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Complex Clearance Mechanisms After Intraventricular Hemorrhage and rt-PA Treatment —a Review on Clinical Trials
AbstractIntracerebral hemorrhage in combination with intraventricular hemorrhage (IVH) is a severe type of stroke frequently leading to prolonged clinical care, continuous disability, shunt dependency, and high mortality. The molecular mechanisms induced by IVH are complex and not fully understood. Moreover, the treatment options for IVH are limited. Intraventricular recombinant tissue plasminogen activator (rt-PA) dissolves the blood clot in the ventricular system; however, whether the clinical outcome is thereby positively affected is still being debated. The mechanistic cascade induced by intraventricular rt-PA therapy ...
Source: Translational Stroke Research - September 13, 2019 Category: Neurology Source Type: research

Low Serum Uric Acid Levels Promote Hypertensive Intracerebral Hemorrhage by Disrupting the Smooth Muscle Cell-Elastin Contractile Unit and Upregulating the Erk1/2-MMP Axis
In this study, we confirmed the association between low SUA levels and the risk for recurrence of ICH and for cardiac-cerebral vascular mortality in hypertensive patients. To determine the mechanism by which low SUA effects ICH pathogenesis, we developed the first low SUA mouse model and conducted transcriptome profiling of the cerebrovasculature of ICH mice. When combining these assessments with pathological morphology, we found that low SUA levels led to ICH in mice with angiotensin II (Ang II) –induced hypertension and aggravated the pathological progression of ICH. In vitro, our results showed that p-Erk1/2-MMP axis ...
Source: Translational Stroke Research - April 21, 2020 Category: Neurology Source Type: research

Contribution of Endoplasmic Reticulum Stress to the Clinical Instability of Carotid Plaques in Human Carotid Stenosis
AbstractEndoplasmic reticulum (ER) stress is an important process during the progression of atherosclerosis. The aim of this study was to elucidate the association of ER stress and clinical instability of carotid plaque. One hundred ninety-three patients with carotid stenosis undergoing carotid endarterectomies (CEAs) were enrolled. We classified the patients into 3 groups: the asymptomatic, symptomatic, and cTIA (crescendo transient ischemic attack)/SIE (stroke in evolution) groups. Immunohistological staining was performed to assess ER stress and apoptosis. The correlation between ER stress marker expression and clinical...
Source: Translational Stroke Research - November 16, 2021 Category: Neurology Source Type: research

Changes in Cerebral Blood Flow and Diffusion-Weighted Imaging Lesions After Intracerebral Hemorrhage
AbstractIntracerebral hemorrhage (ICH) is a common subtype of stroke and places a great burden on the family and society with a high mortality and disability rate and a poor prognosis. Many findings from imaging and pathologic studies have suggested that cerebral ischemic lesions visualized on diffusion-weighted imaging (DWI) in patients with ICH are not rare and are generally considered to be associated with poor outcome, increased risk of recurrent (ischemic and hemorrhagic) stroke, cognitive impairment, and death. In this review, we describe the changes in cerebral blood flow (CBF) and DWI lesions after ICH and discuss ...
Source: Translational Stroke Research - March 19, 2022 Category: Neurology Source Type: research

ASPECT Score and Its Application to Vasospasm in Aneurysmal Subarachnoid Haemorrhage: a Case –Control Study
AbstractDelayed cerebral ischaemia (DCI) is a significant complication of aneurysmal subarachnoid haemorrhage (aSAH) and is strongly associated with poorer outcome. The Alberta Stroke Program Early Computer Tomography (ASPECT) score is an established scoring tool, used in acute ischaemic stroke, to quantify early ischaemic changes on CT head scans. We aim to identify if ASPECT scoring correlates with functional outcome in DCI following aSAH. Retrospective case –control study. Inclusion criteria: admission to the Department of Neurosurgery at Leeds Teaching Hospitals NHS Trust (a tertiary neurosurgical centre in the Unite...
Source: Translational Stroke Research - August 9, 2022 Category: Neurology Source Type: research

Intracranial Pressure Dysfunction Following Severe Intracerebral Hemorrhage in Middle-Aged Rats
AbstractRising 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 rev...
Source: Translational Stroke Research - November 11, 2022 Category: Neurology Source Type: research

The Rabbit Shunt Model of Subarachnoid Haemorrhage
Abstract Aneurysmal subarachnoid haemorrhage (SAH) is a disease with devastating complications that leads to stroke, permanent neurological deficits and death. Clinical and ex-perimental work has demonstrated the importance of the contribution of delayed cerebral vasospasm (DCVS) indepen-dent early events to mortality, morbidity and functional out-come after SAH. In order to elucidate processes involved in early brain injury (EBI), animal models that reflect acute events of aneurysmal bleeding, such as increase in intracranial pressure (ICP) and decrease in cerebral perfusion pressure, are needed. In the presented...
Source: Translational Stroke Research - October 19, 2014 Category: Neurology Source Type: research

Brainstem Opioidergic System Is Involved in Early Response to Experimental SAH
In this study, we have demonstrated that ablation of μ-opioid receptor containing cells with dermorphin conjugates in the RVM results in a high mortality rate after experimental SAH and, in survivors, causes a dramatic decrease in CBF. Further, locally blocking the μ-opioid receptor with the antagonist naltrexone attenuated the reduction in CBF secondary to experimental SAH. Saturating μ-opioid receptors with the agonist [d-Ala(2),NMe-Phe(4),Gly-ol(5)]-encephalin (DAMGO) had no effect. Taken together, these results suggest that SAH activates opioidergic signaling in the RVM with a resultant reduction in CBF. Further, ce...
Source: Translational Stroke Research - November 25, 2014 Category: Neurology Source Type: research

The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid (SAHA) Confers Acute Neuroprotection After Intracerebral Hemorrhage in Mice
Abstract Spontaneous intracerebral hemorrhage (ICH) is a stroke subtype with no effective treatment. Though ICH is known to induce severe neurological damage, the molecular mechanisms of neurological injury after ICH remain largely unclear. Given the emerging role of epigenetic mechanisms in neurodegeneration, the present study evaluated whether suberoylanilide hydroxamic acid (SAHA: vorinostat), a clinically well-tolerated pan-histone deacetylase inhibitor (HDACi), would attenuate neurological injury and improve functional outcomes in a preclinical model of ICH. Mice were administered with SAHA or vehicle after a...
Source: Translational Stroke Research - September 4, 2015 Category: Neurology Source Type: research

Matched Cohort Analysis of the Effects of Limb Remote Ischemic Conditioning in Patients with Aneurysmal Subarachnoid Hemorrhage
In this study, we aim to detect the potential effect of an established lower-limb conditioning protocol on clinical outcomes of aSAH patients. Neurologic outcome (modified Rankin Scale (mRS)) of patients enrolled in a prospective trial (RIPC-SAH) was measured. A matching algorithm was applied to identify control patients with aSAH from an institutional departmental database. RIC patients underwent four lower-limb conditioning sessions, consisting of four 5-min cycles per session over nonconsecutive days. Good functional outcome was defined as mRS of 0 to 2. The study population consisted of 21 RIC patients and 61 matched c...
Source: Translational Stroke Research - December 2, 2015 Category: Neurology Source Type: research

Author Correction: Predictors for Intracranial Hemorrhage Following Intravenous Thrombolysis in Posterior Circulation Stroke
AbstractIn the original publication of the article, there was a switched order of author names.
Source: Translational Stroke Research - March 5, 2018 Category: Neurology Source Type: research

Neutrophil-to-Lymphocyte Ratio in Acute Cerebral Hemorrhage: a System Review
AbstractSpontaneous intracerebral hemorrhage (ICH) accounts for approximately 10 to 30% of all acute cerebrovascular events, and it is the type of stroke associated with the highest rates of mortality and residual disability. The inflammatory response is early triggered by hematoma components and can enhance the damage within the hemorrhagic brain. Assessment of peripheral biomarkers of inflammation could contribute to increase knowledge about some of the mechanisms involved in the ICH-induced injury and yield information on the disease course. The neutrophil-to-lymphocyte ratio (NLR) integrates information on both the inn...
Source: Translational Stroke Research - August 8, 2018 Category: Neurology Source Type: research

Apolipoprotein E Exerts a Whole-Brain Protective Property by Promoting M1? Microglia Quiescence After Experimental Subarachnoid Hemorrhage in Mice
We reported thatApoe deficiency resulted in a more extensive EBI at 48  h after SAH in mice demonstrated by MRI scanning and immunohistochemical staining and exhibited more extensive white matter injury and neuronal apoptosis than WT mice. These changes were associated with an increase in NADPH oxidase 2 (NOX2) expression, an important regulator of both oxidative stre ss and inflammatory cytokines. Furthermore, immunohistochemical analysis revealed that NOX2 was abundantly expressed in activated M1 microglia. The JAK2/STAT3 signaling pathway, an upstream regulator of NOX2, was increased in WT mice and activated to an even...
Source: Translational Stroke Research - September 17, 2018 Category: Neurology Source Type: research

Recombinant Adiponectin Peptide Ameliorates Brain Injury Following Intracerebral Hemorrhage by Suppressing Astrocyte-Derived Inflammation via the Inhibition of Drp1-Mediated Mitochondrial Fission
In conclusion, we propose APNp as a potential therapeutic agent for ICH. We provide the first mechanistic evidence that APNp can modulate Drp1-mediated mitochondrial fission, which then contributes to alleviating astrocyte-derived inflammation.
Source: Translational Stroke Research - January 3, 2020 Category: Neurology Source Type: research

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