Therapies For Intracerebral Hemorrhage Research Articles

MicroRNAs modulate neuroinflammation after intracerebral hemorrhage: Prospects for new therapy.

Intracerebral hemorrhage (ICH) is the most common subtype of hemorrhagic stroke. After ICH, blood components extravasate from vessels into the brain, activating immune cells and causing them to release a series of inflammatory mediators. Immune cells, together with inflammatory mediators, lead to neuroinflammation in the perihematomal region and the whole brain, and neuroinflammation is closely related to secondary brain injury as well as functional recovery of the brain. Despite recent progress in understanding the pathophysiology of ICH, there is still no effective treatment for this disease. MicroRNAs (miRNAs) are non-coding RNAs 17-25 nucleotides in length that are generated naturally in the human body. They bind complementarily to messenger RNAs and suppress translation, thus regulating gene expression at the post-transcriptional level. They have been found to regulate the pathophysiological process of ICH, particularly the neuroinflammatory cascade. Multiple preclinical studies have shown that manipulating the expression and activity of miRNAs can modulate immune cell activities, influence neuroinflammatory responses, and ultimately affect neurological functions after ICH. This implicates the potentially crucial roles of miRNAs in post-ICH neuroinflammation and indicates the possibility of applying miRNA-based therapeutics for this disease. Thus, this review aims to address the pathophysiological roles and molecular underpinnings of miRNAs in the regulation of neuroinflammation after ICH. With a more sophisticated understanding of ICH and miRNAs, it is possible to translate these findings into new pharmacological therapies for ICH.

In vitro models of intracerebral hemorrhage

Intracerebral hemorrhage (ICH) is a severe clinical emergency caused by bleeding into brain parenchyma. Currently, there are no effective treatments to improve ICH outcomes. Developing new therapies for ICH relies on a thorough understanding of ICH pathophysiology and good in vitro models that enable mechanistic research. In this review, we summarize commonly used in vitro ICH models and compare their advantages and disadvantages. Next, key questions that need to be answered in future research are discussed. We aim to provide a quick reference/summary of widely used in vitro ICH models and stimulate the development of new models.

Abstract 258: Prehospital Transport Protocol For Comprehensive Stroke Center Triage Is Associated With Reduced Last KnownWell To Arrival Times For Intracranial Hemorrhage

Title: Prehospital Transport Protocol for Comprehensive Stroke Center Triage is Associated with Reduced Last Known Well to Arrival Times for Intracranial Hemorrhage Background: In September 2018, we implemented a prehospital routing protocol for patients with suspected severe stroke and large vessel occlusion using the 3 Item Stroke Scale (3I-SS). Patients who have a 3I-SS score of ≥4 and have a known last normal time of ≤6 hours were transported to the closest Comprehensive Stroke Center (CSC). While the impact on endovascular treatment for ischemic stroke is more established, the effect of this transport policy on patients with intracerebral hemorrhage (ICH) is unknown. Objective/Methods: The objective of the study was to determine if implementation of a regional CSC transport protocol reduced last known well (LKW) to hospital arrival time for patients with ICH. Data was retrospectively reviewed all patients with a primary diagnosis of ICH from Get With The Guidelines®(GWTG) Stroke regional registry between January 2018 to May 2019 (8 month pre and 8 months post-implementation) and consisting of 16 Primary Stroke Centers (PSCs) and 8 CSCs. We analyzed LKW-arrival times to compare median times in the pre- vs. post-implementation periods. Results: There were 501 ICH cases in the pre-implementation period (mean age 66, 43.3% Black, and 52.3% male) and 548 in the post-implementation period (mean age 66, 41.0% Black, and 54.3% male). In the post-implementation period, median LKW to hospital arrival time was 255 minutes vs. 270.5minutes in the pre-implementation period (P value 0.029). LKW to hospital arrival times for those patients arriving from EMS decreased from a median 112.5 minutes to 81 minutes (P value 0.034). Conclusions: A prehospital direct-to-CSC transport protocol resulted in a substantial decrease in the median LKW to hospital arrival times for ICH patients, driven especially by EMS-arriving patients. Prehospital protocols could increase access to time sensitive life-saving therapies for ICH.

Hyperacute transplantation of umbilical cord mesenchymal stromal cells in a model of severe intracerebral hemorrhage.

Aim:Intracerebral hemorrhage (ICH) has limited therapeutic options. We have shown that an intravenous injection of human umbilical cord-derived mesenchymal stromal cells (hUC-MSC) 24 h after an ICH in rats reduced the residual hematoma volume after a moderate hemorrhage but was inefficient in severe ICH. Here, we investigated whether a treatment in the hyperacute phase would be more effective in severe ICH.Materials & methods:Wistar rats were randomly selected to receive an intravenous injection of hUC-MSC or the vehicle 1 h after a severe ICH.Results:The hyperacute treatment with hUC-MSC did not affect the 22-day survival rate, the motor function or the residual hematoma volume.Conclusion:These results indicate the need for optimization of hUC-MSC-based therapies for severe ICH.

Abstract TP135: Prehospital Transport Protocol For Comprehensive Stroke Center Triage Is Associated With Reduced Last Known Well To Arrival Times For Intracranial Hemorrhage

Background: In September 2018, we implemented a prehospital routing protocol for patients with suspected severe stroke and large vessel occlusion using the 3 Item Stroke Scale (3I-SS). Patients who have a 3I-SS score of ≥4 and have a known last normal time of ≤6 hours were transported to the closest Comprehensive Stroke Center (CSC). While the impact on endovascular treatment for ischemic stroke is more established, the effect of this transport policy on patients with intracerebral hemorrhage (ICH) is unknown. Objective/Methods: The objective of the study was to determine if implementation of a regional CSC transport protocol reduced last known well (LKW) to hospital arrival time for patients with ICH.Data was retrospectively reviewed all patients with a primary diagnosis of ICH from Get With The Guidelines® (GWTG) Stroke regional registry between January 2018 to May 2019 (8 month pre and 8 months post-implementation) and consisting of 16 Primary Stroke Centers (PSCs) and 8 CSCs. We analyzed LKW-arrival times to compare median times in the pre- vs. post-implementation periods. Results: There were 501 ICH cases in the pre-implementation period (mean age 66, 43.3% Black, and 52.3% male) and 548 in the post-implementation period (mean age 66, 41.0% Black, and 54.3% male). In the post-implementation period, median LKW to hospital arrival time was 255 minutes vs. 270.5 minutes in the pre-implementation period (P value 0.029). LKW to hospital arrival times for those patients arriving from EMS decreased from a median 112.5 minutes to 81 minutes (P value 0.034). Conclusions: A prehospital direct-to-CSC transport protocol resulted in a substantial decrease in the median LKW to hospital arrival times for ICH patients, driven especially by EMS-arriving patients. Prehospital protocols could increase access to time sensitive life-saving therapies for ICH.

Neuroprotective Therapies for Spontaneous Intracerebral Hemorrhage.

Patients who survive the initial ictus of spontaneous intracerebral hemorrhage (ICH) remain vulnerable to subsequent injury of the perilesional parenchyma by molecular and cellular responses to the hematoma. Secondary brain injury after ICH, which contributes to long-term functional impairment and mortality, has emerged as an attractive therapeutic target. This review summarizes preclinical and clinical evidence for neuroprotective therapies targeting secondary injury pathways following ICH. A focus on therapies with pleiotropic antiinflammatory effects that target thrombin-mediated chemotaxis and inflammatory cell migration has led to studies investigating statins, anticholinergics, sphingosine-1-phosphate receptor modulators, peroxisome proliferator activated receptor gamma agonists, and magnesium. Attempts to modulate ICH-induced blood-brain barrier breakdown and perihematomal edema formation has prompted studies of nonsteroidal antiinflammatory agents, matrix metalloproteinase inhibitors, and complement inhibitors. Iron chelators, such as deferoxamine and albumin, have been used to reduce the free radical injury that ensues from erythrocyte lysis. Stem cell transplantation has been assessed for its potential to enhance subacute neurogenesis and functional recovery. Despite promising preclinical results of numerous agents, their outcomes have not yet translated into positive clinical trials in patients with ICH. Further studies are necessary to improve our understanding of the molecular events that promote damage and inflammation of the perihematomal parenchyma after ICH. Elucidating the temporal and pathophysiologic features of this secondary brain injury could enhance the clinical efficacy of neuroprotective therapies for ICH.

Short- and Long-term Health Care Resource Utilization and Costs Following Intracerebral Hemorrhage.

We sought to evaluate the short- and long-term resource use and costs associated with intracerebral hemorrhage (ICH) taken from an entire population. We in addition sought to evaluate the association of oral anticoagulation (OAC) and health care costs. This was a retrospective cohort study of adult patients (≥18 years) with ICH in the entire population of Ontario, Canada (2009-2017). We captured outcomes through linkage to health administrative databases. We used generalized linear models to identify factors associated with total cost. Analysis of OAC use was limited to patients ≥66 years of age. The primary outcome was total 1-year direct health care costs in 2020 US dollars. Among 16,248 individuals with ICH (mean age 71.2 years, male 52.3%), 1-year mortality was 46.0%, and 24.2% required mechanical ventilation. The median total 1-year cost was $26,886 (interquartile range [IQR] $9,641-$62,907) with costs for those who died in hospital of $7,268 (IQR $4,031-$14,966) vs $44,969 (IQR $20,264-$82,414, p < 0.001) for survivors to discharge. OAC use (analysis limited to individuals ≥66 years old) was associated with higher total 1-year costs (cost ratio 1.06 [95% confidence interval 1.01-1.11]). Total 1-year costs for the entire cohort exceeded $120 million per year over the study period. ICH is associated with significant health care costs, and the median cost of a patient with ICH is roughly 10 times the median inpatient cost in Ontario. Costs were higher among survivors than deceased patients. OAC use is independently associated with increased costs. To maximize cost-effectiveness, future therapies for ICH must aim to reduce disability, not only improve mortality.

L-3-n-butylphthalide promotes restoration after an experimental animal model of intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a devastating type of stroke with high morbidity and mortality, and the effective therapies for ICH remain to be explored. L-3-n-butylphthalide (NBP) is widely used in the treatment of ischemic stroke. However, few studies evaluated the therapeutic effects of NBP on ICH. Therefore, the present study aims to evaluate the effects of NBP on ICH and its potential mechanism. The rats were randomly divided into sham-operated group, saline-treated (ICH + saline) group, and NBP-treated (ICH + NBP) group. The ICH model of SD rats induced by IV collagenase was established. The modified Garcia JH score was used to detect the neurological deficit in rats. Western Blot and immunohistochemistry analysis was applied to test the levels of UBIAD1 and caspase-3 expressions in the perihematomal region. The rates of apoptotic cells were detected by TUNEL staining. The results showed that NBP up-regulated the expression of UBIAD1, reduced the apoptotic cells in the perihematomal region, and improved the neurological deficit. Taken together, our study added some new evidence to the application of NBP in ICH treatment.

Exosomes Derived from MicroRNA-146a-5p-Enriched Bone Marrow Mesenchymal Stem Cells Alleviate Intracerebral Hemorrhage by Inhibiting Neuronal Apoptosis and Microglial M1 Polarization.

IntroductionIntracerebral hemorrhage (ICH) is a devastating type of stroke with high mortality, and the effective therapies for ICH remain to be explored. Exosomes (Exos) have been found to play important roles in cell communication by transferring molecules, including microRNAs (miRNAs/miRs). MiRNAs are critical regulators of genes involved in many various biological processes and have been demonstrated to aggravate or alleviate brain damages induced by ICH. The aim of the present study was to investigate the effect of Exos derived from miR-146a-5p-enriched bone marrow mesenchymal stem cells (BMSCs-miR-146a-5p-Exos) on experimental ICH.MethodsICH was induced in adult male Sprague-Dawley rats by an intrastriatal injection of collagenase type IV. At 24 h after surgery, Exos were administrated. For detecting apoptotic cells, TUNEL staining was performed using an in situ Cell Death Detection Kit. Fluoro-Jade B staining was performed to detect degenerating neurons. Immunofluorescence assay was performed to detect the expression of myeloperoxidase (MPO) and OX-42. The binding of miR-146a-5p and its target genes was confirmed by luciferase reporter assay.ResultsAt 24 h after surgery, BMSCs-miR-146a-5p-Exos administration significantly improved neurological function, reduced apoptotic and degenerative neurons, and inhibited inflammatory response. Furthermore, miR-146a-5p-enriched Exos obviously inhibited the M1 polarization of microglia after ICH in rats, accompanied by the reduced expression of pro-inflammatory mediators releasing by M1 microglia including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and monocyte chemoattractant protein-1 (MCP-1). Finally, we observed that miR-146a-5p directly targeted interleukin-1 receptor-associated kinase1 (IRAK1) and nuclear factor of activated T cells 5 (NFAT5), which contributed to the inflammation response and the polarization of M1 microglia/macrophages.ConclusionWe demonstrated that miR-146a-5p-riched BMSCs-Exos could offer neuroprotection and functional improvements after ICH through reducing neuronal apoptosis, and inflammation associated with the inhibition of microglial M1 polarization by downregulating the expression of IRAK1 and NFAT5.

Beneficial Role of Neutrophils Through Function of Lactoferrin After Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a devastating disease with a 30-day mortality of ~50%. There are no effective therapies for ICH. ICH results in brain damage in 2 major ways: through the mechanical forces of extravasated blood and then through toxicity of the intraparenchymal blood components including hemoglobin/iron. LTF (lactoferrin) is an iron-binding protein, uniquely abundant in polymorphonuclear neutrophils (PMNs). After ICH, circulating blood PMNs enter the ICH-afflicted brain where they release LTF. By virtue of sequestrating iron, LTF may contribute to hematoma detoxification. ICH in mice was produced using intrastriatal autologous blood injection. PMNs were depleted with intraperitoneal administration of anti-Ly-6G antibody. Treatment of mouse brain cell cultures with lysed RBC or iron was used as in vitro model of ICH. LTF mRNA was undetectable in the mouse brain, even after ICH. Unlike mRNA, LTF protein increased in ICH-affected hemispheres by 6 hours, peaked at 24 to 72 hours, and remained elevated for at least a week after ICH. At the single cell level, LTF was detected in PMNs in the hematoma-affected brain at all time points after ICH. We also found elevated LTF in the plasma after ICH, with a temporal profile similar to LTF changes in the brain. Importantly, mrLTF (recombinant mouse LTF) reduced the cytotoxicity of lysed RBC and FeCl3 to brain cells in culture. Ultimately, in an ICH model, systemic administration of mrLTF (at 3, 24, and 48 hours after ICH) reduced brain edema and ameliorated neurological deficits caused by ICH. mrLTF retained the benefit in reducing behavioral deficit even with 24-hour treatment delay. Interestingly, systemic depletion of PMNs at 24 hours after ICH worsened neurological deficits, suggesting that PMN infiltration into the brain at later stages after ICH could be a beneficial response. LTF delivered to the ICH-affected brain by infiltrating PMNs may assist in hematoma detoxification and represent a powerful potential target for the treatment of ICH.

Stem Cell Therapies for Intracerebral Hemorrhages.

An insult due to intracerebral hemorrhage (ICH) is critical to patients. So, breakthroughs in ICH treatment are very important. Advances in the stem cell treatment of stroke have been remarkable. And stem cell experimentation on ischemic stroke, however, preceded such work on ICH and did not emphasized ICH therapy. We review recent stem cell treatments for ICH, an experimental model of ICH, the medical care of ICH, and several stem cell therapies for ICH along with future prospects. Stem cell therapy for ICH is effective in rodent or animal models. For humans, only a small number of clinical trials have been done, and significant functional recovery was recorded. We need to reveal the mechanism of stem cell therapy and develop a reliable, definitive treatment strategy for treatment of ICH. In the future, several types of stem cells will be available for the treatment of ICH.

Abstract 213: Hematoma-infiltrating Macrophages Transition From Inflammatory to Reparative Programs in Patients After Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) causes rapid recruitment of circulating leukocytes to the injury; however, the roles of these cells in disease progression and repair in the brain are poorly understood. Findings from animal models have failed to translate into effective therapies for ICH, emphasizing the importance of studying the ICH immune response in the patient population. To gain insight into the inflammatory response in patient hematomas, we are utilizing mass cytometry, flow cytometry, and RNA-seq to characterize hematoma-infiltrating leukocytes isolated from ICH patients over a 5 day period, in conjunction with the ongoing MISTIE III trial for surgical evacuation of ICH. We have found that the hematoma immune infiltrate is predominantly composed of neutrophils and macrophages recruited from the circulation, rather than CNS-resident microglia. We have observed that hematoma macrophages have acquired a distinct phenotype differing from phagocyte populations in the peripheral blood, suggesting that their gene expression is controlled by local signals in the hematoma. Preliminary transcriptional analysis of hematoma macrophages 24-50 hours post-ICH has revealed an inflammatory profile characterized by increased expression of antigen presentation, TLR signaling, glycolytic metabolism, and prostaglandin production pathways (Figure 1). Intriguingly, by 100 hours post-ICH, macrophages downregulated these pathways and engaged a wound healing program characterized by TGF-beta signaling, fatty acid metabolism, and collagen deposition (Figure 1). These findings, in agreement with our previous results in animal models of ICH, suggest that recruited macrophages may contribute not only to initial inflammatory damage, but also to clearance of the hematoma and resolution of inflammation, making them potentially ideal targets for therapeutic intervention.

Intracerebral Hemorrhage as an Axonal Tract Injury Disorder with Inflammatory Reactions.

Intracerebral hemorrhage (ICH) is a neurological disorder frequently accompanied by severe dysfunction. Critical pathogenic events leading to poor prognosis should be identified for the development of novel effective therapies for ICH. Here we focus on the injury of the axonal tract, particularly of the internal capsule, with reference to its contribution to ICH pathology and potential therapeutic interventions in addition to its cellular mechanisms. Studies on human ICH patients and rodent models of ICH suggest that invasion of hematoma into the internal capsule greatly worsens the severity of post-ICH symptoms. A blood-derived protease thrombin may play an important role in the acute phase of axonal tract injury in the internal capsule that includes compromised axonal transport and fragmentation of axonal structures. Several agents such as clioquinol, melatonin and Am80 (a retinoic acid receptor agonist) have been shown to produce therapeutic effects on rodent models of ICH associated with injury of the internal capsule. In the course of examinations on the effect of Am80, we obtained evidence for the involvement of CXCL2, a neutrophil chemotactic factor, in the pathogenesis of ICH. Accordingly, we also refer to the potential roles of infiltrating neutrophils and inflammatory responses in axonal tract injury and resultant neurological dysfunction in ICH.

New Avenues for Treatment of Intracranial Hemorrhage

The mortality and morbidity from intracerebral hemorrhage (ICH) remain high despite advances in medical, neurologic, and surgical care during the past decade. The lessons learned from previous therapeutic trials in ICH, improved understanding of the pathophysiology of neuronal injury after ICH, and advances in imaging and pre-hospital assessment technologies provide optimism that more effective therapies for ICH are likely to emerge in the coming years. The potential new avenues for the treatment of ICH include a combination of increased utilization of minimally invasive surgical techniques with or without thrombolytic usage to evacuate or reduce the size of the hematoma; utilization of advanced imaging to improve selection of patients who are likely to benefit from reversal of coagulopathy or hemostatic therapy; ultra-early diagnosis and initiation of therapy in the ambulance; and the use of novel drugs to target the secondary injury mechanisms, including the inflammatory cascade, perihematomal edema reduction, and hemoglobin degradation products-mediated toxicity.

Supratentorial Intracerebral Hemorrhage

Supratentorial intracerebral hemorrhage (ICH) is a devastating condition with high morbidity and mortality. There are currently no proven pharmacological therapies for ICH, and the role of surgery is controversial. In the neurointensive care setting, management currently focuses on optimization of systemic physiology to offer neuroprotection by maintenance of adequate cerebral perfusion and substrate delivery, using targets derived principally from traumatic brain injury. Advances in technology, neuroimaging, and neuromonitoring techniques have significantly improved the detection of neural compromise and our understanding of the pathophysiology of ICH, including the nature of the perihematomal penumbra and role of mitochondrial dysfunction. Here, we review the developments in neuromonitoring and their application to ICH, highlighting the importance of multimodality neuromonitoring to comprehensively assess cerebral perfusion, oxygenation, and metabolic status as well as offer an extended window for the prevention, early detection, and treatment of secondary neuronal injury and complications such as hematoma expansion. Technical advances will likely lead to the development of noninvasive monitors that deliver continuous measurement of cerebral hemodynamics, oxygenation, and metabolism over multiple regions of interest simultaneously. A key future priority will be to provide high-quality robust evidence that multimodality monitoring-guided treatment can lead to improved outcome.

Intensivmedizinische Versorgung von Patienten mit intrazerebraler Blutung

Approximately 10-15% of acute strokes are caused by non-aneurysmatic intracerebral hemorrhage (ICH) and incidences are expected to increase due to an aging population. Studies from the 1990s estimated mortality of ICH to be as high as 50%. However, these figures may partly be attributed to the fact that patients suffering from ICH frequently received only supportive therapy and the poor prognosis may therefore be more a self-fulfilling prophecy. Recently it has been shown that treatment in a specialized neurological intensive care unit alone was associated with better outcomes after ICH. In recent years considerable efforts have been undertaken in order to develop new therapies for ICH and to assess them in randomized controlled trials. Apart from admission status, hemorrhage volume is considered to be the main prognostic factor and impeding the spread of the hematoma is thus a basic therapeutic principle. The use of activated factor VIIa (aFVIIa) to stop hematoma enlargement has been assessed in two large randomized controlled trials, however the promising results of the dose-finding study could not be confirmed in a phase III trial. Although hemostatic therapy with aFVIIa reduced growth of the hematoma it failed to improve clinical outcome. Similar results were found in a randomized controlled trial on blood pressure management in acute ICH. The link between reduction of hematoma growth and improved outcome is therefore still lacking. Likewise the value of surgical hematoma evacuation remains uncertain. In the largest randomized controlled trial on surgical treatment in ICH so far, only a small subgroup of patients with superficial hemorrhages seemed to benefit from hematoma evacuation. Whether improved intensive care can contribute to improved outcome after ICH will be shown by data obtained in the coming years.

Atherosclerotic Peripheral Vascular Disease Symposium II

Stroke is the third leading cause of death and a leading cause of adult disability in the United States.1 From a global perspective, stroke is also a leading cause of death and disability. The past 20 years have seen significant improvements in stroke prevention, yet each year, >700 000 people have a new or recurrent stroke.2,3 The medical and societal costs of stroke exceed $62 billion in the United States alone.4 Any intervention that could reverse or limit the effects of a stroke would have dramatic medical, societal, and public health benefits. This section will focus on treatment of acute ischemic stroke, which accounts for 80% to 85% of all strokes. Other recent publications have focused on therapies for intracerebral hemorrhage. Acute interventions to reduce the effects of an ischemic stroke can be organized into several main approaches: (1) reperfusion strategies (lytics, endovascular/mechanical); (2) neuroprotection; and (3) restoration, regeneration, and rehabilitation. ### Medical Therapies Thrombolytic therapies for acute ischemic stroke have been used or under study for 30 to 40 years, yet only recently has an agent been approved by the US Food and Drug Administration (FDA) and included in the treatment guidelines. Intravenous recombinant tissue plasminogen activator (rtPA) is the only FDA-approved medical therapy proven to reduce the effects of an ischemic stroke.5,6 Its main mechanism of action is to lyse a clot that is occluding a cerebral vessel, thereby reperfusing distal ischemic brain tissue and preventing or limiting the area of cell death and tissue necrosis. The efficacy of intravenous rtPA was proven in the pivotal National Institute of Neurological Disorders and Stroke (NINDS) rtPA study, which showed improved outcomes for patients treated within 3 hours of stroke onset.7 The NINDS tissue plasminogen activator (tPA) trial had an efficacy end point that was equivalent to the …

Current treatment options for intracerebral hemorrhage

Intracerebral hemorrhage (ICH) remains the least treatable form of stroke. Despite ongoing attempts to find effective interventions based on the physiopathologic understanding of this disease, evidence-based medical therapies for ICH are limited to recommendations on blood pressure (BP) reduction, intracranial pressure monitoring, osmotherapy with adequate fluid resuscitation, fever and glycemic control, and seizure prophylaxis. Although the value of surgical treatment remains in doubt because of the negative results of the International Surgical Trial in Intracerebral Haemorrhage (STICH), a subgroup analysis of this study suggested better outcomes among patients with superficial hematomas who underwent surgical evacuation, supporting the ongoing STICH-II trial. Other approaches currently under study include ultra-early hemostatic therapy and BP reduction, thrombolytic therapy for intraventricular hemorrhage, and minimally invasive surgical approaches.

New era for management of primary hypertensive intracerebral hemorrhage

This discussion focuses on recent reports relevant to improved understanding and future directions in the management of intracerebral hemorrhage (ICH). Prevention is possible with adequate treatment of hypertension; microbleeds, apolipoprotein genotype, and cholesterol treatment have been examined in relation to ICH risk. Hematoma products, matrix metalloproteinases, inflammatory markers, and means to attenuate injury have also received attention. The multifaceted character of perihematomal edema has been further defined but evidence for perihematomal ischemia remains elusive. New data on acute blood pressure reinforces the need for a clinical trial. With the lack of efficacy found in the International Surgical Trial in Intracerebral Hemorrhage (ISTICH), a landmark surgical trial, emphasis is shifting to minimally invasive and catheter/thrombolytic-based technologies for clot evacuation. On the medical side, activated factor VII has been shown to control hemorrhage growth. Looking forward, stem cell therapies for ICH are under investigation and some outcome studies are shedding new rays of hope.