A Novel Mouse Model for Cerebral Venous Sinus Thrombosis
This study is aimed at developing a novel murine model suitable and relevant for evaluating injury patterns during CVST and studying its clinical aspects. CVST was achieved in C57BL/6J mice by autologous clot injection into the superior sagittal sinus (SSS) combined with bilateral ligation of external jugular veins. Clot was preparedex vivo using thrombin before injection. On days 1 and 7 after CVST, SSS occlusion and associated-parenchymal lesions were monitored using different modalities:in vivo real-time intravital microscopy, magnetic resonance imaging (MRI), and immuno-histology. In addition, mice were subjected to a ...
Source: Translational Stroke Research - March 5, 2021 Category: Neurology Source Type: research

Mesenchymal Stem Cell-Mediated Mitochondrial Transfer: a Therapeutic Approach for Ischemic Stroke
AbstractStroke is the leading cause of death and adult disability worldwide. Mitochondrial dysfunction is one of the hallmarks of stroke-induced neuronal death, and maintaining mitochondrial function is essential in cell survival and neurological progress following ischemic stroke. Stem cell-mediated mitochondrial transfer represents an emerging therapeutic approach for ischemic stroke. Accumulating evidence suggests that mesenchymal stem cells (MSCs) can directly transfer healthy mitochondria to damaged cells, and rescue mitochondrial damage-provoked tissue degeneration. This review summarizes the research on MSCs-mediate...
Source: Translational Stroke Research - March 3, 2021 Category: Neurology Source Type: research

Sex Differences in Cognitive Impairment Induced by Cerebral Microhemorrhage
AbstractIt has been suggested that cerebral microhemorrhages (CMHs) could be involved in cognitive decline. However, little is known about the sex-dependency of this effect. Using a multimodal approach combining behavioral tests, in vivo imaging, biochemistry, and molecular biology, we studied the cortical and hippocampal impact of a CMH in male and female mice (C57BL/6J) 6  weeks post-induction using a collagenase-induced model. Our work shows for the first time that a single cortical CMH exerts sex-specific effects on cognition. It notably induced visuospatial memory impairment in males only. This sex difference mig...
Source: Translational Stroke Research - March 3, 2021 Category: Neurology Source Type: research

Optogenetic Stimulation Reduces Neuronal Nitric Oxide Synthase Expression After Stroke
AbstractPost-stroke optogenetic stimulation has been shown to enhance neurovascular coupling and functional recovery. Neuronal nitric oxide synthase (nNOS) has been implicated as a key regulator of the neurovascular response in acute stroke; however, its role in subacute recovery remains unclear. We investigated the expression of nNOS in stroke mice undergoing optogenetic stimulation of the contralesional lateral cerebellar nucleus (cLCN). We also examined the effects of nNOS inhibition on functional recovery using a pharmacological inhibitor targeting nNOS. Optogenetically stimulated stroke mice demonstrated significant i...
Source: Translational Stroke Research - March 3, 2021 Category: Neurology Source Type: research

Analysis of Treatment Outcome After Endovascular Treatment in Different Pathological Subtypes of Basilar Artery Occlusion: a Single Center Experience
AbstractThe current study aimed to evaluate whether patients with different pathologic subtypes of basilar artery occlusion (BAO) stroke could affect the clinical outcome after receiving endovascular treatment(EVT). A total of 187 consecutive patients with acute BAO receiving endovascular treatment (EVT) from January 2012 to July 2018 at the Beijing Tiantan Hospital were recruited in this study. The patients were categorized into three groups: embolism without vertebral artery (VA) steno-occlusion (group 1), in situ atherosclerotic thrombosis (group 2), and embolism from tandem VA steno-occlusion (group 3). Among the 187 p...
Source: Translational Stroke Research - March 3, 2021 Category: Neurology Source Type: research

Carotid Endarterectomy and Stenting in a Chinese Population: Safety Outcome of the Revascularization of Extracranial Carotid Artery Stenosis Trial
AbstractCarotid endarterectomy (CEA) and carotid artery stenting (CAS) have been well-established as two effective treatment modalities for carotid artery stenosis, while their clinical outcomes in real-world China are still unknown due to lack of nationwide trials. We aimed to evaluate the safety outcome profile of CEA and CAS in Chinese patients with carotid artery stenosis. The Revascularization of Extracranial Carotid Artery Stenosis trial was a multicentre, prospective cohort study of CEA or CAS in treating patients with carotid artery stenosis. We included symptomatic or asymptomatic patients with carotid artery sten...
Source: Translational Stroke Research - March 3, 2021 Category: Neurology Source Type: research

Efficacy and Safety of Intravenous rtPA in Ischemic Strokes Due to Small-Vessel Occlusion: Systematic Review and Meta-Analysis
AbstractIntravenous recombinant tissue plasminogen activator (iv-rtPA) has been routinely used to treat ischemic stroke for 25  years, following large clinical trials. However, there are few prospective studies on the efficacy and safety of this therapy in strokes attributed to cerebral small vessel disease (SVD). We evaluated functional outcome (modified Rankin scale, mRS) and symptomatic intracerebral hemorrhage (sICH) u sing all available data on the effects of iv-rtPA in SVD-related ischemic stroke (defined either using neuroimaging, clinical features, or both). Using fixed-effect and random-effects models, we cal...
Source: Translational Stroke Research - February 28, 2021 Category: Neurology Source Type: research

Ten Years and Counting: a Celebration of the 10th Anniversary of Translational Stroke Research
(Source: Translational Stroke Research)
Source: Translational Stroke Research - February 27, 2021 Category: Neurology Source Type: research

White Matter Free Water is a Composite Marker of Cerebral Small Vessel Degeneration
AbstractTo investigate the association between white matter free water (FW) and common imaging markers of cerebral small vessel diseases (CSVD) in two groups of subjects with different clinical status. One hundred and forty-four community subjects (mean age 60.5) and 84 CSVD subjects (mean age 61.2) were retrospectively included in the present study. All subjects received multi-modal magnetic resonance imaging and clinical assessments. The association between white matter FW and common CSVD imaging markers, including white matter hyperintensities (WMH), dilated perivascular space (PVS), lacunes, and microbleeds, were asses...
Source: Translational Stroke Research - February 25, 2021 Category: Neurology Source Type: research

Neurovascular Units and Neural-Glia Networks in Intracerebral Hemorrhage: from Mechanisms to Translation
AbstractIntracerebral hemorrhage (ICH), the most lethal type of stroke, often leads to poor outcomes in the clinic. Due to the complex mechanisms and cell –cell crosstalk during ICH, the neurovascular unit (NVU) was proposed to serve as a promising therapeutic target for ICH research. This review aims to summarize the development of pathophysiological shifts in the NVU and neural–glia networks after ICH. In addition, potential targets for ICH ther apy are discussed in this review. Beyond cerebral blood flow, the NVU also plays an important role in protecting neurons, maintaining central nervous system (CNS) hom...
Source: Translational Stroke Research - February 24, 2021 Category: Neurology Source Type: research

The Key Regulator of Necroptosis, RIP1 Kinase, Contributes to the Formation of Astrogliosis and Glial Scar in Ischemic Stroke
AbstractNecroptosis initiation relies on the receptor-interacting protein 1 kinase (RIP1K). We recently reported that genetic and pharmacological inhibition of RIP1K produces protection against ischemic stroke-induced astrocytic injury. However, the role of RIP1K in ischemic stroke-induced formation of astrogliosis and glial scar remains unknown. Here, in a transient middle cerebral artery occlusion (tMCAO) rat model and an oxygen and glucose deprivation and reoxygenation (OGD/Re)-induced astrocytic injury model, we show that RIP1K was significantly elevated in the reactive astrocytes. Knockdown of RIP1K or delayed adminis...
Source: Translational Stroke Research - February 24, 2021 Category: Neurology Source Type: research

CYP2C19 Loss-of-Function Associated with First-Time Ischemic Stroke in Non-surgical Asymptomatic Carotid Artery Stenosis During Clopidogrel Therapy
This study measures effect ofCYP2C19 genotype on ischemic stroke risk during clopidogrel therapy for asymptomatic, extracranial carotid stenosis patients. Using deidentified electronic health records, patients were selected for retrospective cohort using administrative code for carotid stenosis, availability ofCYP2C19 genotype result, clopidogrel exposure, and established patient care. Patients with intracranial atherosclerosis, aneurysm, arteriovenous malformation, prior ischemic stroke, or observation time
Source: Translational Stroke Research - February 21, 2021 Category: Neurology Source Type: research

Short-term glycemic variability and hemorrhagic transformation after successful endovascular thrombectomy
ConclusionsTime-related GV during the first 36 h after successful ERT has a stronger correlation with sICH and poor functional outcomes compared to any GV parameters. This suggests that maintaining stable glucose may be an important factor in the prevention of sICH after undergoing successful ERT. (Source: Translational Stroke Research)
Source: Translational Stroke Research - February 12, 2021 Category: Neurology Source Type: research

Imaging-Based Outcome Prediction of Acute Intracerebral Hemorrhage
AbstractWe hypothesized that imaging-only-based machine learning algorithms can analyze non-enhanced CT scans of patients with acute intracerebral hemorrhage (ICH). This retrospective multicenter cohort study analyzed 520 non-enhanced CT scans and clinical data of patients with acute spontaneous ICH. Clinical outcome at hospital discharge was dichotomized into good outcome and poor outcome using different modified Rankin Scale (mRS) cut-off values. Predictive performance of a random forest machine learning approach based on filter- and texture-derived high-end image features was evaluated for differentiation of functional ...
Source: Translational Stroke Research - February 6, 2021 Category: Neurology Source Type: research

Inhibition of Dectin-1 Ameliorates Neuroinflammation by Regulating Microglia/Macrophage Phenotype After Intracerebral Hemorrhage in Mice
In conclusion, our data suggest that Dectin-1 is involved in the microglia/macrophage polarization and functional recovery after ICH, and that this mechanism, at least in part, may contribute to the involvement of the Syk/Car d9/NF-kB pathway. (Source: Translational Stroke Research)
Source: Translational Stroke Research - February 4, 2021 Category: Neurology Source Type: research

Mechanical Thrombectomy in Nonagenarians: a Systematic Review and Meta-analysis
AbstractThis systematic review and meta-analysis aimed to summarize the current literature on mechanical thrombectomy (MT) in nonagenarians and to provide updated clinical evidence of its feasibility, effectiveness, and safety in nonagenarians. PubMed, EMBASE, the Cochrane Library, and Web of Science were searched for relevant randomized controlled trials and observational studies that reported the clinical outcomes of nonagenarians with acute ischemic stroke after undergoing mechanical thrombectomy. Risk of bias was assessed using different scales.I2 statistic was used to evaluate the heterogeneity of the results, while m...
Source: Translational Stroke Research - February 2, 2021 Category: Neurology Source Type: research

Immune Cell Infiltration into the Brain After Ischemic Stroke in Humans Compared to Mice and Rats: a Systematic Review and Meta-Analysis
AbstractAlthough several studies have suggested that anti-inflammatory strategies reduce secondary infarct growth in animal stroke models, clinical studies have not yet demonstrated a clear benefit of immune modulation in patients. Potential reasons include systematic differences of post-ischemic neuroinflammation between humans and rodents. We here performed a systematic review and meta-analysis to summarize and compare the spatial and temporal distribution of immune cell infiltration in human and rodent stroke. Data on spatiotemporal distribution of immune cells (T cells, macrophages, and neutrophils) and infarct volume ...
Source: Translational Stroke Research - January 26, 2021 Category: Neurology Source Type: research

Clinical Value of 3D-Printed Navigation Technology Combined with Neuroendoscopy for Intracerebral Hemorrhage
In conclusion, 3D-printed navigation technology used for the neuroendoscopic hematoma removal is a more reliable and less invasive approach in the treatment of IC H. This technique has great application prospects and deserves promotion in the future clinical practice. (Source: Translational Stroke Research)
Source: Translational Stroke Research - January 25, 2021 Category: Neurology Source Type: research

Endoplasmic Reticulum Interaction Supports Energy Production and Redox Homeostasis in Mitochondria Released from Astrocytes
In this study, we investigated the molecular mechanisms that underlie mitochondria secretion, redox status, and functional regulation in the extracellular environment. Exposure of rat primary astrocytes to NAD or cADPR elicited an increase in mitochondrial calcium through ryanodine receptor (RyR) in the endoplasmic reticulum (ER). Importantly, CD38 stimulation with NAD accelerated ATP production along with increasing glutathione reductase (GR) and dipicolinic acid (DPA) in intracellular mitochondria. When RyR was blocked by Dantrolene, all effects were clearly diminished. Mitochondrial functional assay showed that these ac...
Source: Translational Stroke Research - January 21, 2021 Category: Neurology Source Type: research

A Review of Translational Magnetic Resonance Imaging in Human and Rodent Experimental Models of Small Vessel Disease
AbstractCerebral small vessel disease (SVD) is a major health burden, yet the pathophysiology remains poorly understood with no effective treatment. Since much of SVD develops silently and insidiously, non-invasive neuroimaging such as MRI is fundamental to detecting and understanding SVD in humans. Several relevant SVD rodent models are established for which MRI can monitor in vivo changes over time prior to histological examination. Here, we critically review the MRI methods pertaining to salient rodent models and evaluate synergies with human SVD MRI methods. We found few relevant publications, but argue there is consid...
Source: Translational Stroke Research - January 12, 2021 Category: Neurology Source Type: research

TRPM7 Mediates Neuronal Cell Death Upstream of Calcium/Calmodulin-Dependent Protein Kinase II and Calcineurin Mechanism in Neonatal Hypoxic-Ischemic Brain Injury
In this study, we employed a mouse model of hypoxic-ischemic brain cell death which mimics the pathophysiology of hypoxic-ischemic encephalopathy (HIE). HIE is a major public health issue and an important cause of neonatal deaths worldwide; however, the available treatments for HIE remain limited. Its survivors face life-long neurological challenges including mental retardation, cerebral palsy, epilepsy and seizure disorders, motor impairments, and visual and auditory impairments. Through a proteomic analysis, we identified calcium/calmodulin-dependent protein kinase II (CaMKII) and phosphatase calcineurin as potential med...
Source: Translational Stroke Research - January 12, 2021 Category: Neurology Source Type: research

Combined Perfusion and Permeability Imaging Reveals Different Pathophysiologic Tissue Responses After Successful Thrombectomy
AbstractDespite successful recanalization of large-vessel occlusions in acute ischemic stroke, individual patients profit to a varying degree. Dynamic susceptibility-weighted perfusion and dynamic T1-weighted contrast-enhanced blood-brain barrier permeability imaging may help to determine secondary stroke injury and predict clinical outcome. We prospectively performed perfusion and permeability imaging in 38 patients within 24  h after successful mechanical thrombectomy of an occlusion of the middle cerebral artery M1 segment. Perfusion alterations were evaluated on cerebral blood flow maps, blood-brain barrier disrup...
Source: Translational Stroke Research - January 11, 2021 Category: Neurology Source Type: research

Attenuation of the Induction of TLRs 2 and 4 Mitigates Inflammation and Promotes Neurological Recovery After Focal Cerebral Ischemia
In this study, we further examined the effect of unsuppressed induction of TLRs 2 and 4 on the expression of its downstream signaling molecules and pro-inflammatory cytokines 1  week after reperfusion. The primary purpose of this study was to investigate the effect of simultaneous knockdown of TLRs 2 and 4 on M1/M2 microglial polarization dynamics and post-stroke neurological deficits and the recovery. Transient focal cerebral ischemia was induced in young adult male Spra gue-Dawley rats by the middle cerebral artery occlusion (MCAO) procedure using a monofilament suture. Appropriate cohorts of rats were treated with ...
Source: Translational Stroke Research - January 11, 2021 Category: Neurology Source Type: research

Higher Plasma Osteopontin Concentrations Associated with Subsequent Development of Chronic Shunt-Dependent Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage
AbstractA matricellular protein osteopontin (OPN) is considered to exert neuroprotective and healing effects on neurovascular injuries in an acute phase of aneurysmal subarachnoid hemorrhage (SAH). However, the relationships between OPN expression and chronic shunt-dependent hydrocephalus (SDHC) have never been investigated. In 166 SAH patients (derivation and validation cohorts, 110 and 56, respectively), plasma OPN levels were serially measured at days1 −3, 4−6, 7−9, and 10−12 after aneurysmal obliteration. The OPN levels and clinical factors were compared between patients with and without subsequ...
Source: Translational Stroke Research - January 9, 2021 Category: Neurology Source Type: research

Treatment with Atorvastatin During Vascular Remodeling Promotes Pericyte-Mediated Blood-Brain Barrier Maturation Following Ischemic Stroke
This study examined our hypothesis that, during vascular remodeling after stroke, treatment with atorvastatin could facilitate BBB maturation in remodeling vasculature in ischemic brain. Adult spontaneously hypertensive rats underwent middle cerebral artery occlusion with reperfusion (MCAO/RP). Atorvastatin, at dose of 3  mg/kg, was delivered daily starting at 14 days after MCAO/RP onset for 7 days. The rats were studied at multiple time points up to 8 weeks with multimodal-MRI, behavior tests, immunohistochemistry, and biochemistry. The delayed treatment of atorvastatin significantly reduced infarct si...
Source: Translational Stroke Research - January 9, 2021 Category: Neurology Source Type: research

Recanalization Therapy for Acute Ischemic Stroke with Large Vessel Occlusion: Where We Are and What Comes Next?
AbstractIn the past 5  years, the success of multiple randomized controlled trials of recanalization therapy with endovascular thrombectomy has transformed the treatment of acute ischemic stroke with large vessel occlusion. The evidence from these trials has now established endovascular thrombectomy as standard of care. This review will discuss the chronological evolution of large vessel occlusion treatment from early medical therapy with tissue plasminogen activator to the latest mechanical thrombectomy. Additionally, it will highlight the potential areas in endovascular thrombectomy for acute ischemic stroke ope n t...
Source: Translational Stroke Research - January 6, 2021 Category: Neurology Source Type: research

Tocilizumab Reduces Vasospasms, Neuronal Cell Death, and Microclot Formation in a Rabbit Model of Subarachnoid Hemorrhage
AbstractEarly brain injury (EBI), delayed cerebral vasospasm (DCVS), and delayed cerebral ischemia (DCI) are common complications of subarachnoid hemorrhage (SAH). Inflammatory processes in the cerebrospinal fluid (CSF) are one of the causes for such complications. Our aim to study the effects of an IL-6 receptor antagonist (Tocilizumab) examines the occurrence of DCVS, neuronal cell death, and microclot formation in an acute SAH rabbit model. Twenty-nine New Zealand white rabbits were randomized into one of three groups as the SAH, SAH + Tocilizumab, and sham groups. In SAH groups, hemorrhage was induced by extracranial-i...
Source: Translational Stroke Research - January 6, 2021 Category: Neurology Source Type: research

Reparative System Arising from CCR2(+) Monocyte Conversion Attenuates Neuroinflammation Following Ischemic Stroke
In this study of transgenic mice with functional CX3CR1GFP/+ or CX3CR1GFP/+-CCR2RFP/+, we found that CCR2highCX3CR1low monocytes recruited to the injured brain were cytokine-dependently converted into CCR2lowCX3CR1high macrophages, especially under the influence of IL-4 and IL-13, thereby attenuating the neuroinflammation following sterile ischemic stroke. The overall data suggest that (1) the regulation of monocyte-switching is one of the ultimate reparative strategies in ischemic stroke, and (2) the adaptation of monocytes in a locally inflamed milieu is vital to alleviating the effects of ischemic stroke through innate ...
Source: Translational Stroke Research - January 6, 2021 Category: Neurology Source Type: research

Neuroprotection by Remote Ischemic Conditioning in Rodent Models of Focal Ischemia: a Systematic Review and Meta-Analysis
AbstractRemote ischemic conditioning (RIC) is a promising neuroprotective therapy for ischemic stroke. Preclinical studies investigating RIC have shown RIC reduced infarct volume, but clinical trials have been equivocal. Therefore, the efficacy of RIC in reducing infarct volume and quality of current literature needs to be evaluated to identify knowledge gaps to support future clinical trials. We performed a systematic review and meta-analysis of preclinical literature involving RIC in rodent models of focal ischemia. This review was registered with PROSPERO (CRD42019145441). Eligibility criteria included rat or mice model...
Source: Translational Stroke Research - January 6, 2021 Category: Neurology Source Type: research

Acute and Chronic Kidney Dysfunction and Outcome After Stroke Thrombectomy
AbstractData on the impact of kidney dysfunction on outcome in patients with stroke due to large vessel occlusion are scarce. The few available studies are limited by only considering single kidney parameters measured at one time point. We thus investigated the influence of both chronic kidney disease (CKD) and acute kidney injury (AKI) on outcome after mechanical thrombectomy. We included consecutive patients with anterior circulation large vessel occlusion stroke receiving mechanical thrombectomy at our center over an 8-year period. We extracted clinical data from a prospective registry and investigated kidney serum para...
Source: Translational Stroke Research - January 4, 2021 Category: Neurology Source Type: research

The Left Atrial Septal Pouch: A New Stroke Risk Factor?
We examined transesophageal echocardiograms (TEEs) performed between July 2011 and December 2018. LASP prevalence was determined in TEEs referred for ischemic stroke or transient ischemic attack ( “stroke”) and compared with LASP prevalence in patients undergoing TEEs for other reasons (“non-stroke”). Stroke subtyping was performed using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. There were 306 TEEs from 144 non-stroke and 162 stroke patients. Mean age and sex distribution were 56 ± 1 (mean ± SE) and 65% male in the non-stroke group and 58 &...
Source: Translational Stroke Research - January 4, 2021 Category: Neurology Source Type: research

Robotic Assessment of Upper Limb Function in a Nonhuman Primate Model of Chronic Stroke
AbstractStroke is a leading cause of death and disability worldwide and survivors are frequently left with long-term disabilities that diminish their autonomy and result in the need for chronic care. There is an urgent need for the development of therapies that improve stroke recovery, as well as accurate and quantitative tools to measure function. Nonhuman primates closely resemble humans in neuroanatomy and upper limb function and may be crucial in randomized pre-clinical trials for testing the efficacy of stroke therapies. To test the feasibility of robotic assessment of motor function in a NHP model of stroke, two cyno...
Source: Translational Stroke Research - January 3, 2021 Category: Neurology Source Type: research

Stability Assessment of Intracranial Aneurysms Using Machine Learning Based on Clinical and Morphological Features
AbstractMachine learning (ML) as a novel approach could help clinicians address the challenge of accurate stability assessment of unruptured intracranial aneurysms (IAs). We developed multiple ML models for IA stability assessment and compare their performances. We enrolled 1897 consecutive patients with unstable (n = 528) and stable (n = 1539) IAs. Thirteen patient-specific clinical features and eighteen aneurysm morphological features were extracted to generate support vector machine (SVM), random forest (RF), and feed-forward artificial neural network (ANN) models. The discriminatory performa...
Source: Translational Stroke Research - October 20, 2020 Category: Neurology Source Type: research

Effectiveness of Adding Antiplatelets to Oral Anticoagulants in Patients with Acute Ischemic Stroke with Atrial Fibrillation and Concomitant Large Artery Steno-Occlusion
In conclusion, OAC + AP might increase the risk of 3-month outcome ev ents compared with OAC alone in patients with AIS with AF and concomitant LASO. However, the effect of additional AP to OAC might differ according to LASO type. (Source: Translational Stroke Research)
Source: Translational Stroke Research - October 20, 2020 Category: Neurology Source Type: research

Aneurysmal Subarachnoid Hemorrhage: the Last Decade
AbstractAneurysmal subarachnoid hemorrhage (SAH) affects six to nine people per 100,000 per year, has a 35% mortality, and leaves many  with lasting disabilities, often related to cognitive dysfunction. Clinical decision rules and more sensitive computed tomography (CT) have made the diagnosis of SAH easier, but physicians must maintain a high index of suspicion. The management of these patients is based on a limited number of ran domized clinical trials (RCTs). Early repair of the ruptured aneurysm by endovascular coiling or neurosurgical clipping is essential, and coiling is superior to clipping in cases amenable to...
Source: Translational Stroke Research - October 19, 2020 Category: Neurology Source Type: research

Uric Acid and Gluconic Acid as Predictors of Hyperglycemia and Cytotoxic Injury after Stroke
AbstractHyperglycemia is a feature of worse brain injury after acute ischemic stroke, but the underlying metabolic changes and the link to cytotoxic brain injury are not fully understood. In this observational study, we applied regression and machine learning classification analyses to identify metabolites associated with hyperglycemia and a neuroimaging proxy for cytotoxic brain injury. Metabolomics and lipidomics were carried out using liquid chromatography-tandem mass spectrometry in admission plasma samples from 381 patients presenting with an acute stroke. Glucose was measured by a central clinical laboratory, and a s...
Source: Translational Stroke Research - October 17, 2020 Category: Neurology Source Type: research

Combination of Polyethylene Glycol-Conjugated Urokinase Nanogels and Urokinase for Acute Ischemic Stroke Therapeutic Implications
AbstractTissue reperfusion is a serious therapeutic strategy of ischemic stroke in addition to recanalization. In this work, we aimed to establish new urokinase-based therapeutics in order to dissolve large vessel thrombus together with microthrombi for stroke implications. Formulations consisted of free urokinase (UK), polyethylene glycol –crosslinked urokinase nanogel (PEG-UK), and a 1:1 mixture of UK and PEG-UK (PEG-UK+UK) were tested both in vitro and in vivo. In vitro experiments confirmed the pH-dependent release of PEG-UK in the PEG-UK+UK formulation. It was activated at pH 6.50, an environmental pH in th...
Source: Translational Stroke Research - October 16, 2020 Category: Neurology Source Type: research

Disruptions of Anaerobic Gut Bacteria Are Associated with Stroke and Post-stroke Infection: a Prospective Case –Control Study
AbstractIn recent years, preclinical studies have illustrated the potential role of intestinal bacterial composition in the risk of stroke and post-stroke infections. The results of these studies suggest that bacteria capable of producing volatile metabolites, including trimethylamine-N-oxide (TMAO) and butyrate, play opposing, yet important roles in the cascade of events leading to stroke. However, no large-scale studies have been undertaken to determine the abundance of these bacterial communities in stroke patients and to assess the impact of disrupted compositions of the intestinal microbiota on patient outcomes. In th...
Source: Translational Stroke Research - October 14, 2020 Category: Neurology Source Type: research

Correction to: Activation of Sigma-1 Receptor Enhanced Pericyte Survival Via the Interplay between Apoptosis and Autophagy: Implications for Blood –Brain Barrier Integrity in Stroke
In the original publication of this article, the representative western blot images of β-actin in Fig. 3e was presented repeatedly in Fig. 7b due to the same set of samples isolated from tissue of WT and σ-1R KO treated with pMCAO. (Source: Translational Stroke Research)
Source: Translational Stroke Research - October 10, 2020 Category: Neurology Source Type: research

Folic Acid Deficiency Enhances the Tyr705 and Ser727 Phosphorylation of Mitochondrial STAT3 in In Vivo and In Vitro Models of Ischemic Stroke
AbstractIschemic stroke remains one of the most common causes of death and disability worldwide. The stroke patients with an inadequate intake of folic acid tend to have increased brain injury and poorer prognosis. However, the precise mechanisms underlying the harmful effects of folic acid deficiency (FD) in ischemic stroke is still elusive. Here, we aimed to test the hypothesis that mitochondrial localized STAT3 (mitoSTAT3) expression may be involved in the process of neuronal damage induced by FD in in vivo and in vitro models of ischemic stroke. Our results exhibited that FD increased infarct size and aggravated the da...
Source: Translational Stroke Research - October 10, 2020 Category: Neurology Source Type: research

Autologous Mesenchymal Stem Cells Improve Motor Recovery in Subacute Ischemic Stroke: a Randomized Clinical Trial
AbstractWhile preclinical stroke studies have shown that mesenchymal stem cells (MSCs) promote recovery, few randomized controlled trials (RCT) have assessed cell therapy in humans. In this RCT, we assessed the safety, feasibility, and efficacy of intravenous autologous bone marrow-derived MSCs in subacute stroke. ISIS-HERMES was a single-center, open-label RCT, with a 2-year follow-up. We enrolled patients aged 18 –70 years less than 2 weeks following moderate-severe ischemic carotid stroke. Patients were randomized 2:1 to receive intravenous MSCs or not. Primary outcomes assessed feasibility and safety. S...
Source: Translational Stroke Research - September 10, 2020 Category: Neurology Source Type: research

Predictors of Successful First-Pass Thrombectomy with a Balloon Guide Catheter: Results of a Decision Tree Analysis
AbstractComplete recanalization after a single retrieval maneuver is an interventional goal in acute ischemic stroke and an independent factor for good clinical outcome. Anatomical biomarkers for predicting clot removal difficulties have not been comprehensively analyzed and await unused. We retrospectively evaluated 200 consecutive patients who suffered acute stroke and occlusion of the anterior circulation and were treated with mechanical thrombectomy through a balloon guide catheter (BGC). The primary objective was to evaluate the influence of carotid tortuosity and BGC positioning on the one-pass Modified Thrombolysis ...
Source: Translational Stroke Research - September 10, 2020 Category: Neurology Source Type: research

Predictors and Outcomes of Neurological Deterioration in Intracerebral Hemorrhage: Results from the TICH-2 Randomized Controlled Trial
AbstractNeurological deterioration is common after intracerebral hemorrhage (ICH). We aimed to identify the predictors and effects of neurological deterioration and whether tranexamic acid reduced the risk of neurological deterioration. Data from the Tranexamic acid in IntraCerebral Hemorrhage-2 (TICH-2) randomized controlled trial were analyzed. Neurological deterioration was defined as an increase in National Institutes of Health Stroke Scale (NIHSS) of ≥ 4 or a decline in Glasgow Coma Scale of ≥ 2. Neurological deterioration was considered to be early if it started ≤ 48 h and late if c...
Source: Translational Stroke Research - September 8, 2020 Category: Neurology Source Type: research

Iodinated Contrast Agents Reduce the Efficacy of Intravenous Recombinant Tissue-Type Plasminogen Activator in Acute Ischemic Stroke Patients: a Multicenter Cohort Study
This study aimed to investigate whether the application of iodinated contrast agents before intravenous (IV) recombinant tissue plasminogen activator (rt-PA) reduces the efficacy in acute ischemic stroke (AIS) patients. To determine whether the application of iodinated contrast agents before intravenous rt-PA reduces the efficacy in AIS patients. We analyzed our prospectively collected data of consecutive AIS patients receiving IV rt-PA treatment in the MISSION CHINA study. Clinical outcome at 3  months was assessed with modified Rankin Scale (mRS) score and dichotomized into good outcome (0–2) and poor outcome ...
Source: Translational Stroke Research - September 7, 2020 Category: Neurology Source Type: research

Cerebral Small Vessel Disease Influences Hippocampal Subfield Atrophy in Mild Cognitive Impairment
AbstractTo investigate patterns of hippocampal subfield atrophy among patients with amnestic mild cognitive impairment, stratified by severity of small vessel disease (SVD) and corresponding associations with cognitive domains. One hundred seventy-six MCI subjects (mean age  = 65.56 years, SD = 8.77) underwent neuropsychological assessments and magnetic resonance imaging. SVD was rated 0 (no SVD), 1 (mild SVD) and 2 (moderate to severe SVD) based on load of white matter hyperintensities (WMH) and lacunes. Demographics, cerebrovascular risk factors, grey and wh ite matter volumes and hippoca...
Source: Translational Stroke Research - September 6, 2020 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 w...
Source: Translational Stroke Research - August 31, 2020 Category: Neurology Source Type: research

TREM-1 Exacerbates Neuroinflammatory Injury via NLRP3 Inflammasome-Mediated Pyroptosis in Experimental Subarachnoid Hemorrhage
In conclusion, our results revealed the critical role of TREM-1 in neuroinflammation following SAH, suggesting that TREM-1 inhibition might be a potential therapeutic approach for SAH. (Source: Translational Stroke Research)
Source: Translational Stroke Research - August 29, 2020 Category: Neurology Source Type: research

Neurogenesis After Stroke: A Therapeutic Perspective
AbstractStroke is a major cause of death and disability worldwide. Yet therapeutic strategies available to treat stroke are very limited. There is an urgent need to develop novel therapeutics that can effectively facilitate functional recovery. The injury that results from stroke is known to induce neurogenesis in penumbra of the infarct region. There is considerable interest in harnessing this response for therapeutic purposes. This review summarizes what is currently known about stroke-induced neurogenesis and the factors that have been identified to regulate it. Additionally, some key studies in this field have been hig...
Source: Translational Stroke Research - August 28, 2020 Category: Neurology Source Type: research

Safety of Early Administration of Apixaban on Clinical Outcomes in Patients with Acute Large Vessel Occlusion
AbstractEarly administration of direct oral anticoagulants in patients with acute large vessel occlusion (LVO) and nonvalvular atrial fibrillation (NVAF) is a concern, as endovascular therapy (EVT) became highly utilized. We conducted a historical and prospective multicenter registry at 38 centers in Japan from July 2016 to February 2018. Patients aged ≥ 20 years with NVAF and acute LVO or stenosis who received apixaban within 14 days from onset were included. We compared patients who received apixaban
Source: Translational Stroke Research - August 6, 2020 Category: Neurology Source Type: research

Left Atrial Appendage Closure for Patients with Cerebral Amyloid Angiopathy and Atrial Fibrillation: the LAA-CAA Cohort
AbstractAnticoagulation increases the risk of intracerebral hemorrhage (ICH) in patients with cerebral amyloid angiopathy (CAA), so the management of stroke-risk in patients with both atrial fibrillation (AF) and CAA is controversial. Advances in left atrial appendage closure (LAAC) techniques provide a stroke-risk-reduction option which avoids long-term oral anticoagulation (OAC). We aimed to evaluate the safety of this intervention in patients with CAA. This is an observational cohort study of patients with severe CAA (with or without ICH) and AF who were treated with LAA closure. The Watchman ™ and Amulet® LAA...
Source: Translational Stroke Research - August 6, 2020 Category: Neurology Source Type: research