Neural Injuries Induced by Hydrostatic Pressure Associated With Mass Effect after Intracerebral Hemorrhage.
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ABSTRACT:
SUBMITTER: Guo T
PROVIDER: S-EPMC6003942 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Intracerebral hemorrhage remains a challenging worldwide clinical problem with no proven treatments. In the acute phase of the illness, there has been some controversy regarding the appropriate management of elevated blood pressure. Recently published and ongoing clinical trials are beginning to shed some light on appropriate blood pressure management in acute intracerebral hemorrhage. This brief review focuses on these trials. In the next few years, it is hoped that clinical uncertainty regarding this issue will be obviated after completion of these trials.
| S-EPMC2981178 | biostudies-other
Project description:BackgroundThe neuroprotective effects of neuroserpin (NSP) have been well documented in both patients and animal models with cerebral ischemia; however, have never been investigated in hemorrhagic stroke. The aim of this study is to verify the neuroprotection of NSP in the non-tPA-induced intracerebral hemorrhage (ICH) mouse model.MethodsC57BL/6J male mice (n = 198) were involved in this study. ICH models were established with infusion of autologous blood into the brain parenchyma. We then detected NSP expression in ICH brains by morphological methods and western blotting analysis. We measured the brain water content and detected blood-brain barrier (BBB) permeability to verify the neuroprotective effects of NSP.ResultsWe found that NSP protein expression was upregulated in ICH models, with a peak at 48 h after ICH induction. NSP local administration reduced the brain edema and the BBB permeability in ICH models. The neurological deficits were also ameliorated. Thus, the neuroprotection of NSP in ICH state was confirmed. Additionally, we also found that the distribution pattern of occludin-expressing cells was obviously changed by the ICH procedure but partly recovered after NSP administration. This finding indicated that protecting and/or repairing the injured vascular endothelial cells may be a potential mechanism involved in NSP neuroprotection, which needs further verification.ConclusionsOur results supported the fact that NSP may be considered as a potential therapy for ICH for the neuroprotective effects including amelioration of the edema.
| S-EPMC5688810 | biostudies-literature
Project description:ObjectivesTo investigate the effects of intensive blood pressure (BP) lowering according to baseline BP levels and optimal achieved BP levels in patients with acute intracerebral hemorrhage (ICH).MethodsINTERACT2 was an open, blinded endpoint, randomized controlled trial in 2,839 patients with ICH within 6 hours of onset and elevated systolic BP (SBP) (150-220 mm Hg) who were allocated to receive intensive (target SBP <140 mm Hg within 1 hour, with lower limit of 130 mm Hg for treatment cessation) or guideline-recommended (target SBP <180 mm Hg) BP-lowering treatment. Outcome was physical function across all 7 levels of the modified Rankin Scale at 90 days.ResultsAnalysis of the randomized comparisons showed that intensive BP lowering produced comparable benefits on physical function at 90 days in 5 subgroups defined by baseline SBP of <160, 160-169, 170-179, 180-189, and ≥190 mm Hg (p homogeneity = 0.790). Analyses of achieved BP showed linear increases in the risk of physical dysfunction for achieved SBP above 130 mm Hg for both hyperacute (1-24 hours) and acute (2-7 days) phases while modest increases were also observed for achieved SBP below 130 mm Hg.ConclusionsIntensive BP lowering appears beneficial across a wide range of baseline SBP levels, and target SBP level of 130-139 mm Hg is likely to provide maximum benefit in acute ICH.Classification of evidenceThis study provides Class I evidence that the effect of intensive BP lowering on physical function is not influenced by baseline BP.
| S-EPMC4336065 | biostudies-literature
Project description:We examined whether hydrostatic-pressure induced nuclear DAF-16 functions as a transcription factor. The expression changes were monitored by using DNA microarray analyses, after the WT adult hermaphrodites were exposed to a pressure of ≥30 MPa for 5 minutes. The results showed significant and reproducible increase of 31 genes after 30 minutes
2020-07-31 | GSE133703 | GEO
Project description:ObjectiveTo assess race-ethnic differences in acute blood pressure (BP) following intracerebral hemorrhage (ICH) and the contribution to disparities in ICH outcome.MethodsBPs in the field (emergency medical services [EMS]), emergency department (ED), and at 24 hours were compared and adjusted for group differences between non-Hispanic black (black), non-Hispanic white (white), and Hispanic participants in the Ethnic Racial Variations of Intracerebral Hemorrhage case-control study. Outcome was obtained by modified Rankin Scale (mRS) score at 3 months. We analyzed race-ethnic differences in good outcome (mRS ≤ 2) and mortality after adjusting for baseline differences and included BP recordings in this model.ResultsOf 2,069 ICH cases enrolled, 30% were white, 37% black, and 33% Hispanic. Black and Hispanic patients had higher EMS and ED systolic and diastolic BPs compared with white patients (p = 0.0001). Although attenuated, at 24 hours after admission, black patients had higher systolic and diastolic BPs. After adjusting for baseline differences, significant race/ethnic differences persisted for EMS systolic, ED systolic and diastolic, and 24-hours diastolic BP. Only ED systolic and diastolic BP was associated with poor functional outcome, and no BP predicted mortality. We found no race-ethnic differences in 3-month functional outcome or mortality after adjusting for group differences, including acute BPs.ConclusionsAlthough black and Hispanic patients had higher BPs than white patients at presentation, we did not find race-ethnic disparities in 3-month functional outcome or mortality. ED systolic and diastolic BP was associated with poor functional outcome, but not mortality, in this race-ethnically diverse population.
| S-EPMC4999322 | biostudies-literature
Project description:Intracerebral hemorrhage (ICH) is a life-threatening condition associated with significant morbidity and mortality. Understanding the molecular mechanisms underlying ICH and its severe form is crucial for developing effective therapeutic strategies. This study investigates transcriptomic alterations in rodent models of ICH and severe intracerebral hemorrhage to shed light on the genetic pathways involved in hemorrhagic brain injury. We performed principal component analysis, revealing distinct principal component segments of normal rats compared to intracerebral hemorrhage and severe intracerebral hemorrhage rats. We further employed heatmaps and volcano plots to identify differentially expressed genes and utilized bar plots and KEGG pathway analysis to elucidate the different molecular pathways involved. Using comprehensive RNA sequencing and bioinformatics analyses, we identified a multitude of differentially expressed genes in both the ICH and severe ICH models. Our results revealed 5679 common genes among the normal, intracerebral hemorrhage, and severe intracerebral hemorrhage groups in the upregulated genes group, and 1196 common genes in the downregulated genes. A volcano plot comparing the groups further highlighted common genes, including PDPN, TIMP1, SERPINE1, TUBB6, and CD44. These findings underscore the complex interplay of genes involved in inflammation, oxidative stress, and neuronal damage. Furthermore, pathway enrichment analysis uncovered key signaling pathways, including the TNF signaling pathway, protein processing in the endoplasmic reticulum, MAPK signaling pathway, and Fc gamma R-mediated phagocytosis, implicated in the pathogenesis of ICH.
2024-06-11 | GSE264394 | GEO
Project description:Differences in the incidence of spontaneous intracerebral hemorrhage (ICH) between ethnicities exist, with an estimated 42% of the variance explained by ethnicity itself. Caucasians have a higher proportion of lobar ICH (LICH, 15.4% of all ICH) than do Asians (3.4%). Alterations in the causal factor exposure between countries justify part of the ethnic variance in ICH incidence. One third of ICH risk can be explained by genetic variation; therefore, genetic differences between populations can partly explain the difference in ICH incidence. In this paper, we review the current knowledge of genetic variants associated with ICH in multiple ethnicities. Candidate gene variants reportedly associated with ICH were involved in the potential pathways of hypertension, vessel wall integrity, lipid metabolism, endothelial dysfunction, inflammation, platelet function, and coagulopathy. Furthermore, variations in APOE (in multiple ethnicities), PMF1/SLC25A44 (in European), ACE (in Asian), MTHFR (in multiple ethnicities), TRHDE (in European), and COL4A2 (in European) were the most convincingly associated with ICH. The majority of the associated genes provide small contributions to ICH risk, with few of them being replicated in multiple ethnicities.
| S-EPMC6321144 | biostudies-literature
Project description:ObjectiveTo assess racial disparities in the prevalence of methamphetamine-associated intracerebral hemorrhage (Meth-ICH) among Native Hawaiians and other Pacific Islanders (NHOPI).MethodsProspectively collected data from an ongoing, multiethnic, single-center cohort study were analyzed. The inclusion criteria for the cohort study required that patients be adult (age 18 years or older) residents of Hawaii with nontraumatic spontaneous intracerebral hemorrhage (ICH). Patients of race other than white, Asian, or NHOPI were excluded. Determination of Meth-ICH was made prospectively by positive urine toxicology result and lack of other clinically suspected ICH etiology. Prevalence of Meth-ICH among NHOPI was compared with that of white and Asian patients.ResultsA total of 193 patients (white 16%, Asian 61%, NHOPI 23%) were analyzed. NHOPI were younger than white (54 ± 15 vs 68 ± 15 years, respectively, p = 0.0001) and Asian (vs 65 ± 16 years, p = 0.0001) patients. Overall, 25 (13%) Meth-ICHs (mean age: 49 ± 6 years, range: 33-56 years) were identified. NHOPI had higher prevalence of Meth-ICH compared with white (24% vs 0%, respectively, p = 0.003) and Asian (vs 12%, p = 0.046) patients. The observed age differences between the racial groups persisted even after excluding the Meth-ICH group (p < 0.01 for all comparison).ConclusionsNHOPI have higher prevalence of Meth-ICH compared with white and Asian patients. However, the age disparity is not entirely driven by methamphetamine abuse.
| S-EPMC4352094 | biostudies-literature
Project description:IMPORTANCE:Intracerebral hemorrhage (ICH) is the most severe form of stroke. Survivors are at high risk of recurrence, death, and worsening functional disability. OBJECTIVE:To investigate the association between blood pressure (BP) after index ICH and risk of recurrent ICH. DESIGN, SETTING, AND PARTICIPANTS:Single-site, tertiary care referral center observational study of 1145 of 2197 consecutive patients with ICH presenting from July 1994 to December 2013. A total of 1145 patients with ICH survived at least 90 days and were followed up through December 2013 (median follow-up of 36.8 months [minimum, 9.8 months]). EXPOSURES:Blood pressure measurements at 3, 6, 9, and 12 months, and every 6 months thereafter, obtained from medical personnel (inpatient hospital or outpatient clinic medical or nursing staff) or via patient self-report. Exposure was characterized in 3 ways: (1) recorded systolic and diastolic measurements; (2) classification as adequate or inadequate BP control based on American Heart Association/American Stroke Association recommendations; and (3) stage of hypertension based on Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure 7 criteria. MAIN OUTCOMES AND MEASURES:Recurrent ICH and its location within the brain (lobar vs nonlobar). RESULTS:There were 102 recurrent ICH events among 505 survivors of lobar ICH and 44 recurrent ICH events among 640 survivors of nonlobar ICH. During follow-up adequate BP control was achieved on at least 1 measurement by 625 patients (54.6% of total [range, 49.2%-58.7%]) and consistently (ie, at all available time points) by 495 patients (43.2% of total [range, 34.5%-51.0%]). The event rate for lobar ICH was 84 per 1000 person-years among patients with inadequate BP control compared with 49 per 1000 person-years among patients with adequate BP control. For nonlobar ICH the event rate was 52 per 1000 person-years with inadequate BP control compared with 27 per 1000 person-years for patients with adequate BP control. In analyses modeling BP control as a time-varying variable, inadequate BP control was associated with higher risk of recurrence of both lobar ICH (hazard ratio [HR], 3.53 [95% CI, 1.65-7.54]) and nonlobar ICH (HR, 4.23 [95% CI, 1.02-17.52]). Systolic BP during follow-up was associated with increased risk of both lobar ICH recurrence (HR, 1.33 per 10-mm Hg increase [95% CI, 1.02-1.76]) and nonlobar ICH recurrence (HR, 1.54 [95% CI, 1.03-2.30]). Diastolic BP was associated with increased risk of nonlobar ICH recurrence (HR, 1.21 per 10-mm Hg increase [95% CI, 1.01-1.47]) but not with lobar ICH recurrence (HR, 1.36 [95% CI, 0.90-2.10]). CONCLUSIONS AND RELEVANCE:In this observational single-center cohort study of ICH survivors, reported BP measurements suggesting inadequate BP control during follow-up were associated with higher risk of both lobar and nonlobar ICH recurrence. These data suggest that randomized clinical trials are needed to address the benefits and risks of stricter BP control in ICH survivors.
| S-EPMC4737594 | biostudies-literature
Project description:OBJECTIVE:To validate various noncontrast CT (NCCT) predictors of hematoma expansion in a large international cohort of ICH patients and investigate whether intensive blood pressure (BP) treatment reduces ICH growth and improves outcome in patients with these markers. METHODS:We analyzed patients enrolled in the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-II) randomized controlled trial. Participants were assigned to intensive (systolic BP <140 mm Hg) vs standard (systolic BP <180 mm Hg) treatment within 4.5 hours from onset. The following NCCT markers were identified: intrahematoma hypodensities, black hole sign, swirl sign, blend sign, heterogeneous hematoma density, and irregular shape. ICH expansion was defined as hematoma growth >33% and unfavorable outcome was defined as modified Rankin Scale score >3 at 90 days. Logistic regression was used to identify predictors of ICH expansion and explore the association between NCCT signs and clinical benefit from intensive BP treatment. RESULTS:A total of 989 patients were included (mean age 62 years, 61.9% male), of whom 186/869 experienced hematoma expansion (21.4%) and 361/952 (37.9%) had unfavorable outcome. NCCT markers independently predicted ICH expansion (all p < 0.01) with overall accuracy ranging from 61% to 78% and good interrater reliability (k > 0.6 for all markers). There was no evidence of an interaction between NCCT markers and benefit from intensive BP reduction (all p for interaction >0.10). CONCLUSIONS:NCCT signs reliably identify ICH patients at high risk of hematoma growth. However, we found no evidence that patients with these markers specifically benefit from intensive BP reduction. CLINICALTRIALSGOV IDENTIFIER:NCT01176565.
| S-EPMC5562954 | biostudies-literature