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Translational Molecular Imaging Tool of Vulnerable Carotid Plaque: Evaluate Effects of Statin Therapy on Plaque Inflammation and American Heart Association –Defined Risk Levels in Cuff-Implanted Apolipoprotein E–Deficient Mice
AbstractIdentification of high-risk carotid plaques in asymptomatic patients remains a challenging but crucial step in stroke prevention. The challenge is to accurately monitor the development of high-risk carotid plaques and promptly identify patients, who are unresponsive to best medical therapy, and hence targeted for carotid surgical interventions to prevent stroke. Inflammation is a key operator in destabilisation of plaques prior to clinical sequelae. Currently, there is a lack of imaging tool in routine clinical practice, which allows assessment of inflammatory activity within the atherosclerotic plaque. Herein, we ...
Source: Translational Stroke Research - December 9, 2022 Category: Neurology Source Type: research

Deferoxamine Prevents Neonatal Posthemorrhagic Hydrocephalus Through Choroid Plexus-Mediated Iron Clearance
AbstractPosthemorrhagic hydrocephalus occurs in up to 30% of infants with high-grade intraventricular hemorrhage and is associated with the worst neurocognitive outcomes in preterm infants. The mechanisms of posthemorrhagic hydrocephalus after intraventricular hemorrhage are unknown; however, CSF levels of iron metabolic pathway proteins including hemoglobin have been implicated in its pathogenesis. Here, we develop an animal model of intraventricular hemorrhage using intraventricular injection of hemoglobin at post-natal day 4 that results in acute and chronic  hydrocephalus, pathologic choroid plexus iron accumulation, ...
Source: Translational Stroke Research - October 29, 2022 Category: Neurology Source Type: research

Development of Molecular Magnetic Resonance Imaging Tools for Longitudinal Tracking of Carotid Atherosclerotic Disease Using Fast Imaging with Steady-State Precession
AbstractIdentification of patients with high-risk asymptomatic carotid plaques remains a challenging but essential step in stroke prevention. Current selection criteria for intervention in carotid disease are still determined by symptomatology and degree of luminal stenosis. This strategy has been less effective in identifying the high-risk asymptomatic individual patients. Inflammation is the key factor that drives plaque instability causing clinical sequelae. Currently, there is no imaging tool in routine clinical practice to assess the inflammatory status within atherosclerotic plaques. Herein we describe the developmen...
Source: Translational Stroke Research - July 18, 2022 Category: Neurology Source Type: research

Iron-Induced Hydrocephalus: the Role of Choroid Plexus Stromal Macrophages
In conclusion, stromal macrophages account for ~10% of all choroid plexus cells, with more in aged rats. Treatments targeting macrophages (minocycline and clodronate liposomes) are associated with reduced iron-induced hydrocephalus.
Source: Translational Stroke Research - May 11, 2022 Category: Neurology Source Type: research

Extended Ischemic Recovery After Implantation of Human Mesenchymal Stem Cell Aggregates Indicated by Sodium MRI at 21.1  T
AbstractExtended therapeutic application remains a significant issue in the use of stem cell therapies to treat ischemic stroke. Along these lines, neurological recovery in a rodent model of ischemic stroke was evaluated following implantation of human mesenchymal stem cell aggregates (hMSC-agg), labeled with micron-sized particles of iron oxide, directly into the lateral ventricle contralateral to the ischemic lesion hemisphere. Longitudinally, disease progression and response to hMSC-agg therapy were assessed by1H and23Na magnetic resonance imaging (MRI) at 21.1  T to investigate cellular localization, migration, and re...
Source: Translational Stroke Research - February 7, 2022 Category: Neurology Source Type: research

The Fate of Erythrocytes after Cerebral Hemorrhage
AbstractAfter a cerebral hemorrhage (intracerebral, subarachnoid, and intraventricular), extravasated blood contributes to both initial brain injury, via physical disruption and mass effect, and secondary injury, through the release of potentially neurotoxic and pro-inflammatory factors such as hemoglobin, iron, and peroxiredoxin-2. Erythrocytes are a major blood component and are a source of such damaging factors. Erythrolysis after cerebral hemorrhage releases potential neurotoxins, contributing to brain injury and edema. Alternatively, erythrocyte phagocytosis via microglia or macrophages may limit the spill of neurotox...
Source: Translational Stroke Research - January 23, 2022 Category: Neurology Source Type: research

Development of Molecular Magnetic Resonance Imaging Tools for Risk Stratification of Carotid Atherosclerotic Disease Using Dual-Targeted Microparticles of Iron Oxide
AbstractIdentification of patients with high-risk asymptomatic carotid plaques remains a challenging but crucial step in stroke prevention. Inflammation is the key factor that drives plaque instability. Currently, there is no imaging tool in routine clinical practice to assess the inflammatory status within atherosclerotic plaques. We have developed a molecular magnetic resonance imaging (MRI) tool to quantitatively report the inflammatory activity in atherosclerosis using dual-targeted microparticles of iron oxide (DT-MPIO) against P-selectin and VCAM-1 as a smart MRI probe. A periarterial cuff was used to generate plaque...
Source: Translational Stroke Research - July 25, 2021 Category: Neurology Source Type: research

Deferoxamine Treatment Prevents Post-Stroke Vasoregression and Neurovascular Unit Remodeling Leading to Improved Functional Outcomes in Type 2 Male Diabetic Rats: Role of Endothelial Ferroptosis
This study aimed to determine the impact of iron chelation with deferoxamine (DFX) on (1) cerebral vascularization patterns and (2) functional outcomes after stroke in control and diabetic rats. After 8  weeks of type 2 diabetes induced by a combination of high-fat diet and low-dose streptozotocin, male control and diabetic animals were subjected to thromboembolic middle cerebral artery occlusion (MCAO) and randomized to vehicle, DFX, or tPA/DFX and followed for 14 days with behavioral tests. Vas cular indices (vascular volume and surface area), neurovascular remodeling (AQP4 polarity), and microglia activation were meas...
Source: Translational Stroke Research - August 31, 2020 Category: Neurology Source Type: research

Clot Analog Attenuation in Non-contrast CT Predicts Histology: an Experimental Study Using Machine Learning
AbstractExact histological clot composition remains unknown. The purpose of this study was to identify the best imaging variables to be extrapolated on clot composition and clarify variability in the imaging of thrombi by non-contrast CT. Using a CT-phantom and covering a wide range of histologies, we analyzed 80 clot analogs with respect to X-ray attenuation at 24 and 48  h after production. The mean, maximum, and minimum HU values for the axial and coronal reconstructions were recorded. Each thrombus underwent a corresponding histological analysis, together with a laboratory analysis of water and iron contents. Decision...
Source: Translational Stroke Research - January 13, 2020 Category: Neurology Source Type: research

Quantitative Iron Neuroimaging Can Be Used to Assess the Effects of Minocycline in an Intracerebral Hemorrhage Minipig Model
This study was performed to investigate the noninvasive neuroimaging method for quantifying brain iron content using a minipig ICH model and assess the effects of minocycline treatment on ICH-induced iron overload and brain injury. The minipig ICH model was established by injecting 2  ml of autologous blood into the right basal ganglia, which were then subjected to the treatments of minocycline and vehicle. Furthermore, the quantitative susceptibility mapping (QSM) was used to quantify iron content, and diffusion tensor imaging (DTI) was performed to evaluate white matter tract . Additionally, we also performed immunohist...
Source: Translational Stroke Research - November 5, 2019 Category: Neurology Source Type: research

CD47 Blocking Antibody Accelerates Hematoma Clearance After Intracerebral Hemorrhage in Aged Rats
This study expands those findings by examining the effects on a CD47 blocking antibody in aged rats. First, male Fischer 344 rats (18 months old) received an intracaudate injection of 50 μL auto logous whole blood or saline. Hematoma features of magnetic resonance imaging (MRI) and neurological deficits were evaluated within 3 days. Second, rats had an intracaudate co-injection of 50 μL autologous blood with either CD47 blocking antibody or IgG. MRI was used to quantify hematoma/iron vol ume, hemolysis, brain swelling, and atrophy at different time points, behavioral tests to assess neurological deficits, and immunoh...
Source: Translational Stroke Research - October 29, 2019 Category: Neurology Source Type: research

A Brain-Targeted Orally Available ROCK2 Inhibitor Benefits Mild and Aggressive Cavernous Angioma Disease
AbstractCavernous angioma (CA) is a vascular pathology caused by loss of function in one of the 3 CA genes (CCM1,CCM2, andCCM3) that result in rho kinase (ROCK) activation. We investigated a novel ROCK2 selective inhibitor for the ability to reduce brain lesion formation, growth, and maturation. We used genetic methods to explore the use of a ROCK2-selective kinase inhibitor to reduce growth and hemorrhage of CAs. The role of ROCK2 in CA was investigated by crossingRock1 orRock2 hemizygous mice withCcm1 orCcm3 hemizygous mice, and we found reduced lesions in theRock2 hemizygous mice. A ROCK2-selective inhibitor, BA-1049 wa...
Source: Translational Stroke Research - August 23, 2019 Category: Neurology Source Type: research

Brain Ceruloplasmin Expression After Experimental Intracerebral Hemorrhage and Protection Against Iron-Induced Brain Injury
This study had two parts: first, rats had injection of autologous blood into the right basal ganglia and the time course of CP expression in the brain examined (protein and mRNA). Second, rats had an injection of either Fe2+ in saline, Fe2+ plus CP in saline, or saline alone into the right basal ganglia. All rats in the second part had T2-weighted magnetic resonance imaging, and behavioral tests before the brains were harvested for immunohistochemistry and Western blotting. We found that CP was expressed on neurons and astrocytes in both cortex and basal ganglia after ICH. The time course showed that ICH induced CP express...
Source: Translational Stroke Research - October 12, 2018 Category: Neurology Source Type: research