings reveal that IRN protects neurocyte from ICH-induced ferroptosis via miR-122-5p/TP53/SLC7A11 pathway, which may provide a potential therapeutic mechanism for ICH. [ABSTRACT FROM AUTHOR]

Background and Objective: Clinicians working in intensive care frequently report perceptions of inappropriate care (PIC) situations. Intracerebral haemorrhage (ICH) is associated with high rates of mortality and morbidity. Prognosticating after ICH is complex and may be influenced by clinicians' subjective impressions and biases, which may, in turn, influence decision making regarding the level of care provided. The aim of this study was to qualitatively explore perceptions of neurocritical care in relation to the expected functional outcome for ICH patients. Design: Qualitative study using semi-structured interviews with neurocritical care doctors and nurses. Setting: Neurocritical care (NCC) department in a UK neuroscience tertiary referral center. Subjects: Eleven neurocritical care nurses, five consultant neurointensivists, two stroke physicians, three neurosurgeons. Intervention: None. Measurements and Main Results: We conducted 21 semi-structured interviews and identified five key themes: (1) prognostic uncertainty (2) subjectivity of good versus poor outcome (3) perceived inappropriate care (PIC) situations (including for frail elderly patients) (4) challenging nature of decision-making (5) clinician distress. Conclusions: Caring for severely affected ICH patients in need of neurocritical care is challenging, particularly with frail elderly patients. Awareness of the challenges could facilitate interventions to improve decision-making for this group of stroke patients and their families, as well as measures to reduce the distress on clinicians who care for this patient group. Our findings highlight the need for effective interdisciplinary shared decision making involving the family, taking into account patients' previously expressed values and preferences and incorporating these into bespoke care planning. [ABSTRACT FROM AUTHOR]

As a selective inhibitor of mitochondrial fission protein dynamin-related protein-1 (Drp1), mitochondrial division inhibitor 1 (mdivi-1) can cross the blood–brain barrier (BBB) and exert neuroprotection. However, it remains unclear whether mdivi-1 can attenuate intracerebral hemorrhage (ICH)-induced secondary brain injury. This study was undertaken to characterize the roles of mdivi-1 in short-term and long-term behavioral outcomes, along with synaptic plasticity changes in mice after ICH. The results indicated mdivi-1 reversed Drp1 translocation and the morphologic changes of mitochondria, as well as ameliorated short-term neurobehavioral deficits, the BBB disruption and brain edema remarkably. In addition, mdivi-1 could rescue ICH-induced motor and memory dysfunctions. Mdivi-1 could also prevent ICH-induced reductions in synaptic proteins (synapsin I, PSD95) and phosphorylated cAMP-response element binding (p-CREB). In vitro, mdivi-1 inhibited hemin-induced hippocampal neuron death and improved neurite outgrowth. In conclusion, we found that mdivi-1 can alleviate short-term and long-term neurological deficits, synaptic dysfunction. These findings demonstrate that mdivi-1 may be beneficial in the treatment of secondary brain injury, synaptic dysfunction and neurological outcomes caused by ICH. [ABSTRACT FROM AUTHOR]

This study aims at evaluating the importance and its underlying mechanism of the cluster of microRNA-144/451 (miR-144/451) in the models with intracerebral hemorrhage (ICH). A model of collagenase-induced mice with ICH and a model of mice with simple miR-144/451 gene knockout (KO) were used in this study. Neurodeficits and the water content of the brain of the mice in each group were detected 3 days after collagenase injection. The secretion of proinflammatory cytokines, such as tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β), as well as certain biomarkers of oxidative stress, was determined in this study. The results revealed that the expression of miR-451 significantly decreased in the mice with ICH, whereas miR-144 showed no significant changes. KO of the cluster of miR-144/451 exacerbated the neurological deficits and brain edema in the mice with ICH. Further analyses demonstrated that the KO of the cluster of miR-144/451 significantly promoted the secretion of TNF-α and IL-1β and the oxidative stress in the perihematomal region of the mice with ICH. In addition, the miR-144/451's depletion inhibited the regulatory axis' activities of miR-451-14-3-3ζ-FoxO3 in the mice with ICH. In conclusion, these data demonstrated that miR-144/451 might protect the mice with ICH against neuroinflammation and oxidative stress by targeting the pathway of miR-451-14-3-3ζ-FoxO3. [ABSTRACT FROM AUTHOR]

Objective: Hypertension is the commonest cause of acute spontaneous intracerebral hemorrhage (ICH) which is life-threatening with a poor prognosis. The aim of this study is to evaluate the prognosis and blood pressure monitoring and control in patients presented by acute spontaneous ICH. Methods: One hundred and fifty patients presented by acute spontaneous ICH were classified according to the modified Rankin Scale (mRS) score after discharge to 70 patients with better outcomes (mRS = 0–2) while 80 patients with poor outcome (mRS = 3–6). Independent factors that were significantly related to prognosis were assessed by multivariate logistic regression. Spearman's correlation of the blood pressure monitoring in the acute ICH and the outcome was investigated. Results: Systolic blood pressure at the onset of ICH was higher in the unfavorable outcome group (P = 0.009). Diastolic blood pressure 1 h after admission, systolic blood pressure 6 h after admission, and the systolic blood pressure 24 h after admission to hospital were lower in the favorable outcome group (P = 0.005, P = 0.007 and 0.01, respectively). The independent variables related to favorable outcomes were younger age patients (P = 0.004), better level of consciousness at admission to hospital (P = 0.0001), and lower systolic blood pressure 6 h after admission to hospital (P = 0.005), decreased volume of hematoma (P = 0.05), supratentorial ICH (P = 0.02), and absence of intraventricular hemorrhage (P = 0.02). Conclusions: Proper control and monitoring of the blood pressure in acute intracerebral hemorrhage must be initiated immediately especially in the first 6 h after hospitalization. Trial registration: ClinicalTrials.gov ID: NCT04191863 'Retrospectively registered' [ABSTRACT FROM AUTHOR]

Background and Purpose: We aimed to determine whether dual-energy CT (DECT) follow-up can differentiate contrast staining (CS) from intracranial hemorrhage (ICH) in stroke patients treated with intravenous thrombolysis (IVT), who had undergone acute stroke imaging using CT angiography (CTA), and CT perfusion (CTP). Materials and Methods : Between November 2012 and January 2018, 168 patients at our comprehensive stroke center underwent DECT follow-up within 36 h after IVT and acute CTA with or without CTP but did not receive intra-arterial imaging or treatment. Two independent readers evaluated plain monochromatic CT (pCT) alone and compared this with a second reading of a combined DECT approach using pCT and water- and iodine-weighted images, establishing and grading the ICH diagnosis, per Heidelberg and Safe Implementation of Treatments in Stroke Monitoring Study (SITS-MOST) classifications. Results: On pCT alone within 36 h, 31/168 (18.5%) patients had findings diagnosed as ICH. Using combined DECT (cDECT) changed ICH diagnosis to "CS only" in 3/168 (1.8%) patients, constituting 3/31 (9.7%) of cases with initially pCT-diagnosed ICH. These three cases had pCT diagnoses of one SAH, one minor, and one more extensive petechial hemorrhage (hemorrhagic infarction types 1 and 2), respectively. pCT alone had a 100% sensitivity, 98% specificity, 90% positive predictive value (PPV), 100% negative predictive value (NPV), and 98% accuracy for any ICH, compared to the cDECT. Inter-reader agreement for ICH classification using pCT compared to DECT was weighted kappa 0.92 (95% CI 0.87–0.98) vs. 0.91 (0.85–0.95). Conclusion: Compared to pCT, DECT within 36 h after IV thrombolysis for acute ischemic stroke, changes the radiological diagnosis of post-treatment ICH to "CS only" in a small proportion of patients. Studies are warranted of whether the altered radiological reports have an impact on patient management, for example initiation timing of antithrombotic secondary prevention. [ABSTRACT FROM AUTHOR]

Background: Quantitative susceptibility mapping (QSM) offers a means to track iron evolution in hemorrhage. However, standard QSM sequences have long acquisition times and are prone to motion artifact in hemorrhagic patients.Purpose: To minimize motion artifact and acquisition time by performing rapid QSM in intracerebral hemorrhage (ICH) using single-shot echo planar imaging (EPI).Study Type: Prospective method evaluation.Population/subjects: Forty-five hemorrhages were analyzed from 35 MRI exams obtained between February 2016 and March 2019 from 27 patients (14 male / 13 female, age: 71 ± 12 years) with confirmed primary ICH.Field Strength/sequence: 3T; susceptibility-weighted imaging (SWI) with 4.54-minute acquisition and 2D single-shot gradient EPI with 0.45-minute acquisition.Assessment: Susceptibility maps were constructed from both methods. Measurement of ICH area and mean magnetic susceptibility were made manually by three independent observers. Motion artifacts were quantified using the magnitude signal ratio of artifact-to-brain tissue to classify into three categories: mild or no artifact, moderate artifact, or severe artifact. The cutoff for each category was determined by four observers.Statistical Tests: Pearson's correlation coefficient and paired t-test using α = 0.05 were used to compare results. Inter- and intraclass correlation was used to assess observer variability.Results: Using 45 hemorrhages, the ICH regions measured on susceptibility maps obtained from EPI and SWI sequences had high correlation coefficients for area (R2  ≥ 0.97) and mean magnetic susceptibility (R2  ≥ 0.93) for all observers. The artifact-to-tissue ratio was significantly higher (P < 0.01) for SWI vs. EPI, and the standard deviation for the SWI method (SD = 0.05) was much larger than EPI (SD = 0.01). All observers' measurements showed high agreement.Data Conclusion: Single-shot EPI-QSM enabled rapid measurement of ICH area and mean magnetic susceptibility, with reduced motion as compared with more standard SWI. EPI-QSM requires minimal additional acquisition time and could be incorporated into iron tracking studies in ICH.Level Of Evidence: 2 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;51:712-718. [ABSTRACT FROM AUTHOR]

Cell death is deeply involved in pathophysiology of brain injury after intracerebral hemorrhage (ICH). Necroptosis, one of the recently discovered forms of cell death, plays an important role in various diseases, including ICH. Previous studies have suggested that a considerable number of neurons undergoes necroptosis after ICH. However, necroptosis of microglia after ICH has not been reported to date. The present study demonstrated for the first time that necroptosis occurred in the microglia surrounding the hematoma after ICH in C57 mice, and melatonin, a hormone that is predominantly synthesized in and secreted from the pineal gland, exerted a neuroprotective effect by suppressing this process. When we further explored the potential underlying mechanism, we found that melatonin inhibits RIP3-mediated necroptosis by regulating the deubiquitinating enzyme A20 (also known as TNFAIP3) expression after ICH. In summary, we have demonstrated the role of microglial necroptosis in the pathogenesis of ICH. More importantly, A20 was identified as a novel target of melatonin, which opens perspectives for future research. [ABSTRACT FROM AUTHOR]

Inflammation and apoptosis are two key factors contributing to secondary brain injury after intracerebral hemorrhage (ICH). In the present study, we explored the neuroprotective role of methylene blue (MB) in ICH rats and studied the potential mechanisms involved. Rats were subjected to local injection of collagenase IV in the striatum or sham surgery. We observed that MB treatment could exert a neuroprotective effect on ICH by promoting neurological scores, decreasing the brain water content, alleviating brain–blood barrier disruption, and improving the histological damages in the perihematomal areas. Furthermore, we demonstrated that the various mechanisms underlying MB's neuroprotective effects linked to inhibited apoptosis and inhibited neuroinflammation. In addition, wortmannin, a selective inhibitor of phosphoinositide 3‐kinase (PI3K), could reverse the antiapoptotic and anti‐inflammatory effects of MB, which suggested that the PI3K–Akt pathway played an important role. In conclusion, these data suggested that MB could inhibit apoptosis and ameliorate neuroinflammation after ICH, and its neuroprotective effects might be exerted via the activation of the PI3K/Akt/GSK3β pathway. Methylene blue (MB) could inhibit apoptosis and ameliorate neuroinflammation after ICH, and its neuroprotective effects might be exerted via the activation of the PI3K/Akt/GSK3β pathway. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) have emerged as an important class of molecules that have been associated with brain function and neurological disease, but the expression profiles of lncRNAs after intracerebral hemorrhage (ICH) remain to be elucidated. In this study, we determined the expression pattern of nuclear factor‐k‐gene binding (NF‐kB) interacting lncRNA (NKILA) after ICH and examined its respective effects on the endoplasmic reticulum stress (ERS)/autophagy pathway, hippocampal neuron loss, and the NF‐kB pathway after type VII collagenase‐induced ICH in rats. The regulatory mechanisms of NKILA were investigated by an intraperitoneal injection of small interfering (siRNA) against NKILA into rats after ICH. NKILA inhibition mediated by siRNA against NKILA was shown to significantly reduce ERS and autophagy, activate the NF‐kB pathway, decrease neurological deficits, brain edema, and injury, and induce blood–brain barrier breakdown, further leading to hippocampal neuron loss and the production of inflammation cytokines. Taken together, the demonstration that NKILA induces the ERS/autophagy pathway and inhibits the NF‐kB pathway after ICH supports the concept that NKILA functions as a novel target that is required for the attenuation of brain injuries after ICH. [ABSTRACT FROM AUTHOR]

Stroke causes death or long-term disabilities and threatens the general health of the population worldwide. Recent studies have suggested that miRNAs are dysregulated and can be used as biomarkers for diagnosis and prognosis in stroke. The intracerebral hemorrhage (ICH) accounts for 15% of all the stroke cases. However, at present, little is known regarding the functions and clinical implications of miRNAs in ICH. In the present study, we established the collagenase-induced rat ICH model to mimic human ICH syndrome. We profiled the expression of 728 rat miRNAs at different time points in rat brain tissues and plasma post-ICH and identified a set human brain-enriched miRNAs that had changed expression level in the plasma of rat ICH. Among them, the expression levels of miR-124 displayed significantly synchronous alterations in rat plasma and brain tissue during ICH progression. They were significantly elevated at the acute injury phase (day 1 and 2), gradually decreased during the delayed recovery phase (day 7, 14 and 30), and finally restored to normal levels at late recovery phase (day 60). We further determined the plasma expression profile of miR-124 from human ICH patients. Similar to the pattern observed in rat ICH model, our results indicated that immediately after patients reached the hospital, the average plasma concentrations of miR-124 increased more than 100-fold in 24 h, then decreased gradually on day 2, 7, 14 and to near normal level on day 30. Taken together, these results strongly suggested that plasma concentration of miR-124 is a promising candidate biomarker for the early detection and predictive prognosis of human ICH. [ABSTRACT FROM AUTHOR]

Background: The neuroprotective effects of neuroserpin (NSP) have been well documented in both patients and animal models with cerebral ischemia; however, have never been investigated in hemorrhagic stroke. The aim of this study is to verify the neuroprotection of NSP in the non-tPA-induced intracerebral hemorrhage (ICH) mouse model.Methods: C57BL/6J male mice (n = 198) were involved in this study. ICH models were established with infusion of autologous blood into the brain parenchyma. We then detected NSP expression in ICH brains by morphological methods and western blotting analysis. We measured the brain water content and detected blood-brain barrier (BBB) permeability to verify the neuroprotective effects of NSP.Results: We found that NSP protein expression was upregulated in ICH models, with a peak at 48 h after ICH induction. NSP local administration reduced the brain edema and the BBB permeability in ICH models. The neurological deficits were also ameliorated. Thus, the neuroprotection of NSP in ICH state was confirmed. Additionally, we also found that the distribution pattern of occludin-expressing cells was obviously changed by the ICH procedure but partly recovered after NSP administration. This finding indicated that protecting and/or repairing the injured vascular endothelial cells may be a potential mechanism involved in NSP neuroprotection, which needs further verification.Conclusions: Our results supported the fact that NSP may be considered as a potential therapy for ICH for the neuroprotective effects including amelioration of the edema. [ABSTRACT FROM AUTHOR]

Somatostatin which is a multifunctional growth hormone inhibitory neuropeptide shows diverse physiological effects, such as neurotransmission, cell growth, apoptosis, and endocrine signaling as well as exerts inhibitory effects on hormonal products and other secretory proteins. SSTR3 is a member of superfamily of somatostatin receptors (SSTR), which are G-protein-coupled plasma membrane receptors. Previous studies proved that SSTR3 regulates antiproliferative signaling and apoptosis in several cells. Here, we explored a potential role of SSTR3 in the regulation of neuronal apoptosis in the course of intracerebral hemorrhage (ICH). An ICH rat model was established and assessed by behavioral tests. We found SSTR3 was significantly upregulated surrounding the hematoma after ICH by Western blot and immunohistochemistry. Double immunofluorescence-manifested SSTR3 was strikingly increased in neurons, not astrocytes or microglia. Moreover, increasing SSTR3 level was found to be accompanied by the upregulation of p53, Bax, and active caspase-3 in vivo and in vitro studies. Furthermore, we detected that neuronal apoptosis marker active caspase-3 was co-localized with SSTR3 suggesting its potential role in neuronal apoptosis. In addition, in vitro study, revealed that SSTR3 knockdown specifically resulted in reducing neuronal apoptosis in PC12 cells, which further indicated that SSTR3 might exert its pro-apoptotic function on neuronal apoptosis. All our findings suggested that upregulated SSTR3 may be involved in neuronal apoptosis after ICH. [ABSTRACT FROM AUTHOR]

Introduction: To analyze whether the computed tomography angiography (CTA) spot sign predicts the intraprocedural rupture rate and outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Methods: From a prospective nationwide multicenter registry database, 1023 patients with aneurysmal subarachnoid hemorrhage (aSAH) were analyzed retrospectively. Descriptive statistics and logistic regression analysis were used to compare spot sign-positive and -negative patients with aneurysmal intracerebral hemorrhage (aICH) for baseline characteristics, aneurysmal and ICH imaging characteristics, treatment and admission status as well as outcome at discharge and 1-year follow-up (1YFU) using the modified Rankin Scale (mRS). Results: A total of 218 out of 1023 aSAH patients (21%) presented with aICH including 23/218 (11%) patients with spot sign. Baseline characteristics were comparable between spot sign-positive and -negative patients. There was a higher clip-to-coil ratio in patients with than without aICH (both spot sign positive and negative). Median aICH volume was significantly higher in the spot sign-positive group (50 ml, 13-223 ml) than in the spot sign-negative group (18 ml, 1-416; p < 0.0001). Patients with a spot sign-positive aICH thus were three times as likely as those with spot sign-negative aICH to show an intraoperative aneurysm rupture [odds ratio (OR) 3.04, 95% confidence interval (CI) 1.04-8.92, p = 0.046]. Spot sign-positive aICH patients showed a significantly worse mRS at discharge (p = 0.039) than patients with spot sign-negative aICH (median mRS 5 vs. 4). Logistic regression analysis showed that the spot sign was an aICH volume-dependent predictor for outcome. Both spot sign-positive and -negative aICH patients showed comparable rates of hospital death, death at 1YFU and mRS at 1YFU. Conclusion: In this multicenter data analysis, patients with spot sign-positive aICH showed higher aICH volumes and a higher rate of intraprocedural aneurysm rupture, but comparable long-term outcome to spot sign-negative aICH patients. [ABSTRACT FROM AUTHOR]

Hemin plays a key role in mediating secondary neuronal injury after intracerebral hemorrhage (ICH) and the cell toxicity of hemin is thought to be due to iron that is liberated when hemin is degraded. In a recent study, we demonstrated the iron regulatory hormone hepcidin reduces brain iron in iron-overloaded rats. Therefore, we hypothesized that hepcidin might be able to reduce iron and then protect neurons from hemin or iron-mediated neurotoxicity in hemin-treated neuronal cells. Here, we tested the hypothesis and demonstrated that ad-hepcidin and hepcidin peptide both have the ability to suppress the hemin-induced increase in LDH release and apoptotic cell numbers, to reduce cell iron and ferritin contents, and to inhibit expression of transferrin receptor 1, divalent metal transporter 1, and ferroportin 1 in hemin-treated neurons. We conclude that hepcidin protects neuron from hemin-mediated injury by reducing iron via inhibition of expression of iron transport proteins. [ABSTRACT FROM AUTHOR]

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Kpnb1, also known as Importin β1, is a member of the Karyopherin protein family which plays a important role in nuclear import and export pathways. Its expression has been shown to be responsive to stress, such as heat shock, ethanol and oxidative stress. Previous studies demonstrated that Kpnb1 had anti-apoptotic in cervical cancer. These together prompted us to explore whether Kpnb1 has some association with neuron apoptosis in the pathophysiology of intracerebral hemorrhage (ICH). In our study, an ICH model was established by injecting into the right basal ganglia of adult rats with their autologous whole blood and assessed by behavioral tests. We found Kpnb1 were significantly up-regulated adjacent to the hematoma following ICH by Western blot and immunohistochemistry. Double immunofluorenscence manifested Kpnb1 was strikingly increased in neurons, not astrocytes or microglia. Furthermore, we also found that kpnb1 had co-localizations with active-caspase-3 which is a neuronal apoptosis marker suggesting its role in neuronal apoptosis. What's more, our in vitro study, using Kpnb1 RNA interference in PC12 cells, further indicated that Kpnb1 might exert its pro-apoptotic function on neuronal apoptosis. Therefore, Kpnb1 may play a role in the neuronal apoptosis following ICH. [ABSTRACT FROM AUTHOR]

Vascular cell adhesion molecule 1 (VCAM1) is a member of the Immunoglobulin superfamily and encodes a cell surface sialoglycoprotein expressed in cytokine-activated endothelium. This type I membrane protein mediates leukocyte-endothelial cell adhesion, facilitates the downstream signaling, and may play a role in the development of artherosclerosis and rheumatoid arthritis. Accumulating evidence has demonstrated that VCAM1 exerts an anti-apoptotic effect in several tumor tissues such as ovarian cancer and breast cancer. Intracerebral hemorrhage (ICH) is the second most common subtype of stroke with high morbidity and mortality, which imposes a big burden on individuals and the whole society. These together prompted us to question whether VCAM1 has some association with neuron apoptosis during the pathological process of ICH. An ICH rat model was established and assessed by behavioral tests in order to explore the role of VCAM1 after ICH. Up-regulation of VCAM1 was observed in brain areas surrounding the hematoma following ICH by western blotting and immunohistochemistry. Immunofluorescence manifested VCAM1 was strikingly increased in neurons, but not in astrocytes and microglia. Furthermore, we detected that neuronal apoptosis marker active caspase-3 had co-localizations with VCAM1. At the same time, Bcl-2 was also co-localized with VCAM1. Taken together, our findings suggested that VCAM1 might be involved in the neuronal apoptosis and pathophysiology of ICH. [ABSTRACT FROM AUTHOR]

Biomedical magnetic induction measurement is a promising method for the detection of intracerebral hemorrhage (ICH), especially in China. Aiming at overcoming the problem of low sensitivity, a magnetic induction sensor is chosen to replace the conventional sensors. It uses a two-arm Archimedean spiral coil as the exciter and a circular coil as the receiver. In order to carry out high-fidelity simulations, the Chinese head model with real anatomical structure is introduced into this novel sensor for the first time. Simulations have been carried out upon early stage ICH measurements. By calculating the state sensitivity and time sensitivity of the perturbation phase of two types of sensors using the electromagnetic software, we conclude that the primary signal received can be largely reduced using the novel sensor, which could effectively increase the time and state sensitivity simultaneously. [ABSTRACT FROM AUTHOR]

Bnip3L, also known as NIX, is a homolog of the E1B 19K/Bcl-2 binding and pro-apoptotic protein Bnip3 which can bind to Bcl-2 to elaborate that effect. In tumor cells, Bnip3L played a role in tumor growth inhibition, but some studies argued hypoxia-induced autophagy via Bnip3L was a survival mechanism that promoted tumor progression. In heart muscle, it related to decreased myocardial function. However, its function in intracerebral hemorrhage (ICH) is still not clear. In this frame, we found the Bnip3L expression increased in the perihematomal region in adult rats after performed ICH. Double immunofluorenscence staining manifested that Bnip3L co-located with neurons, not astrocytes or oligodendrocytes. Furthermore, we detected that neuronal apoptosis marker active caspase-3 had colocalizations with Bnip3L. In addition, colocalizations and co-immunoprecipitation between Bnip3L and Bcl-2, consistent with previous study, were also found. All our findings suggested that Bnip3L might be involved in the pathophysiology of ICH. [ABSTRACT FROM AUTHOR]

Ethnicity and socioeconomic factors can influence disease susceptibility, clinical presentation, and outcome. We investigated the clinical characteristics (age, sex, seasonal variation, lesion site, symptoms, complications, prognosis, and sequelae) and risk factors for intracerebral hemorrhage (ICH) in 266 cases treated at our hospital in Hangzhou City, China, from January 2011 to December 2011. Risk of ICH increased dramatically with age; only 4.3% of cases were <30 years old, while 44.4% were >60 years of age. Men outnumbered women by 2:1 (67.3% vs. 32.7%). Single hemorrhage was most often located in the cerebral lobes (37.2% of cases), basal ganglia (34.2%), thalamus (8.3%), cerebellum (6.8%), ventricle (1.5%), and brainstem (1.1%), while 10.9% of cases exhibited hemorrhages at multiple sites. Hypertension was also a major risk factor for ICH, as 47% of all patients were hypertensive and the percentage increased with age. In hypertensive patients, the most common hemorrhage site was the basal ganglia and ICH was often associated with thrombopenia. In patients with leukemia (all forms), most hemorrhages were lobar. Warfarin- and encephalic operation-associated ICHs were all lobar. Headache was the major symptom of occipital, temporal, and frontal lobe hemorrhage. Dizziness, nausea, and vomiting were the major symptoms of cerebellum hemorrhage. Limb dysfunction was the major symptom of thalamic and basal ganglia hemorrhage. Disturbed level of consciousness was the major symptom in multisite, ventricular, parietal lobe, and brainstem hemorrhage. Hyperspasmia occurred most often in lobar hemorrhage and blurred vision in occipital lobe hemorrhage. Hospital mortality was 24.4% ( n=65) with a mean delay from presentation to death of (10.5±18.5) d. The majority of fatalities were cerebral hernia cases (58.5%) and these patients also had the shortest time to death [(2.9±3.5) d]. Mortality was 100% in brainstem ICH and hemorrhagic conversion of cerebral infarct. Thrombopenia-associated ICH also had a high mortality rate (81.0%), while patients with cerebrovascular malformations and cerebral aneurysms demonstrated a much better prognosis (46.2% recovery). [ABSTRACT FROM AUTHOR]

Background: Heme oxygenase-1 (HO-1), the rate-limiting enzyme for heme catabolism and iron production, its role in intracerebral hemorrhage (ICH) is controversial. The study was to investigate correlations between brain oxidative injury and HO-1 after experimental ICH. Method: Sprague-Dawley rats received intra-striatal infusions of 100 μl autologous whole blood as ICH models. HO-1 were examined by immunohistochemical and reverse transcription polymerase chain reaction (RT-PCR) analysis. Brain oxidative stress was quantitated by malondialdehyde (MDA); antioxidation were measured by copper-zinc superoxide dismutase (Cu/Zn-SOD) activity using RT-PCR assay. Results: The expression of the HO-1 upregulated and reached its peak at days 3 and 7 after ICH ( P < 0.01). There was a significant increase of MDA and a top at 3-day post-ICH ( P < 0.01); Cu/Zn-SOD was upregulated post-ICH and reached the top at day 7 ( P < 0.001); HO-1 was correlated significantly with brain MDA content at days 7 and 14 following ICH ( r = 0.435-0.501, P < 0.001) but there is no definite correlation between them on 1 to 3 days ( P > 0.05); conversely, HO-1 was correlated significantly with Cu/Zn-SOD on 1 to 3 days after ICH ( r = 0.433-0.621, P < 0.001) but there is no definite correlation between them at days 7 and 14 ( P > 0.05). Conclusions: HO-1 has both antioxidant and prooxidant properties in ICH. The early upregulation of HO-1 possibly fit with the events and be protective against oxidative stress, whereas its overexpression in the late stages may result in its dysfunction and be toxic. So it should be prudent to intervene ICH with the inhibitor/activator of HO-1. [ABSTRACT FROM AUTHOR]

In the present study, we investigated whether the administration of nicotinamide adenine dinucleotide (NAD+) provides brain protection in a mouse model of intracerebral hemorrhage (ICH). Male CD-1 mice were divided into sham, ICH treated with vehicle and ICH treated with NAD+ (10 or 20 mg/kg, intranasal) groups. Intranasal delivery of NAD+ resulted in an increase in NAD+ contents in the brains. ICH was induced by collagenase injection. Neurological function, hemorrhage volume and brain edema were measured 24 hours after injection. ICH caused significant neurological deficit with associated brain edema. NAD+ (10 and 20 mg/kg) failed to reduce brain injury after ICH. These results suggest that NAD+ has no neuroprotective effect at 24 hours after ICH. [ABSTRACT FROM AUTHOR]

We studied how well the original intracerebral hemorrhage (ICH) score would predict mortality. All nine patients with an ICH score of 0 survived, whereas those having scores of 1, 2, 3, and 4 had 10, 53, 71, and 100 % mortality, respectively. Thirty-nine patients were found to have hematoma of <30 mL (56 % survived), whereas 11 patients were found to have volume of >30 mL (only 10 % survived). The ICH score and volume is a simple clinical grading scale that allows risk stratification on presentation with ICH. The use of a scale such as the ICH score could improve standardization of clinical treatment protocols. [ABSTRACT FROM AUTHOR]

Given the ongoing global SARS-CoV-2-vaccination efforts, clinical awareness needs to be raised regarding the possibility of an increased incidence of SARS-CoV-2-vaccine-related immune-mediated thrombocytopenia in patients with intracerebral hemorrhage (ICH) secondary to cerebral sinus and vein thrombosis (CVT) requiring (emergency) neurosurgical treatment in the context of vaccine-induced immune thrombotic thrombocytopenia (VITT). Only recently, an association of vaccinations and cerebral sinus and vein thrombosis has been described. In a number of cases, neurosurgical treatment is warranted for these patients and special considerations are warranted when addressing the perioperative coagulation. We, herein, describe the past management of patients with VITT and established a literature-guided algorithm for the treatment of patients when addressing the impaired coagulation in these patients. Increasing insights addressing the pathophysiology of SARS-CoV-2-vaccine-related immune-mediated thrombocytopenia guide physicians in developing an interdisciplinary algorithm taking into account the special considerations of this disease. [ABSTRACT FROM AUTHOR]

Hypertension (HTN) is the most common cause of non-traumatic ICH, yet echocardiography, which can stage hypertensive heart disease (HHD), is not part of the routine evaluation of patients with ICH. Previous studies have shown that angiotensin converting enzyme inhibitors and angiotensin receptor blockers are associated with regression of left ventricular hypertrophy (LVH) and reversal of myocardial fibrosis. Improvement in these architectural changes in the heart has been shown to improve outcomes and prevent major adverse cardiac events, including stroke. Obtaining echocardiography on ICH patients routinely could help to access the prevalence of HHD and to tailor antihypertensive regimens in this high risk group of patients. Further study is required to determine whether angiotensin directed therapies provide optimal secondary prevention in ICH patients with HHD. [ABSTRACT FROM AUTHOR]