The clinical value of nutritional and inflammatory indicators in predicting pneumonia among patients with intracerebral hemorrhage.

Immunosuppression and malnutrition play pivotal roles in the complications of intracerebral hemorrhage (ICH) and are intricately linked to the development of stroke-associated pneumonia (SAP). Inflammatory markers, including NLR (neutrophil-to-lymphocyte ratio), SII (systemic immune inflammation index), SIRI (systemic inflammatory response index), and SIS (systemic inflammation score), along with nutritional indexes such as CONUT (controlling nutritional status) and PNI (prognostic nutritional index), are crucial indicators influencing the inflammatory state following ICH. In this study, our objective was to compare the predictive efficacy of inflammatory and nutritional indices for SAP in ICH patients, aiming to determine and explore their clinical utility in early pneumonia detection. Patients with severe ICH requiring ICU admission were screened from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The outcomes included the occurrence of SAP and in-hospital death. Receiver operating characteristic (ROC) analysis, multivariate logistic regression, smooth curve analysis, and stratified analysis were employed to investigate the relationship between the CONUT index and the clinical outcomes of patients with severe ICH. A total of 348 patients were enrolled in the study. The incidence of SAP was 21.3%, and the in-hospital mortality rate was 17.0%. Among these indicators, multiple regression analysis revealed that CONUT, PNI, and SIRI were independently associated with SAP. Further ROC curve analysis demonstrated that CONUT (AUC 0.6743, 95% CI 0.6079-0.7408) exhibited the most robust predictive ability for SAP in patients with ICH. Threshold analysis revealed that when CONUT < 6, an increase of 1 point in CONUT was associated with a 1.39 times higher risk of SAP. Similarly, our findings indicate that CONUT has the potential to predict the prognosis of patients with ICH. Among the inflammatory and nutritional markers, CONUT stands out as the most reliable predictor of SAP in patients with ICH. Additionally, it proves to be a valuable indicator for assessing the prognosis of patients with ICH.

Low Prognostic Nutritional Index Predicts In-Hospital Complications and Case Fatality in Patients with Spontaneous Intracerebral Hemorrhage: A Retrospective Study.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is associated with high case fatality and significant healthcare costs. Recent studies emphasize the critical role of nutritional status in affecting outcomes in neurological disorders. This study investigates the relationship between the Prognostic Nutrition Index (PNI) and in-hospital complications and case fatality among patients with ICH. METHODS: A retrospective analysis was performed using data from the Changhua Christian Hospital Clinical Research Database between January 2015 and December 2022. Patients under 20 or over 100 years of age or with incomplete medical data were excluded. We utilized restricted cubic spline models, Kaplan-Meier survival analysis, and ROC analysis to assess the association between PNI and clinical outcomes. Propensity score matching analysis was performed to balance these clinical variables between groups. RESULTS: In this study, 2402 patients with spontaneous ICH were assessed using the median PNI value of 42.77. The cohort was evenly divided between low and high PNI groups, predominantly male (59.1%), with an average age of 64 years. Patients with lower PNI scores at admission had higher in-hospital complications and increased 28- and 90-day case fatality rates. CONCLUSIONS: Our study suggests that PNI could serve as a valuable marker for predicting medical complications and case fatality in patients with spontaneous ICH.

Necrotizing enterocolitis in a term newborn after spontaneous cerebral parenchymal hemorrhage: a case report.

BACKGROUND: Necrotizing enterocolitis (NEC) and intracranial hemorrhage are severe emergencies in the neonatal period. The two do not appear to be correlated. However, our report suggests that parenchymal brain hemorrhage in full-term newborns may put patients at risk for NEC by altering intestinal function through the brain-gut axis. CASE PRESENTATION: We present a case of spontaneous parenchymal cerebral hemorrhage in a full-term newborn who developed early-stage NEC on Day 15. CONCLUSIONS: It is possible to consider brain parenchymal hemorrhage as a risk factor for the appearance of NEC. Clinicians should be highly cautious about NEC in infants who have experienced parenchymal hemorrhage. This article is the first to discuss the relationship between parenchymal hemorrhage and NEC in full-term newborns.

HE-Mind: A model for automatically predicting hematoma expansion after spontaneous intracerebral hemorrhage.

PURPOSE: To develop and validate an end-to-end model for automatically predicting hematoma expansion (HE) after spontaneous intracerebral hemorrhage (sICH) using a novel deep learning framework. METHODS: This multicenter retrospective study collected cranial noncontrast computed tomography (NCCT) images of 490 patients with sICH at admission for model training (n = 236), internal testing (n = 60), and external testing (n = 194). A HE-Mind model was designed to predict HE, which consists of a densely connected U-net for segmentation process, a multi-instance learning strategy for resolving label ambiguity and a Siamese network for classification process. Two radiomics models based on support vector machine or logistic regression and two deep learning models based on residual network or Swin transformer were developed for performance comparison. Reader experiments including physician diagnosis mode and artificial intelligence mode were conducted for efficiency comparison. RESULTS: The HE-Mind model showed better performance compared to the comparative models in predicting HE, with areas under the curve of 0.849 and 0.809 in the internal and external test sets respectively. With the assistance of the HE-Mind model, the predictive accuracy and work efficiency of the emergency physician, junior radiologist, and senior radiologist were significantly improved, with accuracies of 0.768, 0.789, and 0.809 respectively, and reporting times of 7.26 s, 5.08 s, and 3.99 s respectively. CONCLUSIONS: The HE-Mind model could rapidly and automatically process the NCCT data and predict HE after sICH within three seconds, indicating its potential to assist physicians in the clinical diagnosis workflow of HE.

Peripheral cytokine interleukin-10 alleviates perihematomal edema after intracerebral hemorrhage via interleukin-10 receptor/JAK1/STAT3 signaling.

AIMS: The extent of perihematomal edema following intracerebral hemorrhage (ICH) significantly impacts patient prognosis, and disruption of the blood-brain barrier (BBB) exacerbates perihematomal edema. However, the role of peripheral IL-10 in mitigating BBB disruption through pathways that link peripheral and central nervous system signals remains poorly understood. METHODS: Recombinant IL-10 was administered to ICH model mice via caudal vein injection, an IL-10-inhibiting adeno-associated virus and an IL-10 receptor knockout plasmid were delivered intraventricularly, and neurobehavioral deficits, perihematomal edema, BBB disruption, and the expression of JAK1 and STAT3 were evaluated. RESULTS: Our study demonstrated that the peripheral cytokine IL-10 mitigated BBB breakdown, perihematomal edema, and neurobehavioral deficits after ICH and that IL-10 deficiency reversed these effects, likely through the IL-10R/JAK1/STAT3 signaling pathway. CONCLUSIONS: Peripheral IL-10 has the potential to reduce BBB damage and perihematomal edema following ICH and improve patient prognosis.

Machine learning-based model for predicting outcomes in cerebral hemorrhage patients with leukemia.

BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) in leukemia patients progresses rapidly with high mortality. Limited data are available on imaging studies in this population. The study aims to develop prediction models for 7-day and short-term mortality risk based on the non-contrast computed tomography (NCCT) image features. METHODS: The NCCT image features of ICH in 135 leukemia patients between 2007-2023 were retrospectively extracted using manual assessment and radiomics methods. After multiple imputation of missing laboratory data, univariate logistic regression and least absolute shrinkage and selection operator (LASSO) were used for feature selection. Random forest models were built with comprehensive evaluation and ranking of feature importance. RESULT: 135 and 129 patients were included in the studies for 7-day and short-term prognostic models, respectively. The median age of all enrolled patients was 35 years, and there were 86 male patients (63.7 %). Clinical models (validation: AUC [area under the curve] = 0.78, AUPRC [area under the precision-recall curve] = 0.73; AUC = 0.84, AUPRC = 0.86), radiomics models (validation: AUC = 0.82, AUPRC = 0.78; AUC = 0.75, AUPRC = 0.77), and the combined models (validation: AUC = 0.84, AUPRC = 0.83; AUC = 0.87, AUPRC = 0.89) predicted 7-day and short-term mortality with good predictive efficacy. Clinical decision curve analysis showed that the combined models predicted 7-day and 30-day risk of death would be more beneficial than other models. Shape features contributed significantly more than semantic features in both radiomics models and combined models (93.3 %, 52.1 %, as well as 85.2 %,37.4 %, respectively) for 7-day and 30-day mortality. CONCLUSIONS: Combined models constructed based on NCCT perform well in predicting the risk of 7-day and short-term mortality in ICH patients with leukemia. Shape features extracted by radiomics are important markers for modeling the prognosis.

Swirl sign score system: a novel and practical tool for predicting hematoma expansion risk after spontaneous intracerebral haemorrhage.

OBJECTIVE: To methodically analyse the swirl sign and construct a scoring system to predict the risk of hematoma expansion (HE) after spontaneous intracerebral haemorrhage (sICH). METHODS: We analysed 231 of 683 sICH patients with swirl signs on baseline noncontrast CT (NCCT) images. The characteristics of the swirl sign were analysed, including the number, maximum diameter, shape, boundary, minimum CT value of the swirl sign, and the minimum distance from the swirl sign to the edge of the hematoma. In the development cohort, univariate and multivariate analyses were used to identify independent predictors of HE, and logistic regression analysis was used to construct the swirl sign score system. The swirl sign score system was verified in the validation cohort. RESULTS: The number and the minimum CT value of the swirl sign were independent predictors of HE. The swirl sign score system was constructed (2 points for the number of swirl signs >1 and 1 point for the minimum CT value ≤41 Hounsfield units). The area under the curve of the swirl sign score system in predicting HE was 0.773 and 0.770 in the development and validation groups, respectively. CONCLUSIONS: The swirl sign score system is an easy-to-use radiological grading scale that requires only baseline NCCT images to effectively identify subjects at high risk of HE. ADVANCES IN KNOWLEDGE: Our newly developed semiquantitative swirl sign score system greatly improves the ability of swirl sign to predict HE.

Outcome Trajectories after Intracerebral Hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) is the most morbid of all stroke types with a high early mortality and significant early disability burden. Traditionally, outcome assessments after ICH have mirrored those of acute ischemic stroke, with 3 months post-ICH being considered a standard time point in most clinical trials, observational studies, and clinical practice. At this time point, the majority of ICH survivors remain with moderate to severe functional disability. However, emerging data suggest that recovery after ICH occurs over a more protracted course and requires longer periods of follow-up, with more than 40% of ICH survivors with initial severe disability improving to partial or complete functional independence over 1 year. Multiple other domains of recovery impact ICH survivors including cognition, mood, and health-related quality of life, all of which remain under studied in ICH. To further complicate the picture, the most important driver of mortality after ICH is early withdrawal of life-sustaining therapies, before initiation of treatment and evaluating effects of prolonged supportive care, influenced by early pessimistic prognostication based on baseline severity factors and prognostication biases. Thus, our understanding of the true natural history of ICH recovery remains limited. This review summarizes the existing literature on outcome trajectories in functional and nonfunctional domains, describes limitations in current prognostication practices, and highlights areas of uncertainty that warrant further research.

Abnormal dynamic functional connectivity in young nondisabling intracerebral hemorrhage patients.

OBJECTIVE: Previous resting-state functional magnetic resonance imaging studies on intracerebral hemorrhage patients have focused more on the static characteristics of brain activity, while the time-varying effects during scanning have received less attention. Therefore, the current study aimed to explore the dynamic functional network connectivity changes of intracerebral hemorrhage patients. METHODS: Using independent component analysis, the sliding window approach, and the k-means clustering analysis method, different dynamic functional network connectivity states were detected from resting-state functional magnetic resonance imaging data of 37 intracerebral hemorrhage patients and 44 healthy controls. The inter-group differences in dynamic functional network connectivity patterns and temporal properties were investigated, followed by correlation analyses between clinical scales and abnormal functional indexes. RESULTS: Ten resting-state networks were identified, and the dynamic functional network connectivity matrices were clustered into four different states. The transition numbers were decreased in the intracerebral hemorrhage patients compared with healthy controls, which was associated with trail making test scores in patients. The cerebellar network and executive control network connectivity in State 1 was reduced in patients, and this abnormal dynamic functional connectivity was positively correlated with the animal fluency test scores of patients. INTERPRETATION: The current study demonstrated the characteristics of dynamic functional network connectivity in intracerebral hemorrhage patients and revealed that abnormal temporal properties and functional connectivity may be related to the performance of different cognitive domains after ictus. These results may provide new insights into exploring the neurocognitive mechanisms of intracerebral hemorrhage.

[Extremely preterm infants with severe intraventricular hemorrhage: neurological evolution and long term and educational status]. / Niños muy prematuros con hemorragia intraventricular extensa: evolución neurológica y escolaridad a largo plazo.

Extensive intraventricular hemorrhage (IVH) in very preterm newborns (VPNB) is associated with mortality and severe long-term neurological sequelae. OBJECTIVES: To know the most frequent neurological pathologies associated with extensive IVH, to determine the functional outcomes of mobility in the motor area and intellectual capacity in the cognitive area, to analyze the association between both areas and to know the schooling achieved. PATIENTS AND METHOD: Descriptive and longitudinal study in VPNB with extensive IVH born between 2001 and 2014. They underwent protocolized neurological follow-up until school age. The functional outcomes in mobility and intellectual capacity were categorized into 4 levels: level 1 corresponds to good functionality and autonomy; level 2, functionality that allows independence, with support in some tasks; level 3 requires constant external support; and level 4 where there is total dependence. The association was analyzed using Chi-square and Cramer's V coefficient. RESULTS: 74 children completed the follow-up; the most frequent associated neurological pathologies were neurodevelopmental disorders, hypertensive hydrocephalus, and epilepsy. Independent mobility (normal or with limitations) reached 74.4% while 24.3% used wheelchairs. 51.3% was categorized as normal to borderline intellectual range, 12.2% as mild intellectual disability (ID), 17.6% as moderate ID, and 19.9% as severe to profound ID. There was a strong statistical association between functional levels of mobility and intellectual capacity (p < 0.000 and V = 0.62). Schooling was proportional to intellectual capacity: 56.8% attended regular schools, 27.0% attended special schools, and 16.2% had no schooling. CONCLUSIONS: 2/3 VPNB with extensive IVH showed positive functional outcomes, from normal to mild limitations that allow an almost autonomous life; in 1/3 the outcomes were unfavorable in mobility and cognitive performance, and there was a strong statistical correlation between both areas studied. Schooling was consistent with the intellectual level.

Using 30-day modified rankin scale score to predict 90-day score in patients with intracranial hemorrhage: Derivation and validation of prediction model.

Whether 30-day modified Rankin Scale (mRS) scores can predict 90-day scores is unclear. This study derived and validated a model to predict ordinal 90-day mRS score in an intracerebral hemorrhage (ICH) population using 30-day mRS values and routinely available baseline variables. Adults enrolled in the Antihypertensive Treatment of Acute Cerebral Hemorrhage-2 (ATACH-2) trial between May 2011 and September 2015 with acute ICH, who were alive at 30 days and had mRS scores reported at both 30 and 90 days were included in this post-hoc analysis. A proportional odds regression model for predicting ordinal 90-day mRS scores was developed and internally validated using bootstrapping. Variables in the model included: mRS score at 30 days, age (years), hematoma volume (cm3), hematoma location (deep [basal ganglia, thalamus], lobar, or infratentorial), presence of intraventricular hemorrhage (IVH), baseline Glasgow Coma Scale (GCS) score, and National Institutes of Health Stroke Scale (NIHSS) score at randomization. We assessed model fit, calibration, discrimination, and agreement (ordinal, dichotomized functional independence), and EuroQol-5D ([EQ-5D] utility weighted) between predicted and observed 90-day mRS. A total of 898/1000 participants were included. Following bootstrap internal validation, our model (calibration slope = 0.967) had an optimism-corrected c-index of 0.884 (95% CI = 0.873-0.896) and R2 = 0.712 for 90-day mRS score. The weighted ĸ for agreement between observed and predicted ordinal 90-day mRS score was 0.811 (95% CI = 0.787-0.834). Agreement between observed and predicted functional independence (mRS score of 0-2) at 90 days was 74.3% (95% CI = 69.9-78.7%). The mean ± SD absolute difference between predicted and observed EQ-5D-weighted mRS score was negligible (0.005 ± 0.145). This tool allows practitioners and researchers to utilize clinically available information along with the mRS score 30 days after ICH to reliably predict the mRS score at 90 days.

Blood Pressure Management in Intracerebral Haemorrhage: when, how much, and for how long?

PURPOSE OF REVIEW: When compared to ischaemic stroke, there have been limited advances in acute management of intracerebral haemorrhage. Blood pressure control in the acute period is an intervention commonly implemented and recommended in guidelines, as elevated systolic blood pressure is common and associated with haematoma expansion, poor functional outcomes, and mortality. This review addresses the uncertainty around the optimal blood pressure intervention, specifically timing and length of intervention, intensity of blood pressure reduction and agent used. RECENT FINDINGS: Recent pivotal trials have shown that acute blood pressure intervention, to a systolic target of 140mmHg, does appear to be beneficial in ICH, particularly when bundled with other therapies such as neurosurgery in selected cases, access to critical care units, blood glucose control, temperature management and reversal of coagulopathy. Systolic blood pressure should be lowered acutely in intracerebral haemorrhage to a target of approximately 140mmHg, and that this intervention is generally safe in the ICH population.

Peroxiredoxin II exerts neuroprotective effects by inhibiting endoplasmic reticulum stress and oxidative stress-induced neuronal pyroptosis.

BACKGROUND: Intracerebral hemorrhage (ICH) is a critical neurological condition with few treatment options, where secondary immune responses and specific cell death forms, like pyroptosis, worsen brain damage. Pyroptosis involves gasdermin-mediated membrane pores, increasing inflammation and neural harm, with the NLRP3/Caspase-1/GSDMD pathway being central to this process. Peroxiredoxin II (Prx II), recognized for its mitochondrial protection and reactive oxygen species (ROS) scavenging abilities, appears as a promising neuronal pyroptosis modulator. However, its exact role and action mechanisms need clearer definition. This research aims to explore Prx II impact on neuronal pyroptosis and elucidate its mechanisms, especially regarding endoplasmic reticulum (ER) stress and oxidative stress-induced neuronal damage modulation. METHODS AND RESULTS: Utilizing MTT assays, Microscopy, Hoechst/PI staining, Western blotting, and immunofluorescence, we found Prx II effectively reduces LPS/ATP-induced pyroptosis and neuroinflammation in HT22 hippocampal neuronal cells. Our results indicate Prx II's neuroprotective actions are mediated through PI3K/AKT activation and ER stress pathway inhibition, diminishing mitochondrial dysfunction and decreasing neuronal pyroptosis through the ROS/MAPK/NF-κB pathway. These findings highlight Prx II potential therapeutic value in improving intracerebral hemorrhage outcomes by lessening secondary brain injury via critical signaling pathway modulation involved in neuronal pyroptosis. CONCLUSIONS: Our study not only underlines Prx II importance in neuroprotection but also opens new therapeutic intervention avenues in intracerebral hemorrhage, stressing the complex interplay between redox regulation, ER stress, and mitochondrial dynamics in neuroinflammation and cell death management.

Paroxysmal sympathetic hyperexcitability after brain injury: A clinical analysis of case series.

BACKGROUND: Paroxysmal sympathetic hyperexcitability (PSH) is a group of complex syndromes with various etiologies. Previous studies were limited to the description of traumatic brain injury (TBI), and the description of PSH after other types of brain injury was rare. We explored the clinical features, treatment, and prognosis of PSH after various types of brain injuries. METHODS: Patients admitted to the neurosurgery intensive care unit with PSH after brain injury from July 2019 to December 2022 were included. Demographic data, clinical manifestations, drug therapy, and disease prognosis were retrospectively collected and analyzed. RESULTS: Fifteen male and 9 female patients with PSH after brain injury were selected. TBI was most likely to cause PSH (66.7%), followed by spontaneous intracerebral hemorrhage (25%). Glasgow coma scale scores of 19 patients (79.2%) were lower than 8 and 14 patients (58.3%) underwent tracheotomy. Electroencephalogram monitoring was performed in 12 individuals, none of which showed epileptic waves. Clinical symptom scale showed mild symptoms in 17 cases (70.8%). Almost all patients were administered a combination of drugs. After follow-up, most patients had a poor prognosis and 2 (8.3%) died after discharge. CONCLUSION: The etiology of PSH is complex. TBI may be the most common cause of PSH. Non-TBI may also be an important cause of PSH. Therefore, early identification, prevention and diagnosis are helpful for determining the prognosis and outcome of the disease.

Association of large core middle cerebral artery stroke and hemorrhagic transformation with hospitalization outcomes.

Historically, investigators have not differentiated between patients with and without hemorrhagic transformation (HT) in large core ischemic stroke at risk for life-threatening mass effect (LTME) from cerebral edema. Our objective was to determine whether LTME occurs faster in those with HT compared to those without. We conducted a two-center retrospective study of patients with ≥ 1/2 MCA territory infarct between 2006 and 2021. We tested the association of time-to-LTME and HT subtype (parenchymal, petechial) using Cox regression, controlling for age, mean arterial pressure, glucose, tissue plasminogen activator, mechanical thrombectomy, National Institute of Health Stroke Scale, antiplatelets, anticoagulation, temperature, and stroke side. Secondary and exploratory outcomes included mass effect-related death, all-cause death, disposition, and decompressive hemicraniectomy. Of 840 patients, 358 (42.6%) had no HT, 403 (48.0%) patients had petechial HT, and 79 (9.4%) patients had parenchymal HT. LTME occurred in 317 (37.7%) and 100 (11.9%) had mass effect-related deaths. Parenchymal (HR 8.24, 95% CI 5.46-12.42, p < 0.01) and petechial HT (HR 2.47, 95% CI 1.92-3.17, p < 0.01) were significantly associated with time-to-LTME and mass effect-related death. Understanding different risk factors and sequelae of mass effect with and without HT is critical for informed clinical decisions.

Glucose Control and Risk of Symptomatic Intracerebral Hemorrhage Following Thrombolysis for Acute Ischemic Stroke: A SHINE Trial Analysis.

BACKGROUND AND OBJECTIVES: Baseline hyperglycemia is associated with worse outcomes in acute ischemic stroke (AIS), including higher risk of symptomatic intracerebral hemorrhage (sICH) following treatment with thrombolysis. Prospective data are lacking to inform management of post-thrombolysis hyperglycemia. In a prespecified analysis from the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial of hyperglycemic stroke management, we hypothesized that post-thrombolysis hyperglycemia is associated with a higher risk of sICH. METHODS: Hyperglycemic AIS patients <12 hours onset were randomized to intensive insulin (target range 80-130 mg/dL) vs standard sliding scale (80-179 mg/dL) over a 72-hour period, stratified by treatment with thrombolysis. Three board-certified vascular neurologists independently reviewed all sICH events occurring within 7 days, defined by neurologic deterioration of ≥4 points on the NIH Stroke Scale (NIHSS). Associations between blood glucose control and sICH were analyzed using logistic regression accounting for NIHSS, age, systolic blood pressure, onset to thrombolysis time, and endovascular therapy (odds ratios [OR], 95% CI). Additional analysis compared patients in a high-risk group (age older than 60 years and NIHSS ≥8) vs all others. Categorical variables and outcomes were compared using the χ2 test (p < 0.05). RESULTS: Of 1151 SHINE participants, 725 (63%) received thrombolysis (median age 65 years, 46% women, 29% Black, 18% Hispanic). The median NIHSS was 7, baseline blood glucose was 187 (interquartile range 153-247) mg/dL, and 80% were diabetic. Onset to thrombolysis time was 2.2 hours (1.6-2.9). Post-thrombolysis sICH occurred in 3.6% (3.0% intensive vs 4.3% standard glucose control, OR 1.10, 0.60-2.01, p = 0.697). In the first 12 hours, every 10 mg/dL higher glucose increased the odds of sICH (OR 1.08, 1.03-1.14, p = 0.004), and a greater proportion of glucose measures in the normal range (80-130 mg/dL) decreased the odds of sICH (0.89, 0.80-0.99, p = 0.030). These associations were strongest in the high-risk group (age older than 60 years and NIHSS ≥8). DISCUSSION: In this prespecified analysis from the SHINE trial, intensive insulin therapy was not associated with a reduced risk of post-thrombolysis sICH compared with standard sliding scale. However, early post-thrombolysis hyperglycemia was associated with a higher risk of sICH overall, particularly in older patients with more severe strokes. Further prospective research is warranted to address the risk of sICH in hyperglycemic stroke patients undergoing endovascular therapy. TRIAL REGISTRATION INFORMATION: NCT01369069.

Electroacupuncture reduces oxidative stress response and improves secondary injury of intracerebral hemorrhage in rats by activating the peroxisome proliferator-activated receptor-γ/nuclear factor erythroid2-related factor 2/γ-glutamylcysteine synthetase pathway.

Intracerebral hemorrhage (ICH) is a severe stroke subtype. Secondary injury is a key factor leading to neurological deficits after ICH. Electroacupuncture (EA) can improve the neurological function after ICH, however, its internal mechanism is still unclear. The aim of this study is to investigate whether EA could ameliorate secondary injury after ICH through antioxidative stress and its potential regulatory mechanism. A rat model of ICH was established by injecting autologous blood into striatum. After the intervention of EA and EA combined with peroxisome proliferator-activated receptor-γ (PPARγ) blocker, Zea-longa scores, modified neurological severity scores and open field tests were used to evaluate the neurological function of the rats. Flow cytometry detected tissue reactive oxygen species (ROS) levels. Tissue tumor necrosis factor-α (TNF-α) levels were analyzed by enzyme-linked immunosorbent assays. The protein expressions of PPAR γ, nuclear factor erythroid2-related factor 2 (Nrf2) and γ-glutamylcysteine synthetase (γ-GCS) were detected by Western blot. Immunohistochemistry was used to observe the activation of microglia. The demyelination degree of axon myelin was observed by transmission electron microscope. Compared with the model group, EA intervention improved neurological function, decreased ROS and TNF-α levels, increased the protein expression of PPARγ, Nrf2 and γ-GCS, and reduced the activation of microglia, it also alleviated axonal myelin sheath damage. In addition, the neuroprotective effect of EA was partially attenuated by PPARγ blocker. EA ameliorated the neurological function of secondary injury after ICH in rats, possibly by activating the PPARγ/Nrf2/γ-GCS signaling pathway, reducing microglia activation, and inhibiting oxidative stress, thus alleviating the extent of axonal demyelination plays a role.

Neuropsychiatric symptoms with focus on apathy and irritability in sporadic and hereditary cerebral amyloid angiopathy.

BACKGROUND: Neuropsychiatric symptoms (NPS) may affect cognition, but their burden in cerebral amyloid angiopathy (CAA), one of the main causes of intracerebral hemorrhage (ICH) and dementia in the elderly, remains unclear. We investigated NPS, with emphasis on apathy and irritability in sporadic (sCAA) and Dutch-type hereditary (D-)CAA. METHODS: We included patients with sCAA and (pre)symptomatic D-CAA, and controls from four prospective cohort studies. We assessed NPS per group, stratified for history of ICH, using the informant-based Neuropsychiatric Inventory (NPI-Q), Starkstein Apathy scale (SAS), and Irritability Scale. We modeled the association of NPS with disease status, executive function, processing speed, and CAA-burden score on MRI and investigated sex-differences. RESULTS: We included 181 participants: 82 with sCAA (mean[SD] age 72[6] years, 44% women, 28% previous ICH), 56 with D-CAA (52[11] years, 54% women, n = 31[55%] presymptomatic), and 43 controls (69[9] years, 44% women). The NPI-Q NPS-count differed between patients and controls (sCAA-ICH+:adj.ß = 1.4[95%CI:0.6-2.3]; sCAA-ICH-:1.3[0.6-2.0]; symptomatic D-CAA:2.0[1.1-2.9]; presymptomatic D-CAA:1.2[0.1-2.2], control median:0[IQR:0-3]), but not between the different CAA-subgroups. Apathy and irritability were reported most frequently: n = 12[31%] sCAA, 19[37%] D-CAA had a high SAS-score; n = 12[29%] sCAA, 14[27%] D-CAA had a high Irritability Scale score. NPS-count was associated with decreased processing speed (adj.ß=-0.6[95%CI:-0.8;-0.4]) and executive function (adj.ß=-0.4[95%CI:-0.6;-0.1]), but not with radiological CAA-burden. Men had NPS more often than women. DISCUSSION: According to informants, one third to half of patients with CAA have NPS, mostly apathy, even in presymptomatic D-CAA and possibly with increased susceptibility in men. Neurologists should inform patients and caregivers of these disease consequences and treat or refer patients with NPS appropriately.

Loganin exerts neuroprotective effect by inhibiting neuronal pyroptosis in rat with cerebral haemorrhage.

Intracerebral haemorrhage (ICH) presents significant challenges in clinical management because of the high morbidity and mortality, necessitating novel therapeutic approaches. This study aimed to assess the neuroprotective effects of loganin in a rat ICH model. Sprague-Dawley rats were used, subjected to a collagenase-induced ICH model, followed by loganin treatment at doses of 2.5, 5 and 10 mg/kg. Neurological functions were evaluated using the modified neurological severity score (mNSS) and a rotarod test. Results indicated a significant improvement in neurological functions in loganin-treated groups, evident from the mNSS and rotarod tests, suggesting dose-dependent neuroprotection. Loganin also effectively reduced the blood-brain barrier (BBB) permeability and cerebral oedema. Additionally, it mitigated cellular pyroptosis, as shown by terminal deoxynucleotidyl transferase dUTP nick-end labelling staining and western blot analysis, which indicated reduced levels of pyroptosis markers in treated rats. Furthermore, loganin's regulatory effects on the adenosine A2A receptor and myosin light chain kinase pathways were observed, potentially underpinning its protective mechanism against ICH. The study concludes that loganin exhibits significant neuroprotective properties in a rat ICH model, highlighting its potential as a novel therapeutic strategy. Despite promising results, the study needs further research to determine loganin's therapeutic potential in human ICH patients. This research paves the way for further exploration into loganin's clinical applications, potentially revolutionizing treatment strategies for patients suffering from intracerebral haemorrhage.