Pathophysiology Of Intracerebral Hemorrhage Research Articles

Human platelet lysate: a potential therapeutic for intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a major public health challenge worldwide, and is associated with elevated rates of mortality, disability, and morbidity, especially in low- and middle-income nations. However, our knowledge of the detailed molecular processes involved in ICH remains insufficient, particularly those involved in the secondary injury stage, resulting in a lack of effective treatments for ICH. Human platelet lysates (HPL) are abundant in bioactive factors, and numerous studies have demonstrated their beneficial effects on neurological diseases, including their anti-neuroinflammatory ability, anti-oxidant effects, maintenance of blood-brain barrier integrity, and promotion of neurogenesis. In this review, we thoroughly explore the potential of HPL for treating ICH from three critical perspectives: the rationale for selecting HPL as a treatment for ICH, the mechanisms through which HPL contributes to ICH management, and the additional measures necessary for HPL as a treatment for ICH. We elucidate the role of platelets in ICH pathophysiology and highlight the limitations of the current treatment options and advancements in preclinical research on the application of HPL in neurological disorders. Furthermore, historical developments and preparation methods of HPL in the field of biomedicine are discussed. Additionally, we summarize the bioactive molecules present in HPL and their potential therapeutic effects in ICH. Finally, we outline the issues that must be addressed regarding utilizing HPL as a treatment modality for ICH.

Immune Cells and Intracerebral Hemorrhage: A Causal Investigation Through Mendelian Randomization.

The involvement of immune cells in the pathophysiology of intracerebral hemorrhage (ICH) is becoming increasingly recognized, yet their specific causal contributions remain uncertain. The objective of this research is to uncover the potential causal interactions between diverse immune cells and ICH using Mendelian randomization (MR) analysis. Genetic variants associated with 731 immune cell traits were sourced from a comprehensive genome-wide association study (GWAS) involving 3757 participants. Summary statistics data for ICH were acquired from FinnGen, comprising 4056 ICH cases and 371,717 controls. The principal analytical tool utilized in our study was the inverse-variance weighted (IVW) method, incorporated as a key component of a two-sample MR approach. To mitigate potential biases and verify the stability of the conclusions drawn from the primary analytical methods, a series of sensitivity analyses were performed. MR analysis elucidated 33 immune cell traits with causal associations, comprising B cells (eight traits), conventional dendritic cells (cDC, two traits), maturation stages of T cells (two traits), monocytes (two traits), myeloid cells (five traits), TBNK cells (six traits), and regulatory T cells (Treg, eight traits). DP (CD4+CD8+) %T cell (OR=0.83, CI=0.72-0.96, p=0.013) exhibited the strongest protective effect. In contrast, transitional AC (OR=1.09, CI=1.02-1.16, p=0.006) and IgD- CD27- %lymphocyte (OR=1.08, CI=1.00-1.17, p=0.045) showed a higher tendency to increase the ICH risk. The sensitivity analyses validated the robustness and consistency of these results. Our research provides robust evidence substantiating the causal relationship between specific immunophenotypes and ICH risk. The identification of these findings significantly enhances our understanding of the pathogenic mechanisms underlying ICH, particularly pertaining to the immune system. This breakthrough paves the way for innovative clinical and pharmaceutical research opportunities, potentially promoting the development of targeted therapies and enhanced strategies for managing and preventing ICH.

Pathophysiology of Intracerebral Hemorrhage: Recovery Trajectories.

Recovery trajectories in intracerebral hemorrhage (ICH) are recognized as distinct from those observed in ischemic stroke. This narrative review aims to clarify the pathophysiology underlying ICH recovery patterns, highlighting the unique timeline and nature of functional improvements seen in ICH survivors. Population-based cohort studies tracking functional outcomes in a longitudinal fashion, along with randomized clinical trial data with standardized outcome assessments, have demonstrated that ICH recovery generally has a delayed onset in the first weeks, followed by a steep early subacute stage recovery (typically up to 3 months) continuing in protracted, gradual improvements beyond 3 to 6 months. Understanding these recovery patterns, and how these differ from ischemic stroke, is crucial for providing accurate prognostic information, facilitating targeted health care delivery, and optimizing therapeutic interventions and the design of ICH randomized trials. This article synthesizes current evidence on early- and late-stage functional recovery trajectories in primary, spontaneous ICH and cognitive outcomes, emphasizing the clinical and research implications of these recovery patterns.

Recent and future advances in intracerebral hemorrhage

Spontaneous intracerebral hemorrhage (ICH) is defined by the rupture of a cerebral blood vessel and the entry of blood into the brain parenchyma. With a global incidence of around 3.5 million, ICH accounts for almost 30 % of all new strokes worldwide. It is also the deadliest form of acute stroke and survivors are at risk of poor functional outcome. The pathophysiology of ICH is a dynamic process with key stages occurring at successive times: vessel rupture and initial bleeding; hematoma expansion, mechanical mass effect and secondary brain injury (peri-hematomal edema). While deep perforating vasculopathy and cerebral amyloid angiopathy are responsible for 80 % of ICH, a prompt diagnostic work-up, including advanced imaging is require to exclude a treatable cause. ICH is a neurological emergency and simple therapeutic measures such as blood pressure lowering and anticoagulant reversal should be implemented as early as possible as part of a bundle of care. Although ICH is still devoided of specific treatment, recent advances give hope for a cautious optimism. Therapeutic approaches under the scope are focusing on fighting against hemorrhage expansion, promoting hematoma evacuation by minimally invasive surgery, and reducing secondary brain injury. Among survivors, the global vascular risk is now better established, but optimal secondary prevention is still unclear and is based on an individual benefit-risk balance evaluation.

Expression profile of circular RNAs in blood samples of Northern Chinese males with intracerebral hemorrhage shows downregulation of hsa-circ-0090829

Circular RNAs (circRNAs) are involved in several neurological disorders; however, the mechanisms underlying their involvement remain to be clarified. We attempted to explore the expression profiles of circRNAs and their potential functions and mechanisms in the pathogenesis of intracerebral hemorrhage (ICH) in Northern Chinese males. The microarray results showed that 50 circRNAs were significantly upregulated, while 194 circRNAs were significantly downregulated in ICH patients compared with healthy controls (p < 0.05). After bioinformatics analysis, a circRNA–microRNA–messenger RNA network and a protein–protein interaction network were constructed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that the neurotrophin signaling pathway, long-term potentiation, and the mitogen-activated protein kinase pathway are potentially implicated in ICH pathophysiology. The quantitative real-time polymerase chain reaction results revealed that hsa-circ-0090829 was significantly downregulated in ICH. The receiver operating characteristic curve analysis showed that the area under the curve of hsa-circ-0090829 between ICH and healthy controls was 0.807. Furthermore, the dual-luciferase assay showed that hsa-circ-0090829 sponged miR-526b-5p. This study reports the altered expression of circRNAs and identifies the potential functions of these circRNAs in ICH. Our results may facilitate further mechanistic research on circRNAs in ICH and provide probable novel diagnostic biomarkers and therapeutic targets for ICH.

The day after intracerebral hemorrhage: platelet mass index as predictor of survival—a retrospective cohort study

Abstract Background Platelets are implicated in the pathophysiology of intracerebral hemorrhage (ICH). Platelet count (PLT) is affected by platelet loss, while mean platelet volume (MPV) by platelet replenishment. Whether platelet mass index (PMI), the product of PLT and MPV, might predict survival after ICH, remains unknown. Methods All first-ever ICH patients, admitted to Xanthi General Hospital between January 2018 and May 2020 and met eligibility criteria, were enrolled in this retrospective cohort study. Demographics, medical record, first-symptom-to-admission time, vital signs, modified Rankin Scale, ICH score, arterial blood gas test, complete blood count, blood biochemistry, and CT scan test were collected for each patient. PMI values on day 1 (admission; PMI1), day 2 (PMI2), and day 7 (PMI7), along with PLT, MPV, platelet distribution width (PDW), and platelet large cell ratio (P-LCR), were evaluated as potential predictors of 12-month survival using Repeated Measures General Linear Model. Binary discretization of predictors was based on optimal scaling and evaluated using binary regression. Results From 59 patients enrolled (aged 75.7 ± 12.0 years; 31 females), 29 were still alive 12 months after ICH. Age, arterial hypertension, diabetes mellitus, hemoglobin level (Hb), and oxygen saturation (O2Sat) were correlated with 12-month survival. After adjustment for these parameters, PMI1 and PMI2 were independently correlated with 12-month survival (P = 0.048 and P = 0.004, respectively), while PMI7 was not (P = 0.332). PMI2 ≥ 2,400 fL/μL was best to discriminate survivors from non-survivors (age, arterial hypertension, diabetes mellitus, Hb, and O2Sat adjusted OR 0.123 with 95% CI: 0.023–0.694; P = 0.018). Conclusions PMI within the first day after admission for ICH might be used as early predictors of survival. Properly designed prospective studies are needed to further evaluate their contribution as such.

Association between platelet-lymphocyte ratio and 90-day mortality in patients with intracerebral hemorrhage: data from the MIMIC-III database.

Recent evidence suggested that platelet-lymphocyte ratio (PLR) may play a role in the pathophysiology of intracerebral hemorrhage (ICH), but the results are controversial. This study aimed to explore the relationship between PLR and mortality in patients with ICH. All data were extracted from the Medical Information Mart for Intensive Care (MIMIC) III database. The study outcome was 90-day mortality. Multivariable Cox regression analyses were used to calculate the adjusted hazard ratio (HR) with a 95% confidence interval (CI), and curve-fitting (restricted cubic spline) was used to assess the non-linear relationship. Of 1,442 patients, 1,043 patients with ICH were included. The overall 90-day mortality was 29.8% (311/1,043). When PLR was assessed in quartiles, the risk of 90-day mortality for ICH was lowest for quartile 2 (120.9 to <189.8: adjusted HR, 0.67; 95% CI: 0.48-0.93; P = 0.016), compared with those in quartile 1 (<120.9). Consistently in the threshold analysis, for every 1 unit increase in PLR, there was a 0.6% decrease in the risk of 90-day mortality for ICH (adjusted HR, 0.994; 95% CI: 0.988-0.999) in those with PLR <145.54, and a 0.2% increase in 90-day mortality (adjusted HR, 1.002; 95% CI: 1.000-1.003) in participants with PLR ≥145.54. There was a non-linear relationship between PLR and 90-day mortality for patients with ICH, with an inflection point at 145.54 and a minimal risk at 120.9 to <189.8 of PLR.

Bone marrow-mesenchymal stem cells alleviate microglial Pyroptosis after intracerebral hemorrhage in rat by secreting C1q/tumor necrosis factor-related protein 3

BackgroundThere are no specific treatment methods for intracerebral hemorrhage (ICH). Neuroinflammation triggered by microglial pyroptosis plays an important role in ICH pathophysiology. Bone marrow mesenchymal stem cells (BMSCs) are widely used in the treatment of neurological diseases because of their paracrine function. In this study, we aimed to clarify whether BMSCs can alleviate microglial pyroptosis after ICH by secreting C1q/tumor necrosis factor-related protein 3 (CTRP3), a adiponectin paralog with established metabolic regulatory properties and neuroprotective effects. MethodsIn an in vitro study, microglia were stimulated with hemin for pyroptosis and then co-cultured with BMSCs, CTRP3, or CTRP3-small interfering RNA (siRNA)-BMSC; in an in vivo study, intracerebroventricular transplantation of BMSCs or siRNA-CTRP3-BMSCs was performed after ICH surgery. The expression of inflammation-related factors was detected by qRT-PCR and ELISA. Western blotting and immunofluorescence staining were performed to detect the expression of pyroptotic protein, and western blotting was used to detect the activation of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT) and splenic tyrosine kinase (Syk). Behavioral changes were detected 7 days after transplantation. ResultsELISA and qRT-PCR results showed that the production of inflammatory cytokines in hemin-stimulated microglia was significantly downregulated following pretreatment with BMSCs or CTRP3. The Caspase-1 activity assay kit and western blotting results showed that BMSCs attenuated microglial pyroptosis by secreting CTRP3. Furthermore, the modulation functions of BMSCs or CTRP3 involve the promotion of PI3K/AKT and inhibition of Syk signaling pathway activation. Neurological deficits, edema, and disruption of tight junction protein were completely alleviated, while inflammation-related factors and microglial pyroptosis after ICH were significantly downregulated after BMSCs administration. ConclusionBMSCs can inhibit neuroinflammation by inhibiting microglial pyroptosis, thus alleviate ICH symptoms, likely by suppressing the Syk signaling pathway while promoting the PI3K/AKT signaling pathway activation through producing CTRP3.

Intracerebral haemorrhage

Intracerebral haemorrhage (ICH) is a dramatic condition caused by the rupture of a cerebral vessel and the entry of blood into the brain parenchyma. ICH is a major contributor to stroke-related mortality and dependency: only half of patients survive for 1 year after ICH, and patients who survive have sequelae that affect their quality of life. The incidence of ICH has increased in the past few decades with shifts in the underlying vessel disease over time as vascular prevention has improved and use of antithrombotic agents has increased. The pathophysiology of ICH is complex and encompasses mechanical mass effect, haematoma expansion and secondary injury. Identifying the causes of ICH and predicting the vital and functional outcome of patients and their long-term vascular risk have improved in the past decade; however, no specific treatment is available for ICH. ICH remains a medical emergency, with prevention of haematoma expansion as the key therapeutic target. After discharge, secondary prevention and management of vascular risk factors in patients remains challenging and is based on an individual benefit-risk balance evaluation.

Dysregulation of Serum MicroRNA after Intracerebral Hemorrhage in Aged Mice.

Stroke is one of the most common diseases that leads to brain injury and mortality in patients, and intracerebral hemorrhage (ICH) is the most devastating subtype of stroke. Though the prevalence of ICH increases with aging, the effect of aging on the pathophysiology of ICH remains largely understudied. Moreover, there is no effective treatment for ICH. Recent studies have demonstrated the potential of circulating microRNAs as non-invasive diagnostic and prognostic biomarkers in various pathological conditions. While many studies have identified microRNAs that play roles in the pathophysiology of brain injury, few demonstrated their functions and roles after ICH. Given this significant knowledge gap, the present study aims to identify microRNAs that could serve as potential biomarkers of ICH in the elderly. To this end, sham or ICH was induced in aged C57BL/6 mice (18-24 months), and 24 h post-ICH, serum microRNAs were isolated, and expressions were analyzed. We identified 28 significantly dysregulated microRNAs between ICH and sham groups, suggesting their potential to serve as blood biomarkers of acute ICH. Among those microRNAs, based on the current literature, miR-124-3p, miR-137-5p, miR-138-5p, miR-219a-2-3p, miR-135a-5p, miR-541-5p, and miR-770-3p may serve as the most promising blood biomarker candidates of ICH, warranting further investigation.

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.

Expression of DEspR in acute intracerebral hemorrhage

ObjectivesNeuroinflammation and secondary injury play a central role in the pathophysiology of intracerebral hemorrhage. The dual endothelin-1/VEGFsignal-peptide receptor (DEspR) has been reported to mediate the inflammatory response after acute brain injury in a rodent model. We performed a pilot study to assess the expression of DEspR on circulating leukocytes in patients who presented with spontaneous intracerebral hemorrhage (ICH). Materials and methodsWe performed a prospective observational study of patients presenting to two academic medical centers with ICH. Normal healthy volunteers (NHV) were also recruited for sample analysis. Whole blood was obtained, and flow cytometry was performed to examine DEspR expression on neutrophils, monocytes, and lymphocytes. ResultsA total of 19 patients were included in analysis. Median ICH volume was 39 cm3 [IQR 19 cm3, 73 cm3] and median ICH score was 2 [IQR 2, 3]. DEspR expression was more abundant on neutrophils (median 2.4% [IQR 0.5%, 5.8%], p = 0.0064) and monocytes (median 4.4% [IQR 1.7%, 15.8%], p = 0.003) relative to lymphocytes (median 0.9% [IQR 0.2%, 3.3%]). ICH patients had higher DEspR expression in all leukocytes relative to NHV (p < 0.05 for all). Among ICH patients, those with a medical history of hypertension showed higher DEspR expression on neutrophils and monocytes (p = 0.018) compared to those without hypertension. ConclusionsIn this pilot study, DEspR is expressed on circulating neutrophils and monocytes in humans after ICH, with higher levels of expression in those with hypertension. Future work in larger cohorts should examine the relationship of DEspR expression with neuroinflammatory endpoints and long-term outcome.

Biological Aging for Risk Prediction of First-Ever Intracerebral Hemorrhage and Cerebral Infarction in Advanced Age

Background and objectivessuccessful interventions to prevent cerebrovascular disease and stroke require early identification of persons at risk before clinical manifestation of disease. The literature remains to be sparse on accessible plasma-based biomarkers for monitoring brain health and cerebrovascular disease in advanced age. We assessed the predictive value of biological age (BA) as an early indicator for cerebrovascular disease and risk of first-ever intracerebral hemorrhage (ICH) and cerebral infarction (CI) in advanced age and compared these relationships with chronological age (CA) and commonly used biomarkers including tau and Aβ40 and Aβ42. MethodsThe study included Individuals who consented for blood draw and follow-up. We computed biological age using structural equation modelling. The criteria for the biomarkers included their representability of the various body systems; their availability in the Rotterdam study and their pre-hypothesized reflection of aging in other populations. The algorithm integrates biomarkers that represent six body systems involved in overall cerebrovascular health including metabolic function, cardiac function, lung function, kidney function, liver function, immunity, and inflammation. Time to event analysis was conducted using Cox-regression models. Prediction analysis was conducted using Harrel's C and Area under the receiver operating characteristic curve. ResultsThe sample included a total of 1699 individuals at baseline followed up over a median of 11 years. During a period of 15, 780 and 16, 172 person-years, a total of 17 first-ever intracerebral hemorrhage and 83 cerebral infarction cases occurred. In time-to-event analysis, BA showed higher magnitude of associations with ICH compared to CA (HRBA-ICH: 2.30, 95% CI: 1.20, 4.30; HRCA-ICH: 1.40, 95% CI: 0.76, 2.53) and higher precision with CI (HRBA-CI: 1.30, 95% CI: 1.01,1.75; HRCA-CI:1.90, 95% CI: 1.48, 2.66). BA outperformed CA for prediction of ICH (AUC: 0.68 vs 0.53; Harrel's C: 0.72 vs 0.53) and for CI (AUC:0.63 vs 0.62; Harrel's C: 0.68 vs 0.67). ConclusionsBiological aging (delta biological aging) based on integrated physiology biomarkers provides a novel tool for monitoring and identification of persons at highest risk of cerebrovascular disease in advanced age with varying degrees of precision and magnitude for stroke subtypes. These variations are likely related to differences in pathophysiology of intracerebral hemorrhage and cerebral infarction. Wider validation and applicability require extension of these findings in other comparable samples and in clinical settings.

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.

Genetics and Epigenetics of Spontaneous Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a complex and heterogeneous disease, and there is no effective treatment. Spontaneous ICH represents the final manifestation of different types of cerebral small vessel disease, usually categorized as: lobar (mostly related to cerebral amyloid angiopathy) and nonlobar (hypertension-related vasculopathy) ICH. Accurate phenotyping aims to reflect these biological differences in the underlying mechanisms and has been demonstrated to be crucial to the success of genetic studies in this field. This review summarizes how current knowledge on genetics and epigenetics of this devastating stroke subtype are contributing to improve the understanding of ICH pathophysiology and their potential role in developing therapeutic strategies.

413 ABO Blood Type and Thromboembolic Complications After Intracerebral Hemorrhage

INTRODUCTION: Thromboembolic complications (TECs) are preventable causes of morbidity and mortality in patients with intracerebral hemorrhage (ICH). METHODS: Consecutive adult ICH patients enrolled in the Intracerebral Hemorrhage Outcomes Project with available ABO blood type data were included. The primary analysis dichotomized patients by O blood type status (O versus non-O cohorts). The primary outcome was TEC, comprising pulmonary embolism, deep venous thrombosis, ischemic stroke, and myocardial infarction, during the hospital stay. Outcomes were compared between cohorts using multivariable regression and propensity score-matched analyses. A secondary analysis compared outcomes between individual non-type O (i.e., A, B, and AB) and type O blood phenotypes. RESULTS: Type O and non-type O cohorts comprised 269 and 244 patients, respectively. TECs were more common in the type O cohort compared to non-type O cohort (15.2% vs. 9.4%; OR = 1.728 [1.004-2.974], p = 0.048). In the propensity score-matched analysis, comprising 126 patients in each cohort, TEC rates were comparable between the two matched cohorts (13.5% vs. 11.1%; OR = 1.248 [0.586-2.654], p = 0.566). TEC rates were also comparable between individual non-type O and type O blood phenotypes in the secondary analysis. Type A blood phenotype was associated with a lower modified Rankin Scale score at 90 days in shift analysis (OR = 0.654 [0.434-0.985], p = 0.042). CONCLUSION: ABO blood phenotype does not appear to be associated with TECs after spontaneous ICH. Type A blood phenotype may be associated with a better 90-day functional outcomes after ICH. A multicenter, multiethnic ICH study capturing genetic and molecular patient data may help elucidate the potential role of blood phenotype in ICH pathophysiology.

Maximizing Brain Health After Hemorrhagic Stroke: Bugher Foundation Centers of Excellence.

Maximizing Brain Health After Hemorrhagic Stroke: Bugher Foundation Centers of Excellence.

Abstract WP137: Mirna 206 Expression Is Associated With Perihematomal Edema Volume And Functional Outcomes After Intracerebral Hemorrhage

Introduction: Circulating micro-RNAs (miR) are reported in the pathophysiology of intracerebral hemorrhage. Previous reports suggested that miR-206, miR-486, miR-150 and miR-146a are associated with ICH outcomes. In this, study we explored the associated of miRNA expression with radiological predictors of outcome hematoma expansion (HE) and perihematomal edema volume (PHEV) and functional outcomes. Methods: Patients (n=96) with acute spontaneous ICH were consented and blood samples were collected within 48 hours of ICH onset. Plasma miR were used to screen 752 well-characterized miR using locked nucleic acid (LNA) probe-based real-time PCR (ver3.3.5). Cycle threshold data were obtained using the regression method and global mean normalization to a universally expressed miR-92a was applied. Significance levels were assessed using the Mann-Whitney’s U-test and the Welch’s t-test (GenEx). Demographic, clinical data and Modified Rankin Score (MRS) were collected with follow-up calls at 30, 90, and 365-days from ICH onset. Hematoma and perihematomal edema volumes were calculated based on the ABC/2 formula at presentation, 24hrs, and 96hrs from ICH onset. Spearman’s rank correlation was used to determine the association of miRNA expression with HE (&gt;30% increase in volume) and PHEV at onset, 24hrs and 96hrs. Simple logistic regression was used to determine the odds of survival at 30-days and favorable outcome at 90- and 365-days, defined as MRS &lt; 3. Results: Overall, cohort mean age 60.2years (IQR 52-73), 57.1% were deep nuclei (thalamic and basal ganglia ICH), mean ICH vol. 38.4 (SD23.2). We observed a positive correlation with miR-206 and PHEV at 48-96hrs (rho 0.451, p=0.003). Expression of miR-206 was associated with a higher odds of survival at 30-days (OR 1.149 95% CI 1.016-1.299 p=0.0266) and a favorable outcome at 365-days (OR 1.135 95% CI 1.007-1.278 p=0.038). There was no association of miR-206 expression with HE. miR-486, miR-150, and miR-146a were not associated with radiological or functional outcomes. Conclusion: In our cohort, miR-206 was associated with PHEV at 96hrs, survival at 30days and favorable outcome at 1 year. Further studies are ongoing to further delineate the role of miR206 in ICH related biological mechanisms.

Abstract WP256: Favorable Outcome In Intracerebral Hemorrhage Is Associated With With Higher 15-lox-1 Expression

Background: In previous studies, we identified a higher abundance of the docosanoid, Neuroprotectin D1 (NPD1), a lipid anti-inflammatory mediator, in intracerebral hemorrhage (ICH) patients with favorable outcome. In this study, we hypothesized that favorable outcome is due to increased expression of 15-LOX-1, a critical enzyme in the endogenous synthesis of NPD1 compared with patients with unfavorable outcome. Methods: After informed consent, whole blood were collected in PaxGene blood RNA tubes from consecutive patients with acute spontaneous ICH within 48 hours of admission. Total RNA was used for real-time PCR using Taqman probe for 15-LOX-1. The PCR cycle threshold (Ct) of 15-LOX-1 was normalized to the endogenous control GAPDH and fold change determined. Demographic and clinical data were collected. Outcome measures included 90-day modified Rankin score. In this study favorable outcome is defined as MRS 0-3 (n=11) and unfavorable outcome as MRS 4-6 (n=25). Results: Thirty-six patients were included in the study with a mean age of 61.9 years (SD 13.1). In patients with favorable outcome, the mean normalized Ct for 15-LOX-1 was 3.5 (SD 1.8) while in unfavorable was 8.9 (SD 3.8), and for normal healthy was 1.4 (SD 0.4). Expression of 15-LOX-1 was 43-fold higher in patients with favorable outcome. Conclusion: The increased expression of 15-LOX-1 suggests a significant synthesis and abundance of NPD1 in patients with MRS 0-3 compared with patients with MRS 4-6 and suggests that early synthesis and abundance of NPD1 is likely an important protective mediator in ICH pathophysiology

Neuroprotectin D1, a lipid anti-inflammatory mediator, in patients with intracerebral hemorrhage

Little is known of the lipid anti-inflammatory mediators, docosanoids, in intracerebral hemorrhage (ICH). We aim to characterize the abundance of the docosanoid, Neuroprotectin D1 (NPD1), in ICH patients.Blood samples (whole blood in PAXgene-blood-RNA tubes and plasma) were collected from consecutive patients with acute spontaneous ICH within 48 h of admission. A liquid-liquid lipid extraction was used for liquid chromatography-mass spectrometry (LC-MS/MS) and analyzed using MassLynx Mass Spectrometry Software with results normalized to internal standards. RNA was extracted from PAXgene-blood-RNA tubes for 15-LOX-1 gene expression, a critical enzyme in NPD1 synthesis. Demographic and clinical data were collected. Outcome measures included 90-day modified-rankin-score.Sixteen patients were included in the study with a mean age of 62.5years (SD13.5). Three abundant isomers were detected and analyzed – NPD1, PDX, and an uncharacterized isomer designated as NPD1-C. NPD1 levels were higher in patients with 90-day MRS 0–3 (49.63pg/mL SD43.78 vs. 1.88pg/mL SD1.7 p = 0.0012). ROC-AUC analysis showed an NPD1 cutoff of 2.9pg/mL differentiated 90-day MRS 0–3 (sensitivity 100%, specificity 88.89%, AUC 0.98 p = 0.0002). A Spearman correlation demonstrated an inverse relationship with NPD1 and 90-day MRS (rho −7.392 p = 0.0011). 15-LOX-1 gene was almost undetectable in patients with MRS 4–6. Though not significant, NPD1 levels were higher in patients <65 years, ICH volume <30 ml, and non-whites. NPD1 was abundant and significantly higher in ICH patients with MRS 0–3.15-LOX-1 was significantly under-expressed in patients with MRS 4–6. Early synthesis and abundance of NPD1 is likely an important protective mediator in ICH pathophysiology.