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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

Prior Antiplatelet Therapy, Excluding Phosphodiesterase Inhibitor Is Associated with Poor Outcome in Patients with Spontaneous Intracerebral Haemorrhage
In this study, ADP-I and COX-1, but not PDE-I, are the most likely contributors to the association of APT with poor outcome with spontaneous ICH patients. These findings suggest that the complexity of the different mechanism of actions of prior APT can alter the outcome in spontaneous ICH.
Source: Translational Stroke Research - August 23, 2019 Category: Neurology Source Type: research

Hydrogel-Based Therapy for Brain Repair After Intracerebral Hemorrhage
This study provides proof-of-principle that injectable biomaterials may be a translationally relevant approach for treating ICH.
Source: Translational Stroke Research - August 19, 2019 Category: Neurology Source Type: research

Correction to: Intracerebral Hemorrhage –Induced Brain Injury in Rats: the Role of Extracellular Peroxiredoxin 2
In Figure 1, molecular weight of peroxiredoxin 2 (PRX-2) is 22 kDa rather than 32 kDa.
Source: Translational Stroke Research - August 8, 2019 Category: Neurology Source Type: research

AAV/BBB-Mediated Gene Transfer of CHIP Attenuates Brain Injury Following Experimental Intracerebral Hemorrhage
AbstractCell death is a hallmark of secondary brain injury following intracerebral hemorrhage (ICH). The E3 ligase CHIP has been reported to play a key role in mediating necroptosis —an important mechanism of cell death after ICH. However, there is currently no evidence supporting a function of CHIP in ICH. In the present study, we aimed to determine whether CHIP plays an essential role in brain injury after ICH. Our findings indicated that CHIP expression was increased in th e peri-hematomal area in rat models of ICH. The AAV/BBB viral platform enables non-invasive, widespread, and long-lasting global neural expression ...
Source: Translational Stroke Research - July 18, 2019 Category: Neurology Source Type: research

Intracerebral Hemorrhage –Induced Brain Injury in Rats: the Role of Extracellular Peroxiredoxin 2
AbstractRed blood cell (RBC) lysis within the hematoma causes brain injury following intracerebral hemorrhage. Peroxiredoxin 2 (PRX-2) is the third most abundant protein in RBCs and this study examined the potential role of PRX-2 in inducing brain injury in rats. First, adult male Sprague-Dawley rats had an intracaudate injection of lysed RBCs or saline. Brains were harvested at 1  h to measure PRX-2 levels. Second, rats had an intracaudate injection of either recombinant PRX-2, heat-inactivated PRX-2, or saline. Third, rats had intracaudate co-injection of lysed RBCs with conoidin A, a PRX-2 inhibitor, or vehicle. For th...
Source: Translational Stroke Research - July 3, 2019 Category: Neurology Source Type: research

Inflammation: a Good Research Target to Improve Outcomes of Poor-Grade Subarachnoid Hemorrhage
Source: Translational Stroke Research - June 17, 2019 Category: Neurology Source Type: research

Exploration of MST1-Mediated Secondary Brain Injury Induced by Intracerebral Hemorrhage in Rats via Hippo Signaling Pathway
AbstractIntracerebral hemorrhage (ICH) is a serious public health problem which causes high rates of disability and mortality in adults. Cell apoptosis is a sign of secondary brain injury (SBI) following ICH. Mammalian sterile 20-like kinase-1 (MST1), an apoptosis-promoting kinase, is a part of the Hippo signaling pathway and involved in cell death, oxidative stress, and inflammation. However, the role and underlying mechanism of MST1 in SBI induced by ICH have not yet been fully explained. The main purpose of present research was to explore the role of MST1 and its potential mechanism in SBI after ICH. An ICH model was es...
Source: Translational Stroke Research - April 1, 2019 Category: Neurology Source Type: research

Healthcare Economics of Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage in the United States
AbstractHydrocephalus is one of the most common sequelae after aneurysmal subarachnoid hemorrhage (aSAH), and it is a large contributor to the condition ’s high rates of readmission and mortality. Our objective was to quantify the healthcare resource utilization (HCRU) and health economic burden incurred by the US health system due to post-aSAH hydrocephalus. The Truven Health MarketScan® Research database was used to retrospectively quantify the prevalence and HCRU associated with hydrocephalus in aSAH patients undergoing surgical clipping or endovascular coiling from 2008 to 2015. Multivariable longitudinal analysis w...
Source: Translational Stroke Research - March 12, 2019 Category: Neurology Source Type: research

Two Diverse Hemodynamic Forces, a Mechanical Stretch and a High Wall Shear Stress, Determine Intracranial Aneurysm Formation
AbstractIntracranial aneurysm (IA) usually induced at a bifurcation site of intracranial arteries causes a lethal subarachnoid hemorrhage. Currently, IA is considered as a macrophage-mediated inflammatory disease triggered by a high wall shear stress (WSS) on endothelial cells. However, considered the fact that a high WSS can be observed at every bifurcation site, some other factors are required to develop IAs. We therefore aimed to clarify mechanisms underlying the initiation of IAs using a rat model. We found the transient outward bulging and excessive mechanical stretch at a prospective site of IA formation. Fibroblasts...
Source: Translational Stroke Research - February 8, 2019 Category: Neurology Source Type: research

Lactate Dehydrogenase Predicts Early Hematoma Expansion and Poor Outcomes in Intracerebral Hemorrhage Patients
In conclusion, LD H is a reliable predictor for early hematoma expansion and poor outcomes in patients with ICH.
Source: Translational Stroke Research - January 31, 2019 Category: Neurology Source Type: research

Loss of Endothelial Laminin α5 Exacerbates Hemorrhagic Brain Injury
In this study, we generated endothelium-specific lama5 conditional knockout ( α5-TKO) mice and investigated the biological functions of endothelial lama5 in blood-brain barrier (BBB) maintenance under homeostatic conditions and the pathogenesis of intracerebral hemorrhage (ICH). First, the BBB integrity of α5-TKO mice was measured under homeostatic conditions. Next, ICH was induced in α5-TKO mice and their littermate controls using the collagenase model. Various parameters, including injury volume, neuronal death, neurological score, brain edema, BBB integrity, inflammatory cell infiltration, and gliosis, were examined ...
Source: Translational Stroke Research - January 29, 2019 Category: Neurology Source Type: research

The Role of Oxidative Stress in Microvascular Disturbances after Experimental Subarachnoid Hemorrhage
AbstractOxidative stress was shown to play a crucial role in the diverse pathogenesis of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Microcirculatory dysfunction is thought to be an important and fundamental pathological change in EBI. However, other than blood-brain barrier (BBB) disruption, the influence of oxidative stress on microvessels remains to be elucidated. The aim of this study was to investigate the role of oxidative stress on microcirculatory integrity in EBI. SAH was induced in male Sprague-Dawley rats using an endovascular perforation technique. A free radical scavenger, edaravone, was admi...
Source: Translational Stroke Research - January 9, 2019 Category: Neurology Source Type: research

Management of Cerebral Microbleeds in Clinical Practice
AbstractCerebral microbleeds (CMBs) are very frequent diagnoses with MRI imaging in the elderly or in patients with cerebral infarction, intracranial hemorrhage (ICH), and dementia. The mechanisms for CMBs are not fully understood but may be secondary to injury to the vascular wall from long-standing hypertension or amyloid deposition in the tissue. The presence of CMB increases the risk for stroke, dementia, and death. The increasing number of CMBs is also associated with a higher risk of hemorrhagic complications with the long-term use of anticoagulants in atrial fibrillation and in patients requiring thrombolysis for ac...
Source: Translational Stroke Research - December 15, 2018 Category: Neurology Source Type: research

Induction of Brain Arteriovenous Malformation Through CRISPR/Cas9-Mediated Somatic Alk1 Gene Mutations in Adult Mice
AbstractBrain arteriovenous malformation (bAVM) is an important risk factor for intracranial hemorrhage. The pathogenesis of bAVM has not been fully understood. Animal models are important tools for dissecting bAVM pathogenesis and testing new therapies. We have developed several mouse bAVM models using genetically modified mice. However, due to the body size, mouse bAVM models have some limitations. Recent studies identified somatic mutations in sporadic human bAVM. To develop a feasible tool to create sporadic bAVM in rodent and animals larger than rodent, we made tests using the CRISPR/Cas9 technique to induce somatic g...
Source: Translational Stroke Research - December 3, 2018 Category: Neurology Source Type: research

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