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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

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

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

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

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

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

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

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