Search

Objective: To assess the frequency of lymphocyte subsets and other laboratory indicators in paired cerebrospinal fluid (CSF) and peripheral blood (PB) samples from critically ill patients with intracerebral hemorrhage (ICH) who developed systemic inflammatory response syndrome (SIRS) following surgery., Introduction: Neuroinflammation and systemic inflammatory responses significantly contribute to secondary brain injury following ICH. Post-surgery SIRS is known to worsen clinical outcomes in ICH patients; however, the immune response in the CSF and PB has not been fully characterized. Understanding immunological changes in ICH patients with SIRS could lead to improved clinical management and prognostic outcomes., Methods: This study involved a retrospective analysis of data from patients with ICH who underwent surgery in the Neurological Intensive Care Unit (NICU) of Baoding No. 1 Hospital, Hebei Province, China, between January and July 2022. Patients were divided into SIRS and non-SIRS groups based on the clinical criteria. Demographic, clinical, and laboratory data, including lymphocyte subsets in CSF and PB, were collected and analyzed. This study compared lymphocyte subsets and other inflammatory markers between the SIRS and non-SIRS groups., Results: Patients with SIRS demonstrated higher systolic blood pressure (SBP) at admission, worse 90-day prognoses, elevated inflammatory markers, increased levels of complement proteins C3 and C4, and lower levels of immunoglobulin G (IgG) compared to patients without SIRS. Between 3-6 days post-surgery, SIRS patients showed higher percentages of CD3+T cells, CD4+T cells, and CD4+/CD8+ ratios in the CSF than non-SIRS patients. CD3+T cell percentages in the CSF were consistently higher than those in the PB and were independent of PB levels. In contrast, CD3-CD16+CD56+ natural killer (NK) cell percentages were lower in patients with SIRS. No significant differences in PB lymphocyte subsets were found between the two groups. A high CSF CD3+T cell percentage (≥85.68 %) was identified as the strongest predictor of critical ICH with SIRS after surgery, with an appropriate use criterion (AUC) of 0.7742, sensitivity of 77.42 %, specificity of 76.19 %, and 95 % CI of 0.6655-0.8829 (P < 0.0001)., Conclusion: Elevated levels of CD3+T lymphocytes in CSF are strongly associated with an increased risk of severe cerebral hemorrhage and SIRS following surgery. These findings suggest that monitoring CSF immune markers, particularly CD3+T lymphocytes, could serve as valuable predictors for the development of SIRS in critically ill ICH patients and inform post-surgical treatment strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Intracerebral hemorrhage (ICH) is a significant global disease with high mortality and disability. As of now, there is no effective therapy available. Oxidative stress and neuronal apoptosis play essential roles in ICH, determining neuronal survival. In our preliminary studies, we found that Baihui-penetrating-Qubin acupuncture could improve neurological deficits and neuropathological damage in the perihematomal area in ICH rats. The SIRT1/FOXO1 signaling pathway has been reported to mediate antioxidant and anti-neuronal apoptosis. This study aimed to investigate the effects of Baihui-penetrating-Qubin acupuncture on oxidative stress and neuronal apoptosis after ICH and the role of SIRT1/FOXO1 in acupuncture's neuroprotection., Methods: ICH rat models were established by autologous tail blood (50 µL) infusion into the caudate nucleus. EX527, SIRT1-specific inhibitor was intraperitoneally administered 3 days before ICH. Baihui-penetrating-Qubin acupuncture treatment was performed once a day for 30 min after ICH. Neurological deficits were evaluated using the modified neurological severity score (mNSS). Brain edema was evaluated using brain water content. HE staining and Nissl staining were used to evaluate neuropathological damage in the perihematomal area. Terminal deoxynucleotidyl transferase dUTP nick end labeling was used to quantify neuronal apoptosis. Specific kits were used to detect the levels of SOD, CAT, GSH-Px in the brain. The oxidative DNA damage was evaluated using enzyme-linked immunosorbent assay to detect the level of 8-hydroxyguanosine (8-OHdG). Western blot was used to evaluate the expressions of SIRT1, Ac-FOXO1, FOXO1, Bcl-2, and Bax. Immunofluorescence staining was conducted to detect the cellular localization of SIRT1., Results: Baihui-penetrating-Qubin acupuncture improved the neurological deficits and brain edema, reduced the pathological injury and neuronal degeneration in 3 days in the perihematomal area after ICH. Mechanistically, acupuncture reduced oxidative stress injury and neuronal apoptosis via activating SIRT1/FOXO1 pathway. The neuroprotective effects of acupuncture were abolished by injection of the SIRT1 inhibitor EX527., Conclusions: Baihui-penetrating-Qubin acupuncture could reduce oxidative stress and neuronal apoptosis, at least in part, through the SIRT1/FOXO1 signaling pathway, improving neurological deficits and neuropathological damage after ICH. These findings suggest that Baihui-penetrating-Qubin acupuncture is an effective therapy for ICH, as well as targeting SIRT1 signaling to promote neuron survival could be a potential therapeutic strategy., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Intracerebral hemorrhage (ICH) is a major health problem. It is one of the most common types of stroke and results in mortality in approximately half of patients. More than half of the fatalities occur in the first 2 days. In addition to the mass effect after ICH hemorrhage, complex pathophysiological mechanisms such as intracranial vessel vasospasm, microthrombosis, and inflammatory immune reaction also increase brain damage. Both resident (including microglia and astrocytes) and circulating immune cells (including neutrophils, macrophages, and lymphocytes) involved in the inflammatory process. The inflammatory response is especially harmful in the acute phase due to harmful substances secreted by infiltrating immune cells. The inflammatory response also has beneficial effects, especially in the later stages. Their role in pathophysiology makes immune cells important therapeutic targets. General immunosuppressive approaches and depleting cell groups such as neutrophils or keeping them away from the lesion site may not be sufficient to prevent poor outcomes after ICH. This is most likely because they suppress anti-inflammatory activities and pro-inflammatory effects. Instead, directing immune cells to the beneficial subpopulation seems like a more rational solution. The pro-inflammatory N1 subpopulation of neutrophils damages the tissue surrounding ICH. In contrast, the N2 subpopulation is associated with anti-inflammatory reactions and tissue repair. Studies show that when neutrophils are polarized toward the N2 subpopulation, clinical outcomes improve and the volume of the infarct decreases. However, more research is still needed. This study aims to evaluate the role of neutrophils as immunotherapeutic targets in ICH in light of current knowledge., (© 2024. The Author(s), under exclusive licence to The Drug Information Association, Inc.)

Background: Yi-Qi-Huo-Xue Decoction (YQHXD), a traditional Chinese medicine formula, has demonstrated efficacy in the clinical treatment of intracerebral hemorrhage (ICH) for over a decade. Nevertheless, the precise pharmacotherapeutic compounds of YQHXD capable of penetrating into cerebral tissue and the pharmacological underpinnings of YQHXD remain ambiguous., Methods: The active components of YQHXD in rat brains was analyzed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The potential targets, pathways and biological progresses of YQHXD ameliorating ICH induced injury was predicted by network pharmacology. Moreover, collagenase-induced ICH rat model, primary cortex neurons exposed to hemin and molecular docking were applied to validate the molecular mechanisms of YQHXD., Results: Eleven active components of YQHXD were identified within the brains. Employing the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, our investigation concentrated on the roles of autophagy and the BDNF/TrkB signaling pathway in the pharmacological context. The pharmacological results revealed that YQHXD alleviated neurological dysfunction, brain water content, brain swelling, and pathological injury caused by ICH. Meanwhile, YQHXD inhibited autophagy influx and autophagosome in vivo, and regulated cortex neuronal autophagy and TrkB/BDNF pathway both in vivo and in vitro. Subsequently, N-acetyl serotonin (NAS), a selective TrkB agonist, was employed to corroborate the significance of the BDNF/TrkB pathway in this process. The combination of NAS and YQHXD did not further enhance the protective efficacy of YQHXD in ICH rats. Additionally, outcomes of molecular docking analysis revealed that nine compounds of YQHXD exhibited potential regulatory effects on TrkB., Conclusions: Ipsilateral neuronal autophagy and BDNF/TrkB pathway were activated 72 h after ICH. YQHXD effectively resisted injury induced by ICH, which was related with suppression of ipsilateral neuronal autophagy via BDNF/TrkB pathway. This study provides novel insights into the therapeutic mechanisms of traditional Chinese medicine in the context of ICH treatment., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Objectives: Poor immune-nutritional status has been associated with an unfavorable outcome in critical illness. The Osaka prognostic score (OPS) and the Naples prognostic score (NPS), based on inflammatory and nutritional status, has been shown to predict prognosis following cancer and other diseases. The aim of this study was to investigate the relationship between the OPS and NPS and the short-term outcomes of patients with intracerebral hemorrhage (ICH)., Methods: We retrospectively analyzed the clinical data of patients hospitalized with spontaneous ICH (n = 340) at The Second Affiliated Hospital of Chongqing Medical University between August 2016 and August 2021. Inclusion criteria included patients aged between 18 and 70, and if a blood sample was taken for laboratory testing within 24 h of admission (serum C-reactive protein, albumin, total cholesterol, and counts for neutrophils, lymphocytes, and monocytes were collected on admission). Exclusion criteria included a non-spontaneous cause of ICH and patient death during hospitalization. Patients were divided into four groups based on OPS or five groups according to NPS. Outcomes were evaluated by the modified Rankin Scale (mRS) at six months post-ICH hospitalization. An unfavorable outcome was defined as a mRS score ≥ 3., Results: A total of 289 patients met our inclusion criteria. The unfavorable outcome group had older age, a lower Glasgow Coma Scale score, a higher rate of complications and cerebral herniation, a longer hospital stay, and higher OPS and NPS when compared with the favorable outcome group. Univariate analysis showed that both OPS and NPS were strongly correlated with mRS (r = 0.196,P < 0.001; r = 0.244, P = 0.001, respectively). Multivariate analysis further showed that OPS and NPS were both independent predictors of unfavorable outcomes for patients with ICH with adjusted odds ratios of 1.802 (95% confidence interval [CI]:1.140-2.847, P = 0.012) and 1.702 (95% CI: 1.225-2.635, P = 0.02), respectively. The area under the curve (AUC) of NPS for predicting a poor outcome was 0.732 (95% CI: 0.665-0.799), which was similar to the AUC of OPS 0.724 (95% CI: 0.657-0.792)., Conclusions: In this cohort, a higher OPS and NPS on admission was associated with poor outcome at six months following ICH, supporting their potential role as markers for predicting the outcome of patients with ICH., (© 2023. The Author(s).)

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.

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.

Purpose: 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., Methods: 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., Results: 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 (Sensitivity 30-day  = 0.636, 1-Specificity 30 - day  = 0.311; Sensitivity 90-day  = 0.580, 1-Specificity 90-day  = 0.270)., Conclusions: A low ASPECTS-H was an indicator of poor short-term and long-term functional outcomes of ICH.

Phillyrin, a natural plant extract, has significant antioxidant and anti-apoptotic effects. However, its effect on intracerebral hemorrhage (ICH) remains unclear. In this study, we investigated a potential role for phillyrin in the regulation of the oxidative stress and apoptosis induced by ICH. A model of ICH was induced by collagenase IV (0.2 U in 1 μl sterile normal saline) in male C57BL/6J (B6) mice and different doses of phillyrin (5, 15, or 30 mg/kg) were intraperitoneally (i.p.) injected at 30 min, 6 h, and 22 h after modeling. We found that phillyrin significantly reduced neural function and lesion volume, improved injury of white and grey matter around the lesion, decreased apoptosis and oxidative stress, increased the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase 1(HO-1), NADPH quinone oxidoreductase 1 (NQO1) and Superoxide Dismutase-1(SOD-1) in vitro and in vivo, and protected neurons from the stimulation of hemin by promoting Nrf2 nuclear translocation. Treatment with ML385 (Nrf2 inhibitor) completely reversed the protective effects of phillyrin in vivo after ICH injury. Based on our findings, we conclude that phillyrin treatment alleviates ICH injury-induced apoptosis and oxidative stress via activation of the Nrf2 signaling pathway, highlighting a potential role for phillyrin as an ICH therapeutic., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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.

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., (© 2020. The Author(s).)

Dentin matrix protein 1 (DMP1) is an extracellular matrix phosphoprotein that is known to facilitate mineralization of collagen in bone and promote osteoblast/odontoblast differentiation. Blood-brain barrier (BBB) disruption is the major pathogenesis in secondary brain injury after intracerebral hemorrhage (ICH). This study aimed to investigate the expression pattern of DMP1 in the mouse brain and explore the role of DMP1 in BBB disruption and brain injury in a mouse model of ICH. Mice were subjected to autologous blood injection-induced ICH. Immunofluorescence staining, western blot analysis, neurobehavioral tests, brain water content measurements, Evans blue permeability assay, and transmission electron microscopy were performed. Small interfering RNA targeting DMP1 (DMP1 siRNA) was administered at 72 h prior to ICH. Results showed that DMP1 is expressed extensively in the mouse brain, and is upregulated in the ICH model. Administration of DMP1 siRNA effectively ameliorated BBB disruption, attenuated brain edema, and improved neurological function after ICH. Moreover, the expression of zonula occludens-1 (ZO-1) and occludin were upregulated, and matrix metalloproteinase-9 (MMP-9) was downregulated in the ICH model. DMP1 siRNA administration reversed the expression of ZO-1, occludin, and MMP-9. These results demonstrated that DMP1 upregulation plays an essential role in inducing BBB disruption and brain injury after ICH. The inhibition of DMP1 could be a potential therapeutic strategy for ICH treatment., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Necroptosis-induced neuronal damage after intracerebral hemorrhage (ICH) has been documented recently. Previous studies have reported that RIP3 and its complex are recognized as central mediators of necroptosis. In this study, the role of RIP3 in the activation of CaMKII and AIF was investigated., Methods: We induced ICH in C57BL/6 mice by injecting collagenase IV into the basal ganglia. ICH mice were pretreated with the mPTP inhibitor CsA and the CAMKII inhibitor Kn-93, RIP3 siRNA or RIP3 rAAV. Brain edema and neurobehavior were evaluated. The expression of RIP3, p-MLKL, AIF, and CaMKII proteins was evaluated by western blotting, immunofluorescence (IF) and immunoprecipitation (IP)., Results: Significant increases in RIP3, p-MLKL, CaMKII and AIF expression were observed in ICH mice, and RIP3-AIF colocalized in the nucleus. Overexpression of RIP3 by rAAV upregulated AIF expression in both the cytoplasm and nucleus, while CaMKII expression was increased in the cytoplasm. The interaction of RIP3-AIF and RIP3-CaMKII was detected after ICH injury. These complexes were inhibited by CsA with Kn-93 or RIP3 siRNA pretreatment, which reduced brain edema and neurological deficits., Conclusions: Our findings revealed that ICH induced necroptotic neuronal death through the RIP3-CaMKII complex and the RIP3-AIF signaling pathway. Moreover, blockade of mPTP opening could suppress the pathogenesis of necroptosis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Iron has a key role in the activation of the autophagic pathway in rats with intracerebral hemorrhage (ICH), and hepcidin has the ability to reduce brain iron in ICH-rats. We therefore hypothesized that hepcidin might be able to inhibit autophagy by reducing iron in an ICH brain. Here, we investigated the effects of Ad-hepcidin and/or hepcidin peptide on autophagic activities in ICH models in vitro and in vivo. We demonstrated that ad-hepcidin and hepcidin peptide both inhibited hemin-induced increase in LC3-II/LC3-I conversion ratio and reversed the reduction in p62 content in cortical neurons in vitro. We also showed that ad-hepcidin inhibited ICH-induced increase in LC3-II/LC3-I conversion ratio and reversed ICH-induced reduction in p62 content in the brain cortex of rats in vivo. Based on these findings plus previous data on the effects of ad-hepcidin and/or hepcidin peptide on iron contents in ICH models, we suggested that hepcidin-induced inhibition of autophagy might be mediated via reducing iron in hemin-treated neurons in vitro and ICH-rat brain in vivo., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To observe the effect of acupuncture at "Baihui" (GV 20) through "Qubin" (GB 7) on NLRP3 inflammatory corpuscle in rats with intracerebral hemorrhage (ICH), and to explore the action mechanism of acupuncture on promoting the recovery of neural function in rats with ICH., Methods: Forty SPF six-week-old male SD rats were randomly divided into a sham operation group, a model group, a non-acupoint group and an acupuncture group, 10 rats in each group. The rats in the model group, non-acupoint group and acupuncture group were intervened with autologous blood injection to prepare ICH model, while the rats in the sham operation group were only intervened with operation but not injection with autologous blood. About 3 hours after the establishment of the model, the rats in the acupuncture group were intervened with acupuncture at "Baihui" (GV 20) through "Qubin" (GB 7), once every 12 hours, for 7 days; the rats in the non-acupoint group were intervened with acupuncture at the non-acupoint [parallel to the "Baihui" (GV 20), 1 cm next to the midline] on the affected side, and other treatment was the same as the acupuncture group. At the end of the intervention, the composite nerve function score of each group was evaluated; the histomorphology of the hemorrhage penumbra was observed by HE staining; the expression of NLRP3 inflammatory corpuscle in the brain was detected by immunohistochemistry; the relative protein expression levels of NLRP3, interleukin-1β (IL-1β) and interleukin-18 (IL-18) in brain were detected by the method of Western blot., Results: Seven days into intervention, compared with the sham operation group, each item score and total score of composite nerve function in the model group were significantly reduced ( P <0.01, P <0.05). There was edema and karyopyknosis in brain neuron as well as necrocytosis and inflammatory cell infiltration in the model group. Compared with the model group and the non-acupoint group, the total score of composite nerve function and the scores of symmetrical movement of limbs (LS) and proprioception of tentacles (VP) in the acupuncture group were increased ( P <0.01, P <0.05), and the cell necrosis and inflammatory cell infiltration were relieved. Compared with the sham operation group, NLRP3 inflammatory corpuscle expression and the relative protein expression levels of NLRP3, IL-1β and IL-18 in brain tissue in the model group were increased ( P <0.01); compared with the model group and the non-acupoint group, NLRP3 inflammatory corpuscle expression and the relative protein expression levels of NLRP3, IL-1β and IL-18 in brain tissue in the acupuncture group were reduced ( P <0.01)., Conclusion: Acupuncture at "Baihui" (GV 20) through "Qubin" (GB 7) could downregulate the expression of NLRP3, IL-1β and IL-18 in the brain tissue of ICH rats, inhibit the inflammatory response, and promote the recovery of neural function.

N-myc downstream-regulated gene 2 (NDRG2), a newly identified astrocytic stress response gene, is involved in the regulation of astrocytic morphology and function, and has been indicated to be a potential therapeutic target for some central nervous system (CNS) diseases. However, the role of NDRG2 in intracerebral hemorrhage (ICH) remains unknown. Here, we reported that NDRG2 suppression exerted neuroprotection effect against hemorrhagic brain injury in ICH mice and in oxyhemoglobin (OxyHb)-treated cells. Ndrg2 knockout (Ndrg2 -/- ) mice exhibited reduced hematoma volume and neuronal apoptosis in perihematoma although Ndrg2 deficiency showed little effect on the initial hematoma volume after ICH induction by collagenase injection. Moreover, contrary to the increase in NDRG2 expression after ICH, the expression of glutamate transporter 1 (GLT1) in astrocytes was dramatically decreased in WT (Ndrg2 +/+ ) mice, while which could be more maintained in Ndrg2 knockout mice following ICH. Furthermore, in terms of the mechanism of epigenetic regulation of GLT1 by NDRG2, the results showed that NDRG2 directly interacted with NF-κB, and inhibited the nuclear import and DNA binding activity of the NF-κB p65 subunit after OxyHb treatment in primary astrocytes, decreasing GLT1 transcription and impairing glutamate uptake. Overall, our findings indicate that NDRG2 plays a key role in the pathology of ICH by regulating astrocytic GLT1 expression; thus suppressing NDRG2 may be a potential therapeutic target for ICH., (Copyright © 2019. Published by Elsevier B.V.)

Most intracerebral hemorrhage (ICH) survivors have poor long-term outcomes, such as cognitive deficits and depression. Delayed lesions of ICH include neuron loss and white matter injury and the pathology of the lesions involves iron deposition and glial responses, which contribute to depressive-like behavior and cognitive impairment in animals. This study aimed to investigate the effects of FTY720 (0.3 mg/kg/day for 4 weeks) on iron deposition, glial responses, histological abnormalities and behavioral dysfunction in mice with ICH. The primary adverse long-term outcomes in our study of ICH mice were depressive-like behavior and impaired recognition memory. We found that FTY720 safely ameliorated depressive-like behavior and impaired recognition without affecting recovery of grip function and locomotor activity 28 days post-ICH. Moreover, we measured neuron loss, white matter lesions, lesion volume and iron deposition at day 28, which were attenuated in the FTY720-treated group compared to the ICH-control group, without changing initial hematoma volume on day 1 post-ICH. Long-term elevation of glial responses, including microglia activity and astrogliosis with tumor necrosis factor alpha (TNFα) expression was demonstrated by Western blot and immunofluorescence staining, which we found was attenuated by FTY720 treatment. Hence, FTY720 could become a novel therapeutic agent for improving long-term outcomes after ICH., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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.

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., (© 2018 Wiley Periodicals, Inc.)

Background: Experimental animal model studies have shown neuroprotective properties of magnesium. We assessed the relationship between admission magnesium and admission stroke severity and 3-month clinical outcomes in patients with acute intracerebral hemorrhage (ICH)., Methods: The present study included 323 patients with acute ICH who were prospectively identified. Demographic characteristics, lifestyle risk factors, National Institute of Health Stroke Scale (NIHSS) score, hematoma volumes, and other clinical features were recorded at baseline for all participants. Patients were divided into three groups based on the admission magnesium levels (T1: <0.84; T2: 0.84-0.91; T3: ≥0.91 mmol/L). Clinical outcomes were death, poor functional outcome (defined by modified rankin ccale [mRS] scores 3-6) at 3 months., Results: After 3-month follow-up, 40 (12.4%) all-cause mortality and 132 (40.9%) poor functional outcome were documented. Median NIHSS scores for each tertile (T1 to T3) were 8.0, 5.5, and 6.0, and median hematoma volumes were 10.0, 8.05, and 12.4 ml, respectively. There was no significant association between baseline NIHSS scores (P=0.176) and hematoma volumes (P=0.442) in T3 and T1 in multivariable linear regression models. Compared with the patients in T1, those in T3 were associated with less frequency of all-cause mortality [adjusted odds ratio (OR), 0.10; 95% confidence interval (CI), 0.02-0.54; P-trend=0.010] but not poor functional outcome (adjusted OR, 1.80; 95%CI, 0.71-4.56; P-trend=0.227) after adjustment for potential confounders., Conclusion: Elevated admission serum magnesium level is associated with lower odds of mortality but not poor functional outcome at 3 months in patients with acute ICH., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Primary intraventricular hemorrhage (PIVH) is a rare type of Intracerebral Hemorrhage (ICH), which is poorly understood. This study aimed to investigate gender differences in patients' characteristics, management and outcome at discharge and 90 days after PIVH., Methods: Consecutive patients with PIVH from a single center in China were enrolled over a 7- year period. Gender differences in demographics, risk factors, etiological subtypes, treatment, and outcomes were examined. The logistic regression models were used in the study to identify the predictors of poor outcome., Results: In total, 174 patients were analyzed, and 77 (44.3%) of them were women. Women with PIVH were younger (p = 0.047), with lower systolic and diastolic blood pressure (p = 0.02 and p = 0.004, respectively). They had more cases caused by Moyamoya disease (p = 0.038). There were fewer patients with hypertension (p = 0.008), smoking (p＜0.001), chronic alcoholism (p＜0.001), harbored lower hemoglobin (p＜0.001) and Absolute Monocyte Count (AMC) (p = 0.04) at admission compared with men. There were no differences between female and male patients regarding the mortality and poor outcome in the multivariable-adjusted models ((OR = 0.57; 95% CI, 0.15-2.14) and (OR = 0.86; 95% CI, 0.32-2.37), respectively). In subgroup analysis after adjustment, the gender specific independent predictors for unfavorable outcome were higher with a Graeb score (OR = 1.78; 95% CI, 1.01-3.13) or AMC (OR = 9.66; 95% CI, 1.20-12.87) in women, and lower Glasgow coma scale (GCS) score (OR = 0.64; 95% CI, 0.47-0.87) or acute hydrocephalus (OR = 0.17; 95% CI, 0.03-0.86) in men., Conclusion: Women with PIVH exhibit some distinctive baseline features compared with men. The gender difference of the PIVH does not appear to affect the neurological outcome. The predictors of poor outcomes are Graeb score and AMC in women and GCS score and acute hydrocephalus in men., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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., (© 2018 Wiley Periodicals, Inc.)

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.

A 17-year-old woman was urgently transported to our hospital due to consciousness disturbance. A blood examination revealed intracerebral hemorrhage, WBC 233,800/l, blasts 93%, and disseminated intravascular coagulation. The results of bone-marrow aspiration indicated acute myeloid leukemia (M2 in FAB classification) with t (7;11) (p15;p15) and the resulting chimeric gene NUP98-HOXA9 and with FLT3-ITD. Following hematoma evacuation, induction therapy was initiated and the leukocytes in the cerebrospinal fluid observed in the spinal drainage were monitored. Because they increased on days 5 and 9 after the completion of induction therapy, intrathecal chemotherapy (IT) was performed; this finally contributed to controlling AML in the central nervous system (CNS), together with the restoration of normal hematopoiesis. Subsequently, after complete molecular remission with consolidation therapies containing high-dose cytarabine, a bone-marrow transplantation with a myeloablative regimen was conducted from a 1-allele mismatched sibling donor. Finally, the patient was discharged without major sequela on day 228 after the first visit. The management of CNS disease in AML with intracerebral hemorrhage remains unclear. Our case suggests that IT at the appropriate time based on the monitored number of cerebrospinal fluid leukocytes could be useful in controlling AML in the CNS after intracerebral hemorrhage.

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.

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.

Unlabelled: Peroxisome-proliferator-activated receptor co-activator-1α (PGC-1α) is a transcriptional co-activator that coordinately regulates genes required for mitochondrial biogenesis, which stimulates mitochondrial activity. It is also a major factor in the up-regulation of antioxidant activities that are a response to oxidative stress. However, the role of PGC-1α after intracerebral hemorrhage (ICH) has not been studied. The purpose of the present work was to investigate the effects and mechanism of PGC-1α after ICH in the brain. Brain injury was induced by injecting autologous arterial blood (50μL) into the rat brain. PGC-1α siRNAs were injected into rat brains 24h prior to ICH. Then, 72h after ICH, brains were collected for investigation. Post-assessment included western blot analysis, RT-PCR assay, neurobehavioral function testing, measurement of brain water content, high-performance liquid chromatography (HPLC), and projection electron microscopy on ICH rat models. The concentration of PGC-1α was higher in the ipsilateral striatum after ICH, peaking around 72h after ICH. The expression of NRF-1, TFAM, SOD2, UCP2, mitochondrial DNA, ATP concentration, mitochondrial quantity, and brain water content were increased 72h after ICH. However, the neurological score was decreased 72h after ICH. Treatment with PGC-1α siRNAs significantly decreased the neurological score, ATP concentration, number of mitochondria, expression of NRF-1, TFAM, SOD2, UCP2, and mitochondrial DNA, and increased brain water content and formation of mitochondrial myelin layer structures. In conclusion, our data suggest that PGC-1α protects rat brains via a mitochondrial pathway following ICH., Key Words: PGC-1α intracerebral hemorrhage(ICH); mitochondrial; neuroprotection., (Copyright © 2016. Published by Elsevier B.V.)

Background: The kidney-brain interaction has been a topic of growing interest. Past studies of the effect of kidney function on intracerebral hemorrhage (ICH) outcomes have yielded inconsistent findings. Although the second, main phase of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) suggests the effectiveness of early intensive blood pressure (BP) lowering in improving functional recovery after ICH, the balance of potential benefits and harms of this treatment in those with decreased kidney function remains uncertain., Study Design: Secondary analysis of INTERACT2, which randomly assigned patients with ICH with elevated systolic BP (SBP) to intensive (target SBP<140mmHg) or contemporaneous guideline-based (target SBP<180mmHg) BP management., Setting & Participants: 2,823 patients from 144 clinical hospitals in 21 countries., Predictors: Admission estimated glomerular filtration rates (eGFRs) of patients were categorized into 3 groups based on the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation: normal or high, mildly decreased, and moderately to severely decreased (>90, 60-90, and <60mL/min/1.73m(2), respectively)., Outcomes: The effect of admission eGFR on the primary outcome of death or major disability at 90 days (defined as modified Rankin Scale scores of 3-6) was analyzed using a multivariable logistic regression model. Potential effect modification of intensive BP lowering treatment by admission eGFR was assessed by interaction terms., Results: Of 2,623 included participants, 912 (35%) and 280 (11%) had mildly and moderately/severely decreased eGFRs, respectively. Patients with moderately/severely decreased eGFRs had the greatest risk for death or major disability at 90 days (adjusted OR, 1.82; 95% CI, 1.28-2.61). Effects of early intensive BP lowering were consistent across different eGFRs (P=0.5 for homogeneity)., Limitations: Generalizability issues arising from a clinical trial population., Conclusions: Decreased eGFR predicts poor outcome in acute ICH. Early intensive BP lowering provides similar treatment effects in patients with ICH with decreased eGFRs., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Urocortin exerts neuroprotective effects in intracerebral hemorrhage (ICH) of rats. For pre-clinical trial, we intended to study the neuroprotective efficacy of human UCN (hUCN)-1, -2 and -3 in treating ICH rats. ICH was induced by infusing bacterial collagenase VII (0.23 U in sterile saline) to the striatum. The hUCN-1, -2, and -3 were administrated (2.5μg/kg, i.p.) at 1h after ICH insult, respectively. Neurological deficits were evaluated by modified Neurological Severity Scores. Brain edema and hematoma expansion was evaluated by coronal T2-WI and DWI magnetic resonance imaging on 1, 3, 6, 24, and 56h after ICH insult. Blood-brain barrier permeability was evaluated by Evans blue assay on day 3 after ICH. Brain lesion volume was evaluated by morphormetric measurement on day 7 after ICH. Our results demonstrated that the hUCN-1 significantly reduced hematoma, blood-brain barrier disruption and neurological deficits on day 3, and brain lesion volume on day 7 after ICH insult. The prediction of secondary structure of the hUCNs clarifies that the percentage of alpha-helix, random coil and extended strand between rat-UCN (rUCN)-1 and hUCN-1 are the same. The structure similarity between human- and rat-UCN-1 may be one of the reasons that both can exert similar therapeutic potential in ICH rats., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Healthy SD rats were randomly divided into 3 groups as sham operation (group A), ICH (group B), and HBO2 (group C). The behavioral change and angiogenesis in brain tissue of rats in each group were observed. The protein expression of PCNA, vWF, HIF1-α, and VEGF in rat brain was measured by immunohistochemistry, while the mRNA expression level of HIF1-α and VEGF was determined using quantitative real-time PCR. This study has investigated the effect of HBO2 on intracephalic angiogenesis in rats with intracerebral hemorrhage (ICH). There were significant differences in behavior score between HBO2 and ICH groups at 14, 21, and 28 days. A large number of vessel-like structures and microvessels were observed in perihematomal brain tissues in HBO2 group. There were significant differences in HIF1-α and VEGF protein and HIF1-α mRNA level between HBO2 and ICH groups at 14, 21, and 28 days; at 7, 14, 21, and 28 days, the differences in PCNA and vWF protein expression between the 2 groups were statistically significant. At 21 and 28 days, the expression levels of VEGF mRNA in the 2 groups differed significantly from each other. Our results indicate that HBO2 can significantly promote the expression of HIF1-α and VEGF at both mRNA and protein levels in rats with ICH, increase the protein expression of both PCNA and vWF, promote the formation of new blood vessels, and promote the recovery of behavioral ability, hence resulting in a rapid rehabilitation., (Copyright © 2014 Elsevier B.V. All rights reserved.)

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.

Transplantation of induced pluripotent stem cells (iPSCs) has shown promising therapeutic effects for ischemic stroke. However, it is not clear if this treatment would promote recovery after intracerebral hemorrhage (ICH). In this study, we investigated the functional outcome of iPSCs transplantation in experimental ICH in rats. IPSCs were derived from an ICH patient's fibroblasts and were injected into the ipsilateral side of ICH in rats. IPSCs transplantation significantly improved the neurological functions after ICH as compared to vehicle and fibroblast injection. The grafted iPSCs migrated into brain tissue around the hematoma, survived after 4 weeks of transplantation, and exhibited the neural cell-specific biomarkers nestin, β-tubulin, and GFAP. Immunohistochemical staining showed that the densities of brain derived neurophic factors (BDNF)-positive cells and vascular endothelial growth factor (VEGF)-positive cells were significantly increased around the hemorrhagic brain tissues of iPSCs-treated rats. In addition, iPSCs treatment increased the protein expression of BDNF and VEGF in the surrounding region of hematoma. These findings demonstrate that the transplantation of ICH patient-derived iPSCs contributes toward the improved neurological function in experimental ICH rats. The mechanisms are possibly due to neuronal replacement and enhanced secretion of neurophic factors. Our data suggest that transplantation of ICH patient-derived iPSCs may be a therapeutic strategy for hemorrhagic stroke., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: We aimed to investigate the expression of T cell immunoglobulin and mucin domain 3 (Tim-3) on peripheral blood cells in spontaneous intracerebral hemorrhage (ICH) patients and to analyze its clinical significance., Design and Methods: Tim-3 expression on peripheral immunocytes from ICH patients and healthy volunteers was measured by flow cytometry. The correlation between Tim-3 expression and the clinical indices was estimated using linear regression., Results: Tim-3 expressions on peripheral CD3⁺ T cells and CD8⁺ T cells in ICH patients are significantly downregulated, while Tim-3 expressions on CD14⁺ monocytes and CD16⁺CD56⁺ NK cells are increased. Furthermore, Tim-3 expression on peripheral CD8⁺ cells was negatively correlated with the inflammatory response, the disease severity and the outcome of ICH patients. However, there was no relationship between Tim-3 expression and blood glucose concentration., Conclusions: Altered expression of Tim-3 might play an important role in the pathogenesis of ICH, demonstrating that Tim-3 might be a novel candidate molecule for prognosis evaluation of ICH patients., (Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Specific targeted therapy for intracerebral hemorrhage (ICH), which has high disability and case-fatality rate, is currently not available. Induced pluripotent stem cells (iPSCs) generated from somatic cells of ICH patients have therapeutic potential for individualized cerebral protection. While, whether ICH patient-originated iPSCs could differentiate into neuro-epithelial-like stem (NES) cells and whether such NES cells could improve functional recovery in the hemorrhage-injured brain are unclear. Here, we showed that fibroblasts from an ICH patient can be efficiently reprogrammed to iPSCs by lentiviral vectors carrying defined transcription factors (OCT4, SOX2, KLF4, and c-MYC). These iPSCs have the typical morphology, surface antigens, capability of self-renewal and differentiating into cell types of all three embryonic germ layers that are similar to human embryonic stem cells (hESCs). Using defined serum-free neural differentiation medium, we induced the iPSCs differentiate into NES cells. Subsequently, the NES cells from ICH patient-originated iPSCs were transplanted into the perihematoma of rats with experimental ICH injury. Intriguingly, recovery of neurological dysfunction in experimental ICH rats was observed post-NES cells graftage. Transplanted NES cells migrated to the surrounding area of hematoma, survived and differentiated into neuron-like cells. Our study demonstrates that the transplantation of human iPS-originated NES cells is an effective approach of treating ICH injury and the improvement of neural function is partially due to neuronal replacement and regeneration., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: This study aims to evaluate the clinical significance of ultrasound-based measurement of optic nerve sheath diameter (ONSD) in predicting intracerebral hemorrhage (ICH) complicated by cerebral-cardiac syndrome (CCS). Methods: Patients with ICH and who were treated in the intensive care unit (ICU) at Shijiazhuang People's Hospital between October 2021 and November 2022 were included in this study. Participants were divided into two groups: those with CCS and those without. Various clinical parameters, including sex, age, electrocardiogram (ECG) findings, myocardial markers, B-type natriuretic peptide (BNP) levels, Glasgow Coma Scale (GCS) score, ONSD, hematoma volume, and midline shift, were assessed. A binary logistic regression model and receiver operating characteristic (ROC) curve analysis were employed to determine the predictive value of each risk factor for ICH complicated by CCS. Results: ONSD measurements differed significantly between males and females, with males exhibiting larger ONSD values. Additionally, significant differences were observed in ONSD, hematoma volume, midline shift, and GCS scores between the CCS and non-CCS groups. A direct correlation was identified between ONSD and both hematoma volume and midline shift. Multiple regression analysis demonstrated that ONSD, hematoma volume, and GCS score are independent risk factors for predicting ICH complicated by CCS. ROC curve analysis for ONSD in predicting ICH with CCS revealed an area under the curve (AUC) of 0.80, with an optimal cutoff value of 5.88 cm, yielding a sensitivity of 83% and a specificity of 79%. When ONSD, hematoma volume, and GCS score were combined, the predictive accuracy improved, with an AUC of 0.880. Conclusion: Males tend to have larger ONSD measurements compared to females. Ultrasound is a valuable tool for measuring ONSD, comparable to computed tomography, and is useful in detecting intracranial hypertension and mass effect. ONSD, hematoma volume, and GCS score are independent predictors of ICH complicated by CCS, and their combined use enhances predictive accuracy. [ABSTRACT FROM AUTHOR]

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]

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]

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]

• A novel symmetric independent antenna pair (SIAP) sensor was designed for precise detection and monitoring of ischemia stroke (IS). • The SIAP sensor demonstrates its capability to differentiate between intracerebral hemorrhage and cerebral ischemia. • Animal experiments have confirmed that the SIAP sensor can effectively detect compensatory increases in cerebral blood flow on the healthy hemisphere following IS. Unlike intracerebral hemorrhage (ICH), the initial intracranial dielectric constant changes in IS are subtle and difficult to detect. Considering that the brain is approximately axisymmetric and the IS-affected hemisphere does not impact the healthy hemisphere, this study proposes a symmetric independent antenna pair (SIAP) sensor. The SIAP sensor consists of two inverted F-antennas positioned symmetrically at 150°, with additional shielding on the ground plane to minimize crosstalk. A realistic brain anatomical model was developed to analyze its Front to Back Ratio (FBR) performance and electromagnetic (EM) wave energy distribution. Subsequently, electromagnetic simulation experiments specific to IS were conducted. Additionally, experiments on rabbits with IS and ICH were carried out. The observed trends in S11 amplitude changes between the ICH and IS groups were distinct, with changes significantly higher in the ICH group compared to the IS group, yet both markedly higher than in the healthy state. This further validates the sensor's capacity to differentiate between ICH and IS. Notably, animal experiments have underscored the sensor's capacity to identify compensatory increases in cerebral blood flow in the unaffected hemisphere post-cerebral ischemia. These findings underscore the potential of the SIAP sensor as a novel approach for swift and accurate IS diagnosis and real-time monitoring. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) exhibits high prevalence and mortality, but current treatments remain suboptimal. Traditional Chinese medicine (TCM) has long been effectively used for TBI intervention. Moreover, the recently discovered iron-dependent cell death pathway, known as ferroptosis, characterized by lipid peroxidation, as a key target in TCM-based treatments for TBI. This review provides a comprehensive overview of the latest advancements in TCM strategies targeting ferroptosis in TBI therapy, covering natural product monomers, classic formulas, and acupuncture/moxibustion. The review also addresses current challenges and outlines future research directions to further advance the development and application of TBI management strategies. • Several novel targets are involved in ferroptosis following TBI. • TCM shows significant effectiveness in treating TBI. • TCM can modulate both classical pathways and novel ferroptosis targets in TBI. • TCM provides alternative and personalized treatment options for TBI patients. [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]

The management of intracerebral hemorrhage (ICH) requires prompt diagnostic assessment and recognition. Accurate localization and categorization of ICH-type is crucial. There are two main categories of ICH: 1) hemorrhagic stroke (HS), which occurs in the deeper or subcortical regions of the brain, where the arterial network tapers to fine end-arteries, and, 2) cerebral amyloid angiopathy hemorrhage (CAAH), which occurs at the superficial or cortical-subcortical region of the grey and white matter junction. Computed tomography (CT) and magnetic resonance imaging (MRI) are the most used imaging tools in diagnosing ICH. However, availability, time, and cost often prevent emergent MRI use. Therefore, CT remains the primary tool in the diagnosis of ICH. The assessment of imaging studies is time-dependent, and a radiologist should do a detailed diagnostic evaluation. Human error can occur in a pressured clinical setting, even for highly trained medical professionals. Assisted or automated computer-aided analysis of CT/MRI may help to reduce the assessment time, improve the diagnostic accuracy, better differentiate between types of ICH, and reduce the risk of human errors. This review evaluates CT and MRI's role in distinguishing between the two varieties of ICH-HS and CAAH. It focuses on how CT could be utilized as the preferred diagnostic tool. In addition, we discuss the role of automation using machine learning (ML) and the role or advantages of ML in the automated assessment of CT for the detection and classification of HS and CAAH. We have included our observations for future research and the requirements for further evaluation. [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]