Progesterone exerts neuroprotective effects and improves long-term neurologic outcome after intracerebral hemorrhage in middle-aged mice.
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ABSTRACT:
SUBMITTER: Jiang C
PROVIDER: S-EPMC4857017 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Although intracerebral hemorrhage (ICH) volume and location are important predictors of outcome in adults, few data exist in children.A consecutive cohort of children, including full-term newborns to those younger than 18 years of age with nontraumatic, acute ICH and head CT available for analysis were studied. Clinical information was abstracted via chart review. Hemorrhage volume was expressed as percentage of total brain volume (TBV) with large hemorrhage defined as >or=4% of TBV. Hemorrhages were manually traced on each head CT slice and volumes were calculated by multiplying by slice thickness. Location was classified as supratentorial or infratentorial. Logistic regression was used to identify predictors of poor neurological outcome, defined as a Glasgow outcome scale <or=2 (death or persistent vegetative state).Thirty children were included, median age 6 years. Median ICH volume was 20.4 cm(3) and median ICH size as a percentage of TBV was 1.9%. Only 4 of 22 children with ICH <4% of TBV had poor outcomes, vs 5 of 8 children with ICH >or=4% of TBV (P=0.03). In multivariate analysis, hemorrhage >or=4% of TBV (OR, 22.5; 95% CI, 1.4-354; P=0.03) independently predicted poor outcome 30 days after ICH. In this small sample, infratentorial hemorrhage location and the presence of intraventricular hemorrhage did not predict poor outcome.ICH volume predicts neurological outcome at 30 days in children, with worst outcome when hemorrhage is >or=4% of TBV. Location and ICH etiology may also be important. These findings identify children with ICH who are candidates for aggressive management and may influence counseling regarding prognosis.
| S-EPMC2830068 | biostudies-other
Project description:Recent studies have shown that fingolimod (FTY720) is neuroprotective in CNS injury models of cerebral ischemia and spinal cord injury. The purpose of the study was to examine the effect of fingolimod in a mouse model of intracerebral hemorrhage. ICH was produced in adult CD1 mice by injecting collagenase VII-S (0.5 µL, 0.06 U) into the basal ganglia. Fingolimod (or saline) was given 30 min after surgery and once daily for two days. Three days after intracerebral hemorrhage, brain edema, hematoma volume and the number of apoptotic cells were quantified. In another cohort of mice, brain atrophy was evaluated two weeks following intracerebral hemorrhage. Neurobehavioral tests were performed on the 3rd, the 7th and the 14th day. Fingolimod significantly decreased edema, apoptosis and brain atrophy. More importantly, fingolimod enhanced neurobehavioral recovery. Preliminary experiments showed no difference in the number of inflammatory (CD68-positive) cells between the two groups. In conclusion, fingolimod exerts protective effects in a mouse model of intracerebral hemorrhage; the mechanisms underlying these neuroprotective effects deserve further study.
| S-EPMC3994537 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:Intracerebral hemorrhage is a considerable source of morbidity and mortality. This 3-center study describes outcomes of pediatric intracerebral hemorrhage and identifies 2-year neurological outcome predictors. METHODS:Children 29 days to 18 years of age presenting with intracerebral hemorrhage from March 2007 to May 2015 were enrolled prospectively. Exclusion criteria included trauma; intracranial tumor; hemorrhagic transformation of arterial ischemic stroke or cerebral sinovenous thrombosis; isolated subdural, epidural, or subarachnoid hemorrhage; and abnormal baseline neurological function. Intracerebral hemorrhage and total brain volumes were measured on neuroimaging. The Pediatric Stroke Outcome Measure assessed outcomes. RESULTS:Sixty-nine children were included (median age: 9.7 years; interquartile range: 2.2-14). Six children (9%) died during hospitalization. Outcomes in survivors were assessed at early follow-up in 98% (median 3.1 months; interquartile range: 3.1-3.8) and at later follow-up in 94% (median: 2.1 years; interquartile range: 1.3-2.8). Over a third had a significant disability at 2 years (Pediatric Stroke Outcome Measure >2). Total Pediatric Stroke Outcome Measure score improved over time (P=0.0003), paralleling improvements in the sensorimotor subscore (P=0.0004). Altered mental status (odds ratio, 13; 95% confidence interval, 3.9-46; P<0.001), hemorrhage volume ?4% of total brain volume (odds ratio, 17; 95% confidence interval, 1.9-156; P=0.01), and intensive care unit length of stay (odds ratio, 1.1; 95% confidence interval, 1.0-1.2; P=0.002) were significantly associated with poor 2-year outcome. CONCLUSIONS:Over one third of children experienced significant disability at 2 years. Improvements in outcomes were driven by recovery of sensorimotor function. Altered mental status, hemorrhage volume ?4% of total brain volume, and intensive care unit length of stay were independent predictors of significant disability at 2 years.
| S-EPMC6019624 | biostudies-literature
Project description:Rising intracranial pressure (ICP) aggravates secondary injury and heightens risk of death following intracerebral hemorrhage (ICH). Long-recognized compensatory mechanisms that lower ICP include reduced cerebrospinal fluid and venous blood volumes. Recently, we identified another compensatory mechanism in severe stroke, a decrease in cerebral parenchymal volume via widespread reductions in cell volume and extracellular space (tissue compliance). Here, we examined how age affects tissue compliance and ICP dynamics after severe ICH in rats (collagenase model). A planned comparison to historical young animal data revealed that aged SHAMs (no stroke) had significant cerebral atrophy (9% reduction, p ≤ 0.05), ventricular enlargement (9% increase, p ≤ 0.05), and smaller CA1 neuron volumes (21%, p ≤ 0.05). After ICH in aged animals, contralateral striatal neuron density and CA1 astrocyte density significantly increased (12% for neurons, 7% for astrocytes, p ≤ 0.05 vs. aged SHAMs). Unlike young animals, other regions in aged animals did not display significantly reduced cell soma volume despite a few trends. Nonetheless, overall contralateral hemisphere volume was 10% smaller in aged ICH animals compared to aged SHAMs (p ≤ 0.05). This age-dependent pattern of tissue compliance is not due to absent ICH-associated mass effect (83.2 mm3 avg. bleed volume) as aged ICH animals had significantly elevated mean and peak ICP (p ≤ 0.01), occurrence of ICP spiking events, as well as bilateral evidence of edema (e.g., 3% in injured brain, p ≤ 0.05 vs. aged SHAMs). Therefore, intracranial compliance reserve changes with age; after ICH, these and other age-related changes may cause greater fluctuation from baseline, increasing the chance of adverse outcomes like mortality.
| S-EPMC10640482 | biostudies-literature
Project description:As an essential constituent of the mitochondrial contact site and cristae organization system (MICOS), MIC19 plays a crucial role in maintaining the stability of mitochondrial function and microstructure. However, the mechanisms and functions of MIC19 in intracerebral hemorrhage (ICH) remain unknown and need to be investigated. Sprague Dawley (SD) rats injected with autologous blood obtained from the caudal artery, and cultured neurons exposed to oxygen hemoglobin (OxyHb) were used to establish and emulate the ICH model in vivo and in vitro. Lentiviral vector encoding MIC19 or MIC19 short hairpin ribonucleic acid (shRNA) was constructed and administered to rats by intracerebroventricular injection to overexpress or knock down MIC19, respectively. First, MIC19 protein levels were increased after ICH modeling. After virus transfection and subsequent ICH modeling, we observed that overexpression of MIC19 could mitigate cell apoptosis and neuronal death, as well as abnormalities in mitochondrial structure and function, oxidative stress within mitochondria, and neurobehavioral deficits in rats following ICH. Conversely, knockdown of MIC19 had the opposite effect. Moreover, we found that the connection between MIC19 and SAM50 was disrupted after ICH, which may be a reason for the impairment of the mitochondrial structure after ICH. In conclusion, MIC19 exerts a protective role in the subsequent injury induced by ICH. The investigation of MIC19 may offer clinicians novel therapeutic insights for patients afflicted with ICH.
| S-EPMC10380515 | biostudies-literature
Project description:AimsTo examine the relationship between statin use in Chinese patients with intracerebral hemorrhage (ICH) during their hospitalization and the outcomes.MethodsData were collected from the China National Stroke Registry. Good functional outcome was defined by a modified Rankin Scale score between 0-2. Functional outcome and rate of mortality at 3 months and 1 year were compared between ICH patients on statin and those without it during their hospitalization. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated using the multivariable logistic regression model adjusted for baseline risk factors.ResultsAmong 3218 consecutive ICH patients from 2007 to 2008, 220 (6.8%) were on statin during their hospitalization. Compared with those without statin, patients on statin were younger, had more stroke risk factors but lower stroke severity. ICH patients on statin had better functional outcome at 3 months (OR 2.24, 95% CI 1.49-3.36) and at 1 year (OR 2.04, 95% CI 1.37-3.06). They also had lower rate of mortality at 3 months (OR 0.44, 95% CI 0.22-0.87) and 1 year (OR 0.49, 95% CI 0.27-0.86).ConclusionsIn-hospital statin use in ICH patients is associated with better functional outcome and lower mortality at 3 months and 1 year.
| S-EPMC6493001 | biostudies-literature
Project description:After intracerebral hemorrhage (ICH), the brain parenchyma is exposed to blood containing red blood cells (RBCs) and consequently to its lysis products. Iron-rich hemoglobin (Hb) is the most abundant protein in RBCs. When released into the brain parenchyma during hemolysis, Hb becomes a central mediator of cytotoxicity. Our study indicates that haptoglobin (Hp), an acute-phase response protein primarily synthesized in the liver and known to bind and neutralize Hb in the bloodstream, is also expressed in brain in which it plays an important role in defending neurons from damage induced by hemolytic products after ICH. We demonstrate that the Hb-induced hypohaptoglobinemia aggravates ICH-induced brain damage while pharmacologic intervention with sulforaphane to induce brain Hp is linked to a reduction in brain damage. In agreement with these findings, Hp deficiency worsens whereas Hp overexpression alleviates ICH-mediated brain injury. We also identified that oligodendroglia are the primary source of brain-derived Hp among brain cells and that oligodendroglia-released Hp plays protective roles against Hb-mediated toxicity to neurons and oligodendrocytes. We conclude that Hp, particularly the brain-derived Hp, plays cytoprotective roles and represents a potential therapeutic target for ICH treatment.
| S-EPMC2831226 | biostudies-literature
Project description:Inflammatory responses mediated by prostaglandins such as PGE2 may contribute to secondary brain injury after intracerebral hemorrhage (ICH). However, the cell-specific signaling by PGE2 receptor EP2 differs depending on whether the neuropathic insult is acute or chronic. Using genetic and pharmacologic approaches, we investigated the role of EP2 receptor in two mouse models of ICH induced by intrastriatal injection of collagenase or autologous arterial whole blood. We used middle-aged male mice to enhance the clinical relevance of the study. EP2 receptor was expressed in neurons but not in astrocytes or microglia after collagenase-induced ICH. Brain injury after collagenase-induced ICH was associated with enhanced cellular and molecular inflammatory responses, oxidative stress, and matrix metalloproteinase (MMP)-2/9 activity. EP2 receptor deletion exacerbated brain injury, brain swelling/edema, neuronal death, and neurobehavioral deficits, whereas EP2 receptor activation by the highly selective agonist AE1-259-01 reversed these outcomes. EP2 receptor deletion also exacerbated brain edema and neurologic deficits in the blood ICH model. These findings support the premise that neuronal EP2 receptor activation by PGE2 protects brain against ICH injury in middle-aged mice through its anti-inflammatory and anti-oxidant effects and anti-MMP-2/9 activity. PGE2/EP2 signaling warrants further investigation for potential use in ICH treatment.
| S-EPMC5363749 | biostudies-literature
Project description:AimsLittle is known about the performance of the maximally treated intracerebral hemorrhage (max-ICH) score in predicting unfavorable long-term functional outcome and death in patients with intracerebral hemorrhage (ICH) in China. We aimed to validate the performance of the max-ICH score and compared it with other recognized scores.MethodsWe derived data from the China National Stroke Registry (CNSR). Receiver-operating characteristic (ROC) analysis and Hosmer-Lemeshow test were used to measure the score performance. We compared the performance of max-ICH score with six recognized models, including the ICH score, ICH functional outcome score (ICH-FOS), Essen-ICH score, modified intracerebral hemorrhage (MICH) score, intracerebral hemorrhage grading scale (ICH-GS), and functional outcome (FUNC) score.ResultsA total of 2581 patients with spontaneous ICH were enrolled in the study. The max-ICH score was similar or superior to the six existing scores in predicting long-term unfavorable functional outcome after ICH with good discrimination (AUC 0.83, 95% confidence interval [CI] 0.81-0.84) and calibration (Hosmer-Lemeshow P = 0.19). For predicting death, the AUC of max-ICH was 0.81 (95% CI 0.79-0.83).ConclusionsThe easy-to-use max-ICH score is a reliable tool to predict unfavorable long-term (12-month) functional outcome and death after intracerebral hemorrhage in the Chinese population.
| S-EPMC6489715 | biostudies-literature
Project description:ObjectiveWe tested the hypothesis that surveillance neuroimaging and neurologic examinations identified changes requiring emergent surgical interventions in patients with intracerebral hemorrhage (ICH).MethodsPatients with primary ICH were enrolled into a prospective registry between December 2006 and July 2012. Patients were managed in a neuroscience intensive care unit with a protocol that included serial neuroimaging at 6, 24, and 48 hours, and hourly neurologic examinations using the Glasgow Coma Scale and NIH Stroke Scale. We evaluated all cases of craniotomy and ventriculostomy to determine whether the procedure was part of the initial management plan or occurred subsequently. For those that occurred subsequently, we determined whether worsening on neurologic examination or worsened neuroimaging findings initiated the process leading to intervention.ResultsThere were 88 surgical interventions in 84 (35%) of the 239 patients studied, including ventriculostomy in 52 (59%), craniotomy in 21 (24%), and both in 11 (13%). Of the 88 interventions, 24 (27%) occurred subsequently and distinctly from initial management, a median of 15.9 hours (8.9-27.0 hours) after symptom onset. Thirteen (54%) were instigated by findings on neurologic examination and 11 (46%) by neuroimaging. Demographics, severity of hemorrhage, and hemorrhage location were not associated with delayed intervention.ConclusionsMore than 25% of surgical interventions performed after ICH were prompted by delayed imaging or clinical findings. Serial neurologic examinations and neuroimaging are important and effective surveillance techniques for monitoring patients with ICH.
| S-EPMC3770177 | biostudies-literature