Search

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. [ABSTRACT FROM AUTHOR]

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

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

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

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

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

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

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

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

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

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

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

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

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

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