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Circulation Research Apr 2022Intracerebral hemorrhage (ICH) is a devastating form of stroke with high morbidity and mortality. This review article focuses on the epidemiology, cause, mechanisms of... (Review)
Review
Intracerebral hemorrhage (ICH) is a devastating form of stroke with high morbidity and mortality. This review article focuses on the epidemiology, cause, mechanisms of injury, current treatment strategies, and future research directions of ICH. Incidence of hemorrhagic stroke has increased worldwide over the past 40 years, with shifts in the cause over time as hypertension management has improved and anticoagulant use has increased. Preclinical and clinical trials have elucidated the underlying ICH cause and mechanisms of injury from ICH including the complex interaction between edema, inflammation, iron-induced injury, and oxidative stress. Several trials have investigated optimal medical and surgical management of ICH without clear improvement in survival and functional outcomes. Ongoing research into novel approaches for ICH management provide hope for reducing the devastating effect of this disease in the future. Areas of promise in ICH therapy include prognostic biomarkers and primary prevention based on disease pathobiology, ultra-early hemostatic therapy, minimally invasive surgery, and perihematomal protection against inflammatory brain injury.
Topics: Cerebral Hemorrhage; Humans; Hypertension; Minimally Invasive Surgical Procedures; Risk Factors; Stroke
PubMed: 35420918
DOI: 10.1161/CIRCRESAHA.121.319949 -
F1000Research 2019Intracerebral hemorrhage (ICH) is a stroke subtype associated with significant morbidity and mortality. The purpose of this review is to provide an update on important... (Review)
Review
Intracerebral hemorrhage (ICH) is a stroke subtype associated with significant morbidity and mortality. The purpose of this review is to provide an update on important research on ICH over the past three years. Topics covered include risk factors, imaging predictors of hematoma expansion, scoring schema to predict hematoma expansion, hemostatic therapies, acute blood pressure lowering, intraventricular administration of alteplase for intraventricular hemorrhage, and the current status of surgical therapies.
Topics: Blood Pressure; Cerebral Hemorrhage; Hematoma; Humans; Risk Factors
PubMed: 30906532
DOI: 10.12688/f1000research.16357.1 -
EBioMedicine Feb 2022Intracerebral haemorrhage (ICH) is the second most common type of stroke and a major cause of mortality and disability worldwide. Despite advances in surgical... (Review)
Review
Intracerebral haemorrhage (ICH) is the second most common type of stroke and a major cause of mortality and disability worldwide. Despite advances in surgical interventions and acute ICH management, there is currently no effective therapy to improve functional outcomes in patients. Recently, there has been tremendous progress uncovering new pathophysiological mechanisms underlying ICH that may pave the way for the development of therapeutic interventions. Here, we highlight emerging targets, but also existing gaps in preclinical animal modelling that prevent their exploitation. We particularly focus on (1) ICH aetiology, (2) the haematoma, (3) inflammation, and (4) post-ICH pathology. It is important to recognize that beyond neurons and the brain, other cell types and organs are crucially involved in ICH pathophysiology and successful interventions likely will need to address the entire organism. This review will spur the development of successful therapeutic interventions for ICH and advanced animal models that better reflect its aetiology and pathophysiology.
Topics: Animals; Brain; Cerebral Hemorrhage; Hematoma; Humans; Inflammation; Stroke
PubMed: 35158309
DOI: 10.1016/j.ebiom.2022.103880 -
Emergency Medicine Clinics of North... Nov 2016Intracerebral hemorrhage (ICH) is the deadliest type of stroke and up to half of patients die in hospital. Blood pressure management, coagulopathy reversal, and... (Review)
Review
Intracerebral hemorrhage (ICH) is the deadliest type of stroke and up to half of patients die in hospital. Blood pressure management, coagulopathy reversal, and intracranial pressure control are the mainstays of acute ICH treatment. Prevention of hematoma expansion and minimally invasive hematoma evacuation are promising therapeutic strategies under investigation. This article provides an updated review on ICH diagnosis and management in the emergency department.
Topics: Acute Disease; Brain; Cerebral Hemorrhage; Computed Tomography Angiography; Emergency Service, Hospital; Humans; Magnetic Resonance Imaging; Prognosis
PubMed: 27741993
DOI: 10.1016/j.emc.2016.06.010 -
Neurotherapeutics : the Journal of the... Oct 2020Spontaneous intracerebral hemorrhage (ICH) results in high rates of morbidity and mortality, with intraventricular hemorrhage (IVH) being associated with even worse... (Review)
Review
Spontaneous intracerebral hemorrhage (ICH) results in high rates of morbidity and mortality, with intraventricular hemorrhage (IVH) being associated with even worse outcomes. Therapeutic interventions in acute ICH have continued to emerge with focus on arresting hemorrhage expansion, clot volume reduction of both intraventricular and parenchymal hematomas, and targeting perihematomal edema and inflammation. Large randomized controlled trials addressing the effectiveness of rapid blood pressure lowering, hemostatic therapy with platelet transfusion, and other clotting complexes and hematoma volume reduction using minimally invasive techniques have impacted clinical guidelines. We review the recent evolution in the management of acute spontaneous ICH, discussing which interventions have been shown to be safe and which may potentially improve outcomes.
Topics: Antifibrinolytic Agents; Antihypertensive Agents; Blood Pressure; Cerebral Hemorrhage; Hemostasis; Humans; Minimally Invasive Surgical Procedures
PubMed: 32720246
DOI: 10.1007/s13311-020-00902-w -
Lancet (London, England) Jun 2016Platelet transfusion after acute spontaneous primary intracerebral haemorrhage in people taking antiplatelet therapy might reduce death or dependence by reducing the... (Comparative Study)
Comparative Study Randomized Controlled Trial
Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial.
BACKGROUND
Platelet transfusion after acute spontaneous primary intracerebral haemorrhage in people taking antiplatelet therapy might reduce death or dependence by reducing the extent of the haemorrhage. We aimed to investigate whether platelet transfusion with standard care, compared with standard care alone, reduced death or dependence after intracerebral haemorrhage associated with antiplatelet therapy use.
METHODS
We did this multicentre, open-label, masked-endpoint, randomised trial at 60 hospitals in the Netherlands, UK, and France. We enrolled adults within 6 h of supratentorial intracerebral haemorrhage symptom onset if they had used antiplatelet therapy for at least 7 days beforehand and had a Glasgow Coma Scale score of at least 8. With use of a secure web-based system that concealed allocation and used biased coin randomisation, study collaborators randomly assigned participants (1:1; stratified by hospital and type of antiplatelet therapy) to receive either standard care or standard care with platelet transfusion within 90 min of diagnostic brain imaging. Participants and local investigators giving interventions were not masked to treatment allocation, but allocation was concealed from outcome assessors and investigators analysing data. The primary outcome was shift towards death or dependence rated on the modified Rankin Scale (mRS) at 3 months, and analysed by ordinal logistic regression, adjusted for stratification variables and the Intracerebral Haemorrhage Score. The primary analysis was done in the intention-to-treat population and safety analyses were done in the intention-to-treat and as-treated populations. This trial is registered with the Netherlands Trial Register, number NTR1303, and is now closed.
FINDINGS
Between Feb 4, 2009, and Oct 8, 2015, 41 sites enrolled 190 participants. 97 participants were randomly assigned to platelet transfusion and 93 to standard care. The odds of death or dependence at 3 months were higher in the platelet transfusion group than in the standard care group (adjusted common odds ratio 2·05, 95% CI 1·18-3·56; p=0·0114). 40 (42%) participants who received platelet transfusion had a serious adverse event during their hospital stay, as did 28 (29%) who received standard care. 23 (24%) participants assigned to platelet transfusion and 16 (17%) assigned to standard care died during hospital stay.
INTERPRETATION
Platelet transfusion seems inferior to standard care for people taking antiplatelet therapy before intracerebral haemorrhage. Platelet transfusion cannot be recommended for this indication in clinical practice.
FUNDING
The Netherlands Organisation for Health Research and Development, Sanquin Blood Supply, Chest Heart and Stroke Scotland, French Ministry of Health.
Topics: Adult; Aged; Aged, 80 and over; Cerebral Hemorrhage; Europe; Female; Humans; Length of Stay; Male; Middle Aged; Platelet Aggregation Inhibitors; Platelet Transfusion; Stroke; Treatment Outcome
PubMed: 27178479
DOI: 10.1016/S0140-6736(16)30392-0 -
Stroke Jul 2022Cardiovascular events after primary intracerebral hemorrhage (ICH) have emerged as a leading cause of poor functional outcomes and mortality during the long-term... (Review)
Review
Cardiovascular events after primary intracerebral hemorrhage (ICH) have emerged as a leading cause of poor functional outcomes and mortality during the long-term recovery after an ICH. These events encompass arterial ischemic events such as ischemic stroke and myocardial infarction, arterial hemorrhagic events that include recurrent ICH, and venous thrombotic events such as venous thromboembolism. The purpose of this review is to summarize the cardiovascular complications after ICH, epidemiology and associated risk factors, and their impact on ICH outcomes. Additionally, we will highlight possible pathophysiological mechanisms to explain the short- and long-term increased risks of ischemic and hemorrhagic events after ICH. Finally, we will highlight potential secondary stroke and venous thrombotic prevention strategies often not considered after ICH, balanced against the risk of ICH recurrence.
Topics: Cerebral Hemorrhage; Humans; Myocardial Infarction; Risk Factors; Stroke; Venous Thromboembolism
PubMed: 35674043
DOI: 10.1161/STROKEAHA.122.036884 -
Journal of Translational Medicine Mar 2023Owing to metabolic disequilibrium and immune suppression, intracerebral hemorrhage (ICH) patients are prone to infections; according to a recent global analysis of...
BACKGROUND
Owing to metabolic disequilibrium and immune suppression, intracerebral hemorrhage (ICH) patients are prone to infections; according to a recent global analysis of stroke cases, approximately 10 million new-onset ICH patients had experienced concurrent infection. However, the intrinsic mechanisms underlying the effects of infection related peripheral inflammation after ICH remain unclear.
METHODS
Lipopolysaccharide (LPS) was intraperitoneally injected into ICH model mice to induce peripheral inflammation. Neurobehavioral deficits, blood‒brain barrier (BBB) disruption, and the expression of CCR5, JAK2, STAT3, and MMP9 were evaluated after treatment with recombinant CCL5 (rCCL5) (a CCR5 ligand), maraviroc (MVC) (an FDA-approved selective CCR5 antagonist), or JAK2 CRISPR plasmids.
RESULTS
Our study revealed that severe peripheral inflammation increased CCL5/CCR5 axis activation in multiple inflammatory cell types, including microglia, astrocytes, and monocytes, and aggravated BBB disruption and neurobehavioral dysfunction after ICH, possibly in part through the JAK2/STAT3 signaling pathway.
CONCLUSIONS
CCR5 might be a potential target for the clinical treatment of infection-induced exacerbation of BBB disruption following ICH.
Topics: Animals; Mice; Astrocytes; Blood-Brain Barrier; Cerebral Hemorrhage; Inflammation; Stroke
PubMed: 36918921
DOI: 10.1186/s12967-023-04044-3 -
CNS Neuroscience & Therapeutics Oct 2019Intracerebral hemorrhage (ICH) is a cerebrovascular disorder with high mortality and disability rates. Although a lot of effort has been put in ICH, there is still no... (Review)
Review
Intracerebral hemorrhage (ICH) is a cerebrovascular disorder with high mortality and disability rates. Although a lot of effort has been put in ICH, there is still no effective treatment for this devastating disease. Recent studies suggest that oligodendrocytes play an important role in brain repair after ICH and thus may be targeted for the therapies of ICH. Here in this review, we first introduce the origin, migration, proliferation, differentiation, and myelination of oligodendrocytes under physiological condition. Second, recent findings on how ICH affects oligodendrocyte biology and function are reviewed. Third, potential crosstalk between oligodendrocytes and other cells in the brain is also summarized. Last, we discuss the therapeutic potential of oligodendrocyte-based treatments in ICH. Our goal is to provide a comprehensive review on the biology and function of oligodendrocytes under both physiological and ICH conditions.
Topics: Brain; Cell Differentiation; Cell Movement; Cerebral Hemorrhage; Humans; Oligodendroglia
PubMed: 31410988
DOI: 10.1111/cns.13193 -
Translational Stroke Research Apr 2023In patients with spontaneous intracerebral hemorrhage caused by different vasculopathies, cerebral microinfarcts have the same aspect on MRI and the same applies to...
In patients with spontaneous intracerebral hemorrhage caused by different vasculopathies, cerebral microinfarcts have the same aspect on MRI and the same applies to cerebral microbleeds. It is unclear what pathological changes underlie these cerebral microinfarcts and cerebral microbleeds. In the current study, we explored the histopathological substrate of these lesions by investigating the brain tissue of 20 patients (median age at death 77 years) who died from ICH (9 lobar, 11 non-lobar) with a combination of post-mortem 7-T MRI and histopathological analysis. We identified 132 CMIs and 204 CMBs in 15 patients on MRI, with higher numbers of CMIs in lobar ICH patients and similar numbers of CMBs. On histopathology, CMIs and CMBs were in lobar ICH more often located in the superficial than in the deep layers of the cortex, and in non-lobar ICH more often in the deeper layers. We found a tendency towards more severe CAA scores in lobar ICH patients. Other histopathological characteristics were comparable between lobar and non-lobar ICH patients. Although CMIs and CMBs were found in different segments of the cortex in lobar ICH compared to non-lobar ICH patients, otherwise similar histopathological features of cortical CMIs and CMBs distant from the ICH suggest shared pathophysiological mechanisms in lobar and non-lobar ICH caused by different vasculopathies.
Topics: Humans; Cerebral Hemorrhage; Brain; Magnetic Resonance Imaging; Cerebral Amyloid Angiopathy
PubMed: 35384634
DOI: 10.1007/s12975-022-01016-5