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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]

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]

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

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Warfarin-related traumatic intracerebral hemorrhage (ICH) is often fatal, yet timely evaluation and treatment can improve outcomes. Our study describes the process of developing and implementing a protocol to guide the care of patients with traumatic brain injury (TBI) on preinjury warfarin developed by nurses across several service lines at our Level I trauma center over a 6-month period. Further, we evaluated its efficacy by examining records of adult patients with TBI on preinjury warfarin admitted 1 year before and after protocol implementation. Efficacy was defined as activation rates, receipt and time to head computed tomography (CT) scan and international normalization ratio (INR), and receipt and time to fresh frozen plasma (FFP) administration in patients with ICH with an INR more than 1.5, as per protocol. A subset analysis examined patients with and without an ICH. Outcomes were compared using univariate analyses. One hundred seventy-eight patients were included in the study; 90 (50.6%) were admitted before and 88 (49.4%) after implementation. After implementation, there were improvements in activation rates (34.4% vs. 65.9%; p < .001), the frequency of head CT scans (55.6% vs. 83.0%; p < .001), time to INR (24.0 min vs. 15.0 min; p < .05), and, for patients with ICH with an INR 1.5 or more, decreased time to FFP (157.0 vs. 90.5; p < .05). In conclusion, our protocol led to a more efficient process of care for patients with TBI on warfarin. We believe the implementation process, managed by a dedicated group of nurses across several service lines, substantially contributed to the success of the protocol. [ABSTRACT FROM AUTHOR]

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 (2.5 μg/kg, i.p.) at 1 h 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 56 h 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. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We performed this study to investigate the effect of blood pressure control in ultra-early basal ganglia intracerebral hemorrhage. PATIENTS AND METHODS: 120 patients with ultra-early basal ganglia intracerebral hemorrhage were randomly divided into experimental group (strengthened antihypertensive) and control (normal antihypertensive). Each group consists of 60 patients, whose contractive pressure were controlled by intravenous antihypertensive drugs among 130-140 mmHg and 160-180 mmHg respectively for 24h, after 1h of beginning treatment. They were all evaluated by NIH Stroke Scale (NIHSS) before and after the treatment. Cranial CT, hematoma volume, hematoma enlargement, edema volume, serum matrix metalloproteinase-9 level were performed and compared between groups. RESULTS: After 24h, hematoma volume and hematoma enlargement in the experimental group was significantly lower than control (p < 0.05). After 14 days, NIHSS score in the experimental group was significantly lower than control (p < 0.05). Cerebral edema amount and serum MMP-9 level in the experimental group were significantly lower than control after 5 days and 14 days. CONCLUSIONS: Ultra-early basal ganglia intracerebral hemorrhage can remarkably reduce hematoma enlargement, cerebral edema, serum MMP-9 level, and improve the neurological function. [ABSTRACT FROM AUTHOR]

Summary: Human umbilical cord blood (HUCB) is now considered as a valuable source for stem cell-based therapies. Previous studies showed that intravascular injection of the HUCB significantly improves neurological functional recovery in a model of intracerebral hemorrhage (ICH). To extend these findings, we examined the behavioral recovery and injured volume in the presence of increasing doses of human umbilical cord blood derived mononuclear cells (HUC-MCs) after intracerebral hemorrhage in rats. The experimental ICH was induced by intrastriatal administration of bacterial collagenase IV in adult rats. One day after the surgery, the rats were randomly divided into 4 groups to receive intravenously either BrdU positive human UC-MCs (4×106, 8×106 and 16×106 cells in 1ml saline, n =10, respectively) as treated groups or the same amount of saline as lesion group (n =10). There was also one group (control n =10) that received only the vehicle solution of collagenase. The animals were evaluated for 14 days with modified limb placing and corner turn tests. The transplanted human UC-MCs were also detected by immunohistochemistry with labeling of BrdU. Two weeks after infusion, there was a significant recovery in the behavioral performance when 4×106 or more UC-MCs were delivered (P <0.05–0.001). Injured volume measurements disclosed an inverse relationship between UC-MCs dose and damage reaching significance at the higher UC-MCs doses. Moreover, human UC-MCs were localized by immunohistochemistry only in the injured area. Intravenously transplanted UC-MCs can accelerate the neurological function recovery of ICH rat and diminish the striatum lesion size by demonstrating a dose relationship between them. [Copyright &y& Elsevier]

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

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. [ABSTRACT FROM AUTHOR]