Refined Ischemic Penumbra Imaging with Tissue pH and Diffusion Kurtosis Magnetic Resonance Imaging
AbstractImaging has played a vital role in our mechanistic understanding of acute ischemia and the management of acute stroke patients. The most recent DAWN and DEFUSE-3 trials showed that endovascular therapy could be extended to a selected group of late-presenting stroke patients with the aid of imaging. Although perfusion and diffusion MRI have been commonly used in stroke imaging, the approximation of their mismatch as the penumbra is oversimplified, particularly in the era of endovascular therapy. Briefly, the hypoperfusion lesion includes the benign oligemia that does not proceed to infarction. Also, with prompt and ...
Source: Translational Stroke Research - September 6, 2021 Category: Neurology Source Type: research

Irreversible Neuronal Damage Begins Just After Aneurysm Rupture in Poor-Grade Subarachnoid Hemorrhage Patients
AbstractPathophysiological findings of early brain injury in humans have not permitted conclusive determinations. We explored the essence of this phenomenon by taking intraoperative cortical specimens of Hunt-Kosnik grades IV~V (poor-grade) subarachnoid hemorrhages (SAH). From 2013 to 2017, we treated 39 consecutive poor-grade patients in 226 cases of aneurysmal SAH. Fourteen of the 39 patients agreed to this study following written informed consent. We took specimens from untouched areas prior to surgical intervention: cortex near the ruptured aneurysm for clipping, convexity cortex for cerebral ventricular drainage. Cort...
Source: Translational Stroke Research - September 6, 2021 Category: Neurology Source Type: research

Protective Effects of ShcA Protein Silencing for Photothrombotic Cerebral Infarction
This study suggests that the regulation of ShcA protein expression can be a therapeutic target for reducing brain damage with mitochondrial dysfunction caused by thrombotic infarction. (Source: Translational Stroke Research)
Source: Translational Stroke Research - September 6, 2021 Category: Neurology Source Type: research

Novel Metabolites as Potential Indicators of Ischemic Infarction Volume: a Pilot Study
AbstractMetabolomics may identify biomarkers for acute ischemic stroke (AIS). Previously, circulating metabolites were compared in AIS and healthy controls without accounting for stroke size. The goal of this study was to identify metabolites that associate with the volume of AIS. We prospectively analyzed 1554 serum metabolites in the acute (72  h) and chronic (3–6 months) stages of 60 ischemic stroke patients. We calculated infarct volume using diffusion-weighted images with MR segmentation software and associated the volume with stage-specific metabolites, acute-to-chronic stage changes, and multiple mix...
Source: Translational Stroke Research - September 6, 2021 Category: Neurology Source Type: research

Molecular Correlates of Hemorrhage and Edema Volumes Following Human Intracerebral Hemorrhage Implicate Inflammation, Autophagy, mRNA Splicing, and T Cell Receptor Signaling
AbstractIntracerebral hemorrhage (ICH) and perihematomal edema (PHE) volumes are major determinants of ICH outcomes as is the immune system which plays a significant role in damage and repair. Thus, we performed whole-transcriptome analyses of 18 ICH patients to delineate peripheral blood genes and networks associated with ICH volume, absolute perihematomal edema (aPHE) volume, and relative PHE (aPHE/ICH; rPHE). We found 440, 266, and 391 genes correlated with ICH and aPHE volumes and rPHE, respectively (p   |0.6|). These mainly represented inflammatory pathways including NF-κB, TREM1, and Neuroinflamma...
Source: Translational Stroke Research - September 6, 2021 Category: Neurology Source Type: research

Predicting Atrial Fibrillation with High Risk of Embolization with Atrial Strain and NT-proBNP
AbstractThe aim of the study was to determine markers of atrial dysfunction in patients with cryptogenic stroke to predict episodes of paroxysmal atrial fibrillation with high risk of embolization (HpAF). We classified patients included in the Crypto-AF study, Cryptogenic Stroke registry, to detect paroxysmal atrial fibrillation (pAF) with wearable Holter, according to the longest episode of pAF in three groups: without pAF detection, episodes of pAF shorter than 5  h, and episodes of pAF longer than 5 h (HpAF). Atrial dysfunction surrogates were evaluated: EKG pattern, Holter record and echocardiography paramete...
Source: Translational Stroke Research - September 6, 2021 Category: Neurology Source Type: research

Nicotine Exposure Along with Oral Contraceptive Treatment in Female Rats Exacerbates Post-cerebral Ischemic Hypoperfusion Potentially via Altered Histamine Metabolism
AbstractSmoking-derived nicotine (N) and oral contraceptives (OCs) synergistically exacerbate ischemic brain damage in the female, and the underlying mechanisms remain elusive. Our published study showed that N toxicity is exacerbated by OC via altered mitochondrial electron transport chain function. Because mitochondria play an important role in cellular metabolism, we investigated the global metabolomic profile of brains of adolescent and adult female Sprague-Dawley rats exposed to N with or without OC (N+/ −OC). Rats were randomly exposed to saline or N+/−OC for 16–21 days followed by random alloc...
Source: Translational Stroke Research - September 6, 2021 Category: Neurology Source Type: research

Increased Stroke Risk in Metabolically Abnormal Normal Weight: a 10-Year Follow-up of 102,037 Participants in China
AbstractThe purpose of this study was to investigate the risks of stroke in subjects with metabolically abnormal normal weight (MANW) in China. We recruited 102,037 participants from the Zhejiang Metabolic Syndrome Cohort and the Kailuan cohort. The mean years of follow-up were 9.9  years. General obesity was defined by body mass index (BMI) ≥ 28, overweight by BMI 
Source: Translational Stroke Research - September 6, 2021 Category: Neurology Source Type: research

Intra-hematomal White Matter Tracts Act As a Scaffold for Macrophage Infiltration After Intracerebral Hemorrhage
In conclusion, white matter fibers exist within the hematoma after ICH and macrophages/microglia may use such fibers as a scaffold to infiltrate into the hematoma and aid in hematoma clearance. (Source: Translational Stroke Research)
Source: Translational Stroke Research - September 6, 2021 Category: Neurology Source Type: research

Platelet Activation and Chemokine Release Are Related to Local Neutrophil-Dominant Inflammation During Hyperacute Human Stroke
This study provides human evidence of cerebral platelet activation and platelet-neutrophil interactions during AIS and points to the relevance of per-ischemic thrombo-inflammatory mechanisms to impaired reperfusion and worse functional outcome following recanalization. (Source: Translational Stroke Research)
Source: Translational Stroke Research - August 28, 2021 Category: Neurology Source Type: research

A Novel Mutation in COL4A1 Gene in a Chinese Family with Pontine Autosomal Dominant Microangiopathy and Leukoencephalopathy
We report a novel collagen type IV alpha 1 (COL4A1) gene mutation in a Chinese family with PADMAL. The index case was followed up for 6  years. Neuroimaging, whole-exome sequencing, skin biopsy, and pedigree analysis were performed. She initially presented with minor head injury at age 38. MRI brain showed chronic lacunar infarcts in the pons, left thalamus, and right centrum semiovale. Extensive workup was unremarkable except for a patent foramen ovale (PFO). Despite anticoagulation, PFO closure, and antiplatelet therapy, the patient had recurrent lacunar infarcts in the pons and deep white matter, as well as subcort...
Source: Translational Stroke Research - August 20, 2021 Category: Neurology Source Type: research

Extended Middle Cerebral Artery Occlusion (MCAO) Model to Mirror Stroke Patients Undergoing Thrombectomy
AbstractStroke remains a leading global cause of death and disability. In the last decade, the therapeutic window for mechanical thrombectomy has increased from a maximum of 6 to 24  h and beyond. While endovascular advancements have improved rates of recanalization, no post-stroke pharmacotherapeutics have been effective in enhancing neurorepair and recovery. New experimental models are needed to closer mimic the human patient. Our group has developed a model of transient 5-h occlusion in rats to mimic stroke patients undergoing thrombectomy. Our procedure was designed specifically in aged rats and was optimized base...
Source: Translational Stroke Research - August 16, 2021 Category: Neurology Source Type: research

Development of Machine Learning Models to Predict Probabilities and Types of Stroke at Prehospital Stage: the Japan Urgent Stroke Triage Score Using Machine Learning (JUST-ML)
AbstractIn conjunction with recent advancements in machine learning (ML), such technologies have been applied in various fields owing to their high predictive performance. We tried to develop prehospital stroke scale with ML. We conducted multi-center retrospective and prospective cohort study. The training cohort had eight centers in Japan from June 2015 to March 2018, and the test cohort had 13 centers from April 2019 to March 2020. We use the three different ML algorithms (logistic regression, random forests, XGBoost) to develop models. Main outcomes were large vessel occlusion (LVO), intracranial hemorrhage (ICH), suba...
Source: Translational Stroke Research - August 14, 2021 Category: Neurology Source Type: research

Machine Learning-Enabled Determination of Diffuseness of Brain Arteriovenous Malformations from Magnetic Resonance Angiography
AbstractThe diffuseness of brain arteriovenous malformations (bAVMs) is a significant factor in surgical outcome evaluation and hemorrhagic risk prediction. However, there are still predicaments in identifying diffuseness, such as the judging variety resulting from different experience and difficulties in quantification. The purpose of this study was to develop a machine learning (ML) model to automatically identify the diffuseness of bAVM niduses using three-dimensional (3D) time-of-flight magnetic resonance angiography (TOF-MRA) images. A total of 635 patients with bAVMs who underwent TOF-MRA imaging were enrolled. Three...
Source: Translational Stroke Research - August 12, 2021 Category: Neurology Source Type: research

Inhibition of AMPA ( α-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionate) Receptor Reduces Acute Blood–Brain Barrier Disruption After Subarachnoid Hemorrhage in Mice
This study was conducted to evaluate if AMPAR activation induces acute blood–brain barrier (BBB) disruption after SAH . C57BL/6 male adult mice (n = 117) underwent sham or filament perforation SAH modeling, followed by a random intraperitoneal injection of vehicle or two dosages (1 mg/kg or 3 mg/kg) of a selective noncompetitive AMPAR antagonist perampanel (PER) at 30 min post-modeling. The effects were evaluated by mortality, neurolog ical scores, and brain water content at 24–48 h and video electroencephalogram monitoring, immunostaining, and Western blotting at 24 h pos...
Source: Translational Stroke Research - August 3, 2021 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

Ligands of the Neuropeptide Y Y2 Receptors as a Potential Multitarget Therapeutic Approach for the Protection of the Neurovascular Unit Against Acute Ischemia/Reperfusion: View from the Perspective of the Laboratory Bench
AbstractIschemic stroke is the third leading cause of death and disability worldwide, with no available satisfactory prevention or treatment approach. The current treatment is limited to the use of “reperfusion methods,” i.e., an intravenous or intra-arterial infusion of a fibrinolytic agent, mechanical removal of the clot by thrombectomy, or a combination of both methods. It should be stressed, however, that only approximately 5% of all acute strokes are eligible for fibrinolytic treatmen t and fewer than 10% for thrombectomy. Despite the tremendous progress in understanding of the pathomechanisms of cerebral ...
Source: Translational Stroke Research - July 22, 2021 Category: Neurology Source Type: research

Plasma Kallikrein Contributes to Intracerebral Hemorrhage and Hypertension in Stroke-Prone Spontaneously Hypertensive Rats
This report investigates the role of PKa on hemorrhage and hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP were fed with a high salt –containing stroke-prone diet to increase blood pressure and induce intracerebral hemorrhage. The roles of PKa on blood pressure, hemorrhage, and survival in SHRSP were examined in rats receiving a PKa inhibitor or plasma prekallikrein antisense oligonucleotide (PK ASO) compared with rats receivin g control ASO. Effects on PKa on the proteolytic cleavage of atrial natriuretic peptide (ANP) were analyzed by tandem mass spectrometry. We show that SHRSP on high-...
Source: Translational Stroke Research - July 9, 2021 Category: Neurology Source Type: research

Blocking Hepatoma-Derived Growth Factor Attenuates Vasospasm and Neuron Cell Apoptosis in Rats Subjected to Subarachnoid Hemorrhage
This study explored the relationship between SAH and HDGF. Sixty rats were divided into five groups (n  = 12/group): (A) control group; (B) rHDGF ab only group [normal animals treated with 50 µM recombinant HDGF antibodies (rHDGF ab)]; (C) SAH group; (D) SAH + pre-rHDGF ab group (SAH animals pre-treated with 50 µM rHDGF ab into the subarachnoid space within 24 h before SAH); and (E) SAH  + post-rHDGF ab group (SAH animals post-treated with 50 µM rHDGF ab into the subarachnoid space within 24 h after SAH). At 48 h after SAH, serum and ...
Source: Translational Stroke Research - July 5, 2021 Category: Neurology Source Type: research

Four Decades of Ischemic Penumbra and Its Implication for Ischemic Stroke
AbstractThe ischemic penumbra defined four decades ago has been the main battleground of ischemic stroke. The evolving ischemic penumbra concept has been providing insight for the development of vascular and cellular approaches as well as diagnostic tools for the treatment of ischemic stroke. rt-PA thrombolytic therapy to prevent the transition of ischemic penumbra to core has been approved for acute ischemic stroke within 3  h and was later recommended to extend to 4.5 h after symptom onset. Mechanical thrombectomy was introduced for the treatment of acute ischemic stroke with a therapeutic window of up to 24&nb...
Source: Translational Stroke Research - July 5, 2021 Category: Neurology Source Type: research

Correction to: Inhibition of Dectin-1 Ameliorates Neuroinflammation by Regulating Microglia/Macrophage Phenotype After Intracerebral Hemorrhage in Mice
A Correction to this paper has been published:https://doi.org/10.1007/s12975-021-00919-z (Source: Translational Stroke Research)
Source: Translational Stroke Research - July 3, 2021 Category: Neurology Source Type: research

PRIMED2 Preclinical Evidence Scoring Tool to Assess Readiness for Translation of Neuroprotection Therapies
AbstractMany neuroprotective and other therapies for treatment of acute ischemic stroke have failed in translation to human studies, indicating a need for more rigorous, multidimensional quality assessment of the totality of preclinical evidence supporting a therapy prior to conducting human trials. A consensus panel of stroke preclinical model and human clinical trial experts assessed candidate items for the translational readiness scale, compiled from prior instruments (STAIR, ARRIVE, CAMARADES, RoB 2) based on importance, reliability, and feasibility. Once constructed, the tool was applied by two independent raters to f...
Source: Translational Stroke Research - July 1, 2021 Category: Neurology Source Type: research

Is Cerebral Amyloid- β Deposition Related to Post-stroke Cognitive Impairment?
AbstractApproximately two-thirds of ischemic stroke patients suffer from different levels of post-stroke cognitive impairment (PSCI),  but the underlying mechanisms of PSCI remain unclear. Cerebral amyloid-β (Aβ) deposition, a pathological hallmark of Alzheimer’s disease, has been discovered in the brains of stroke patients in some autopsy studies. However, less is known about the role of Aβ pathology in the development of  PSCI. It is hypothesized that cerebral ischemic injury may lead to neurotoxic Aβ accumulation in the brain, which further induces secondary neurodegeneration and...
Source: Translational Stroke Research - June 30, 2021 Category: Neurology Source Type: research

Carotid Plaque Vulnerability Assessed by Combined Shear Wave Elastography and Ultrafast Doppler Compared to Histology
AbstractUltrafast ultrasound imaging (UUI) provides an estimation of carotid plaque stiffness by shear wave elastography (SWE) and the quantification of wall shear stress (WSS) by ultrafast Doppler. We aimed to evaluate the combined criteria of plaque stiffness and WSS applied on the plaque as potential biomarkers of plaque vulnerability assessed by histology. We included patients for whom carotid endarterectomy had been decided by a multidisciplinary team. UUI was performed within 48  h before surgery, and acquisitions were obtained on a carotid longitudinal view. After endarterectomy, gross examination and histologi...
Source: Translational Stroke Research - June 28, 2021 Category: Neurology Source Type: research

SDF-1 α/CXCR4 Pathway Mediates Hemodynamics-Induced Formation of Intracranial Aneurysm by Modulating the Phenotypic Transformation of Vascular Smooth Muscle Cells
The objective of this study is to explore the role of the SDF-1 α/CXCR4 pathway in the development of intracranial aneurysm (IA) induced by hemodynamic forces. We collected 12 IA and six superficial temporal artery samples for high-throughput sequencing, hematoxylin and eosin staining, and immunohistochemistry to examine vascular remodeling and determine the ex pression of the components of the SDF-1α/CXCR4 pathway, structural proteins (α-SMA and calponin) of vascular smooth muscle cells (VSMCs), and inflammatory factors (MMP-2 and TNF-α). Computational fluid dynamics (CFD) was used for hemodynamic ...
Source: Translational Stroke Research - June 25, 2021 Category: Neurology Source Type: research

Neurological Instability in Ischemic Stroke: Relation with Outcome, Latency Time, and Molecular Markers
AbstractThe National Institutes of Health Stroke Scale (NIHSS) is commonly used to evaluate stroke neurological deficits and to predict the patient ’s outcome. Neurological instability (NI), defined as the variation of the NIHSS in the first 48 h, is a simple clinical metric that reflects dynamic changes in the area of the brain affected by the ischemia. We hypothesize that NI may represent areas of cerebral instability known as penumbra, wh ich could expand or reduce brain injury and its associated neurological sequels. In this work, our aim was to analyze the association of NI with the functional outcome at 3&...
Source: Translational Stroke Research - June 24, 2021 Category: Neurology Source Type: research

Characterization of CB2 Receptor Expression in Peripheral Blood Monocytes of Acute Ischemic Stroke Patients
AbstractBoth preclinical and clinical evidence supports the involvement of the endocannabinoid system in the pathobiology of cerebral ischemia. Selective cannabinoid-2 (CB2) receptor agonists exert significant neuroprotection in animal models of focal brain ischemia through a robust anti-inflammatory effect, involving both resident and peripheral immune cells. Nevertheless, no definitive studies demonstrating the relevance of CB2 receptors in human stroke exist.Using rtPCR and flow cytometry assays, we investigated CB2 receptor expression in circulating monocytes from 26 acute ischemic stroke patients and 16 age-matched he...
Source: Translational Stroke Research - June 18, 2021 Category: Neurology Source Type: research

A New Angiographic Collateral Grading System for Acute Basilar Artery Occlusion Treated with Endovascular Therapy
AbstractPoor clinical outcomes despite endovascular therapy (EVT) are common in patients with acute basilar artery occlusion (BAO). We aimed to develop a new angiographic collateral grading system for predicting 90-day functional outcomes of acute BAO after EVT. A prospectively registered consecutive cohort of acute BAO patients treated with EVT in our center during a 6-year period was reviewed. The angiographic collateral grading system for BAO (ACGS-BAO) included 4 grades for poor (grade 1 –2), intermediate (grade 3), and good (grade 4) collateral statuses. First, the independent association of ACGS-BAO with 90-day...
Source: Translational Stroke Research - June 18, 2021 Category: Neurology Source Type: research

Quantitative Corticospinal Tract Assessment in Acute Intracerebral Hemorrhage
AbstractIntracerebral hemorrhage (ICH) prognostication during the acute phase is often subjective among physicians and often affects treatment decisions. The present study explores objective imaging parameters using quantitative corticospinal tract (CST) fiber reconstruction during the acute phase of ICH and correlates these parameters with functional outcome and patient recovery. We prospectively enrolled nonsurgical spontaneous supratentorial ICH patients and obtained an MRI scan on day 5  ± 1. Q-space diffeomorphic reconstruction was performed using DSI Studio, and quantitative anisotropy (QA) was c...
Source: Translational Stroke Research - June 18, 2021 Category: Neurology Source Type: research

A System for Continuous Pre- to Post-reperfusion Intra-carotid Cold Infusion for Selective Brain Hypothermia in Rodent StrokeModels
AbstractIntra-carotid cold infusion (ICCI) appears as a promising method for hypothermia-mediated brain protection from ischemic stroke. Recent clinical pilot studies indicate easy implementation of ICCI into endovascular acute ischemic stroke treatment. Current rodent ICCI-in-stroke models limit ICCI to the post-reperfusion phase. To establish a method for continuous ICCI over the duration of intra-ischemia to post-reperfusion in rodent stroke models, a novel system was developed. Eighteen male Sprague-Dawley rats were included. Intraluminal filament method was used for transient middle cerebral artery occlusion (MCAO). N...
Source: Translational Stroke Research - June 18, 2021 Category: Neurology Source Type: research

Unruptured Giant Intracranial Aneurysms: Risk Factors for Mortality and Long-Term Outcome
This study aims to investigate the long-term outcomes of unruptured giant intracranial aneurysms (GIAs) with different treatment modalities and to analyze the factors affecting prognosis. We performed a retrospective medical record review of patients with unruptured GIAs treated at our institution from 2011 to 2018. Prognosis was compared to the best medical treatment without intervention (conservative treatment, CT) and surgical (ST) or endovascular (ET) treatment. Risk factors for mortality were investigated. A total of 276 patients were included in this study. Patients received CT in 16.3%, ST in 30.1%, and ET in 53.6% ...
Source: Translational Stroke Research - June 18, 2021 Category: Neurology Source Type: research

Wogonin Accelerates Hematoma Clearance and Improves Neurological Outcome via the PPAR- γ Pathway After Intracerebral Hemorrhage
In conclusion, our data suggest that wogonin facilitates hematoma clearance and neurobehavioral recovery by targeting PPAR-γ. (Source: Translational Stroke Research)
Source: Translational Stroke Research - June 18, 2021 Category: Neurology Source Type: research

Correction to: Phosphodiesterase 10A Inhibition Leads to Brain Region-Specific Recovery Based on Stroke Type
The original version of this article was revised due to retrospective Open Access. (Source: Translational Stroke Research)
Source: Translational Stroke Research - June 18, 2021 Category: Neurology Source Type: research

Correction to: Safety of Early Administration of Apixaban on Clinical Outcomes in Patients with Acute Large Vessel Occlusion
There was an error in Fig.  2d. The correct Fig. 2d is shown below. (Source: Translational Stroke Research)
Source: Translational Stroke Research - June 18, 2021 Category: Neurology Source Type: research

The Relationship of Morphological-Hemodynamic Characteristics, Inflammation, and Remodeling of Aneurysm Wall in Unruptured Intracranial Aneurysms
AbstractAneurysm wall remodeling (AWR) is an important pathological characteristic in aneurysm wall, which was characterized by abnormal histological structure and inflammation infiltration. In the present study, the aim is to determine the relationships of morphological-hemodynamic characteristics, inflammation, and AWR in intracranial aneurysms (IAs), as well as the pathological basis of morphological-hemodynamic predictors to achieve IA development. For this end, 113 unruptured IAs were prospectively collected from 110 cases. In addition, patient-specific computational fluid dynamics and geometry were adopted to determi...
Source: Translational Stroke Research - June 9, 2021 Category: Neurology Source Type: research

Natural Killer Cells Are Present in Rag1 −/− Mice and Promote Tissue Damage During the Acute Phase of Ischemic Stroke
AbstractRag1−/− mice, lacking functional B and T cells, have been extensively used as an adoptive transfer model to evaluate neuroinflammation in stroke research. However, it remains unknown whether natural killer (NK) cell development and functions are altered in Rag1−/− mice as well. This connection has been rarely discussed in previous studies but might have important implications for data interpretation. In contrast, the NOD-Rag1nullIL2rgnull (NRG) mouse model is devoid of NK cells and might therefore eliminate this potential shortcoming. Here, we compare immune-cell frequencies as well as pheno...
Source: Translational Stroke Research - June 8, 2021 Category: Neurology Source Type: research

Acute T2*-Weighted Magnetic Resonance Imaging Detectable Cerebral Thrombosis in a Rat Model of Subarachnoid Hemorrhage
AbstractSubarachnoid hemorrhage (SAH) is associated with a high incidence of morbidity and mortality, particularly within the first 72  h after aneurysm rupture. We recently found ultra-early cerebral thrombosis, detectable on T2* magnetic resonance imaging (MRI), in a mouse SAH model at 4 h after onset. The current study examined whether such changes also occur in rat at 24 h after SAH, the vessels involved, whether the degree of thrombosis varied with SAH severity and brain injury, and if it differed between male and female rats. Adult Sprague Dawley rats were subjected to an endovascular perforation SAH m...
Source: Translational Stroke Research - June 2, 2021 Category: Neurology Source Type: research

Zebrafish as a Model for In-Depth Mechanistic Study for Stroke
AbstractStroke is one of the world ’s leading causes of death and disability, posing enormous burden to the society. However, the pathogenesis and mechanisms that underlie brain injury and brain repair remain largely unknown. There’s an unmet need of in-depth mechanistic research in this field. Zebrafish (Danio rerio) is a powerful tool in brain science research mainly due to its small size and transparent body, high genome synteny with human, and similar nervous system structures. It can be used to establish both hemorrhagic and ischemic stroke models easily and effectively through different ways. After the es...
Source: Translational Stroke Research - May 29, 2021 Category: Neurology Source Type: research

Extracellular Vesicle Application as a Novel Therapeutic Strategy for Ischemic Stroke
AbstractIschemic stroke (IS) accounts for most of the cases of stroke onset, and due to short therapeutic time window for thrombolysis and numerous limited treatment measures and contraindications, lots of patients cannot receive satisfying therapeutic effects resulting in high disability and mortality worldly. In recent years, extracellular vesicles (EVs), as nanosized membrane-structured vesicles secreted from almost all cells, especially from stem/progenitor cells, have been reported to exert significant beneficial effects on IS from multiple approaches and notably ameliorate neurological outcome. Moreover, based on nan...
Source: Translational Stroke Research - May 13, 2021 Category: Neurology Source Type: research

Vascular Sema3E-Plexin-D1 Signaling Reactivation Promotes Post-stroke Recovery through VEGF Downregulation in Mice
In this study, using a mouse model of transient brain infarction, we aimed to investigate whether Sema3E-Plexin-D1 signaling was involved in cerebrovascular remodeling after ischemic injury. We found that ischemic damage rapidly inducedSema3e expression in the neurons of peri-infarct regions, followed by Plexin-D1 upregulation in remodeling vessels. Interestingly, Plexin-D1 reemergence was concurrent with brain vessels entering an active angiogenic process. In line with this,Plxnd1 ablation worsened neurological deficits, infarct volume, neuronal survival rate, and blood flow recovery. Furthermore, reduced and abnormal vas...
Source: Translational Stroke Research - May 12, 2021 Category: Neurology Source Type: research

Galectin-1 Contributes to Vascular Remodeling and Blood Flow Recovery After Cerebral Ischemia in Mice
AbstractGalectin-1 is found in the vasculature and has been confirmed to promote angiogenesis in several cancer models. Furthermore, galectin-1 has been demonstrated to improve the recovery of cerebral ischemia. However, whether vascular remodeling contributes to this improvement is still unknown. In the present study, photochemical cerebral ischemia was induced in both galectin-1-treated (2  μg/day,i.c.v, 3  days) and galectin-1 knockout mice. Laser speckle imaging and immunofluorescent staining demonstrated that circulation and vascular remodeling in the ischemic cortex were improved by galectin-1 treatment ...
Source: Translational Stroke Research - May 10, 2021 Category: Neurology Source Type: research

Carbonyl Reductase 1 Attenuates Ischemic Brain Injury by Reducing Oxidative Stress and Neuroinflammation
This study aims to observe the expression and role of carbonyl reductase 1 (CBR1), an NADPH-dependent oxidoreductase with specificity for carbonyl compounds such as 4-hydroxynonenal (4-HNE), in the brain after ischemic injury and to investigate the influence of CBR1 on ischemia-induced neuroinflammation. CBR1 expresses in the neurons, astrocyte, and microglia in the normal brain. The expression of CBR1 decreased in the ischemic regions following cerebral ischemia, and also reduced in primary neurons after OGD (oxygen-glucose deprivation); however, the expression of CBR1 significantly increased in microglia in the ischemic ...
Source: Translational Stroke Research - May 8, 2021 Category: Neurology Source Type: research

Hypocapnia Induced by Hyperventilation with Indocyanine Green Kinetics Detects the Effect of Staged Carotid Angioplasty to Avoid Hyperperfusion in Patients with Impaired Cerebral Hemodynamic Reserve
AbstractCerebral hyperperfusion syndrome (CHS) is a serious complication following carotid artery stenting (CAS). Staged angioplasty (AP) could potentially prevent CHS and hyperperfusion phenomenon (HPP) after revascularization. However, methods for measuring the effects of staged AP on cerebral hemodynamic reserve have not been established. Here, we evaluated whether indocyanine green kinetics and near-infrared spectroscopy (ICG-NIRS) with hypocapnia induced by hyperventilation can detect the effects of staged AP on hemodynamic reserve to prevent CHS after CAS. Participants comprised 44 patients at high risk of CHS, whose...
Source: Translational Stroke Research - May 6, 2021 Category: Neurology Source Type: research

Electrophilic and Drug-Induced Stimulation of NOTCH3 N-terminal Fragment Oligomerization in Cerebrovascular Pathology
AbstractSmall vessel disease is a prevalent age-related condition linked to increased risk of dementia and stroke. We investigate the most commonly inherited form, CADASIL, caused by cysteine-involving mutations inNOTCH3. Recent studies highlight accumulation of NOTCH3 N-terminal fragmentation product (NTF) in disease. In vitro, NTF is capable of both spontaneous and catecholamine-enhanced cysteine-mediated oligomerization. Despite well-characterized genetic influence on CADASIL, environmental effects, including medication usage, on disease remain unclear. We studied effects of assorted electrophilic compounds and drugs on...
Source: Translational Stroke Research - May 3, 2021 Category: Neurology Source Type: research

Targeted Temperature Management at 36  °C Shows Therapeutic Effectiveness via Alteration of Microglial Activation and Polarization After Ischemic Stroke
AbstractIschemic injury leads to cell death and inflammatory responses after stroke. Microglia especially play a crucial role in this brain inflammation. Targeted temperature management (TTM) at 33  °C has shown neuroprotective effects against many acute ischemic injuries. However, it has also shown some adverse effects in preclinical studies. Therefore, we explored the neuroprotective effect of TTM at 36 °C in the ischemic brain. To confirm the neuroprotective effects of hypothermia, mice were subjected to a permanent stroke and then treated with one of the TTM paradigms at 33 and 36 °C. For com...
Source: Translational Stroke Research - April 24, 2021 Category: Neurology Source Type: research

Delayed Recanalization —How Late Is Not Too Late?
AbstractStroke has become the second most prevalent cause of mortality in the world. Currently, the treatment of ischemic stroke is based on thrombolytic and thrombectomy therapy shortly after the ischemic event ( ≤ 4.5 h for thrombolytic strategies; ≤ 6 h for thrombectomy strategies). However, the majority of patients are unable to receive prompt treatment, particularly in undeveloped countries. Alternative solutions are lacking for those patients that miss the optimal window of opportunity for tre atment. Recently, new developments in imaging techniques and intravascular interventional devic...
Source: Translational Stroke Research - April 20, 2021 Category: Neurology Source Type: research

Diabetes Mellitus/Poststroke Hyperglycemia: a Detrimental Factor for tPA Thrombolytic Stroke Therapy
AbstractIntravenous administration of tissue-type plasminogen activator (IV tPA) therapy has long been considered a mainstay in ischemic stroke management. However, patients respond to IV tPA therapy unequally with some subsets of patients having worsened outcomes after treatment. In particular, diabetes mellitus (DM) is recognized as a clinically important vascular comorbidity that leads to lower recanalization rates and increased risks of hemorrhagic transformation (HT). In this short-review, we summarize the recent advances in understanding of the underlying mechanisms involved in post-IV tPA worsening of outcome in dia...
Source: Translational Stroke Research - April 20, 2021 Category: Neurology Source Type: research

The Role of Thrombin in Brain Injury After Hemorrhagic and Ischemic Stroke
AbstractThrombin is increased in the brain after hemorrhagic and ischemic stroke primarily due to the prothrombin entry from blood either with a hemorrhage or following blood-brain barrier disruption. Increasing evidence indicates that thrombin and its receptors (protease-activated receptors (PARs)) play a major role in brain pathology following ischemic and hemorrhagic stroke (including intracerebral, intraventricular, and subarachnoid hemorrhage). Thrombin and PARs affect brain injury via multiple mechanisms that can be detrimental or protective. The cleavage of prothrombin into thrombin is the key step of hemostasis and...
Source: Translational Stroke Research - April 20, 2021 Category: Neurology Source Type: research

Microglial Responses to Brain Injury and Disease: Functional Diversity and New Opportunities
This article reviews recent advances in our knowledge of microglia with emphases on molecular mediators of phenotype shifts and functional diversity. We describe microglia-targeted therapeutic opportunities, including pharmacologic modulation of phenotype and repopulation of the brain with fresh microglia. With the advent of powerful new tools, research on microglia has recently accelerated in pace and may translate into potential therapeutics against brain injury and neurological disease. (Source: Translational Stroke Research)
Source: Translational Stroke Research - April 20, 2021 Category: Neurology Source Type: research

Neutrophil Extracellular Traps may be a Potential Target for Treating Early Brain Injury in Subarachnoid Hemorrhage
In conclusion, NETs promoted neuroinflammation after SAH, while pharmacological inhibition of PAD4-NETs could reduce the inflammatory damage caused by SAH. These results supported the idea that NETs might be potential therapeutic targets for SAH. (Source: Translational Stroke Research)
Source: Translational Stroke Research - April 14, 2021 Category: Neurology Source Type: research