Effects of New-Generation Antiepileptic Drug Prophylaxis on Delayed Neurovascular Events After Aneurysmal Subarachnoid Hemorrhage
AbstractNeuroelectric disruptions such as seizures and cortical spreading depolarization may contribute to the development of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH). However, effects of antiepileptic drug prophylaxis on outcomes remain controversial in SAH. The authors investigated if prophylactic administration of new-generation antiepileptic drugs levetiracetam and perampanel was beneficial against delayed neurovascular events after SAH. This was a retrospective single-center cohort study of 121 consecutive SAH patients including 56 patients of admission World Federation of Neurolo...
Source: Translational Stroke Research - November 5, 2022 Category: Neurology Source Type: research

Gas6 Promotes Microglia Efferocytosis and Suppresses Inflammation Through Activating Axl/Rac1 Signaling in Subarachnoid Hemorrhage Mice
AbstractEarly brain injury (EBI) following   subarachnoid hemorrhage (SAH) is characterized by rapid development of neuron apoptosis and dysregulated inflammatory response. Microglia efferocytosis plays a critical role in the clearance of apoptotic cells, attenuation of inflammation, and minimizing brain injury in various pathological con ditions. Here, using a mouse SAH model, we aim to investigate whether microglia efferocytosis is involved in post-SAH inflammation and to determine the underlying signaling pathway. We hypothesized that TAM receptors and their ligands regulate this process. To prove our hypothesis, the...
Source: Translational Stroke Research - November 3, 2022 Category: Neurology Source Type: research

Deferoxamine Prevents Neonatal Posthemorrhagic Hydrocephalus Through Choroid Plexus-Mediated Iron Clearance
AbstractPosthemorrhagic hydrocephalus occurs in up to 30% of infants with high-grade intraventricular hemorrhage and is associated with the worst neurocognitive outcomes in preterm infants. The mechanisms of posthemorrhagic hydrocephalus after intraventricular hemorrhage are unknown; however, CSF levels of iron metabolic pathway proteins including hemoglobin have been implicated in its pathogenesis. Here, we develop an animal model of intraventricular hemorrhage using intraventricular injection of hemoglobin at post-natal day 4 that results in acute and chronic  hydrocephalus, pathologic choroid plexus iron accumulation, ...
Source: Translational Stroke Research - October 29, 2022 Category: Neurology Source Type: research

Monocyte-to-Lymphocyte Ratio in Clot Analysis as a Marker of Cardioembolic Stroke Etiology
AbstractThe aim of the study was to find markers of high-risk cardioembolic etiology (HRCE) in patients with cryptogenic strokes (CS) through the analysis of intracranial clot by flow cytometry (FC). A prospective single-center study was designed including patients with large vessel occlusion strokes. The percentage of granulocytes, monocytes, lymphocytes, and monocyte-to-lymphocyte ratio (MLr) were analyzed in clots extracted after endovascular treatment (EVT) and in peripheral blood. Large arterial atherosclerosis (LAA) strokes and high-risk cardioembolic (HRCE) strokes were matched by demographics and acute reperfusion ...
Source: Translational Stroke Research - October 28, 2022 Category: Neurology Source Type: research

Gut Microbiota in Ischemic Stroke: Role of Gut Bacteria-Derived Metabolites
AbstractIschemic stroke (IS) remains a leading cause of death and long-term disability globally. Several mechanisms including glutamate excitotoxicity, calcium overload, neuroinflammation, oxidative stress, mitochondrial damage, and apoptosis are known to be involved in the pathogenesis of IS, but the underlying pathophysiology mechanisms of IS are not fully clarified. During the past decade, gut microbiota were recognized as a key regulator to affect the health of the host either directly or via their metabolites. Recent studies indicate that gut bacterial dysbiosis is closely related to hypertension, diabetes, obesity, d...
Source: Translational Stroke Research - October 24, 2022 Category: Neurology Source Type: research

Correction to: Clinical Significance and Influencing Factors of Microvascular Tissue Reperfusion After Macrovascular Recanalization
(Source: Translational Stroke Research)
Source: Translational Stroke Research - October 21, 2022 Category: Neurology Source Type: research

A Genome-Wide Association Study of Outcome After Aneurysmal Subarachnoid Haemorrhage: Discovery Analysis
AbstractCandidate gene studies have identified genetic variants associated with clinical outcomes following aneurysmal subarachnoid haemorrhage (aSAH), but no genome-wide association studies have been performed to date. Here we report the results of the discovery phase of a two-stage genome-wide meta-analysis of outcome after aSAH. We identified 157 independent loci harbouring 756 genetic variants associated with outcome after aSAH (p <  1 × 10−4), which require validation. A single variant (rs12949158), inSPNS2, achieved genome-wide significance (p = 4.29 × 10−8) implicating sphingosine-1-phosphat...
Source: Translational Stroke Research - October 20, 2022 Category: Neurology Source Type: research

Associations Between Drug Treatments and the Risk of Aneurysmal Subarachnoid Hemorrhage: a Systematic Review and Meta-analysis
AbstractThere is increasing interest in drug therapy for preventing aneurysmal subarachnoid hemorrhage (aSAH). We aimed to comprehensively evaluate the association between drug use and the risk of aSAH. We searched PubMed and Scopus from the databases ’ inception until December 2021. Observational studies reporting the association between any drug therapy and aSAH were included. The odds ratios (ORs) for each drug used in aSAH were meta-analyzed with a random-effect model. According to the systematic review, 25 observational studies were eligib le for the present study. Four therapeutic purpose-based classes (e.g., lipid...
Source: Translational Stroke Research - October 15, 2022 Category: Neurology Source Type: research

Reinventing the Penumbra — the Emerging Clockwork of a Multi-modal Mechanistic Paradigm
AbstractThe concept of the ischemic penumbra was originally defined as the area around a necrotic stroke core and seen as the tissue at imminent risk of further damage. Today, the penumbra is generally considered as time-sensitive hypoperfused brain tissue with decreased oxygen and glucose availability, salvageable tissue as treated by intervention, and the potential target for neuroprotection in focal stroke. The original concept entailed electrical failure and potassium release but one short of neuronal cell death and was based on experimental stroke models, later confirmed in clinical imaging studies. However, even thou...
Source: Translational Stroke Research - October 11, 2022 Category: Neurology Source Type: research

A New Paradigm for Neuroprotection Clinical Trials for Acute Ischemic Stroke
(Source: Translational Stroke Research)
Source: Translational Stroke Research - October 11, 2022 Category: Neurology Source Type: research

cPKC γ-Modulated Autophagy Contributes to Ischemic Preconditioning–Induced Neuroprotection in Mice with Ischemic Stroke via mTOR-ULK1 Pathway
In this study, adult and postnatal 1-day-old C57BL/6 J wild -type (cPKCγ+/+) and knockout (cPKC γ−/−) mice were used to establish in vivo and in vitro IPC models. The results showed that IPC pretreatment alleviated neuronal damage caused by lethal ischemia, which could be suppressed by autophagy inhibitor 3-MA or bafilomycin A1. Meanwhile, cPKC γ knockout blocked IPC-induced neuroprotection, accompanied by significant increase of LC3-I to LC3-II conversion and Beclin 1 protein level, and a significant decrease in p62 protein level. Immunofluorescent staining results showed a decrease of LC3 puncta numbers in IPC-tr...
Source: Translational Stroke Research - October 10, 2022 Category: Neurology Source Type: research

Elevated Serum Ninjurin-1 Is Associated with a High Risk of Large Artery Atherosclerotic Acute Ischemic Stroke
AbstractNinjurin-1 is a novel adhesion molecule which is involved in many inflammatory diseases. Functional blockage of Ninjurin-1 has exerted an atheroprotective effect. The aim of the study is to explore the association between serum Ninjurin-1 and the risk of large artery atherosclerotic acute ischemic stroke. From August 2020 through December 2021, patients with large artery atherosclerotic acute ischemic stroke (LAA-AIS) admitted to the First Hospital Affiliated to Soochow University, and age- and sex-matched controls free of ischemic stroke were recruited. Serum Ninj1 was measured with an enzyme-linked immunosorbent ...
Source: Translational Stroke Research - October 7, 2022 Category: Neurology Source Type: research

GPR39 Knockout Worsens Microcirculatory Response to Experimental Stroke in a Sex-Dependent Manner
AbstractNo current treatments target microvascular reperfusion after stroke, which can contribute to poor outcomes even after successful clot retrieval. The G protein –coupled receptor GPR39 is expressed in brain peri-capillary pericytes, and has been implicated in microvascular regulation, but its role in stroke is unknown. We tested the hypothesis that GPR39 plays a protective role after stroke, in part due to preservation of microvascular perfusion. We gener ated GPR39 knockout (KO) mice and tested whether GPR39 gene deletion worsens capillary blood flow and exacerbates brain injury and functional deficit after focal ...
Source: Translational Stroke Research - October 1, 2022 Category: Neurology Source Type: research

Dental Pulp Stem Cell-Derived Conditioned Medium Alleviates Subarachnoid Hemorrhage-Induced Microcirculation Impairment by Promoting M2 Microglia Polarization and Reducing Astrocyte Swelling
This study aimed to investigate whether dental pulp stem cell conditioned medium (DPSC-CM) ameliorates SAH-induced microcirculation impairment and the underlying mechanisms. SAH was induced via intrathecal injection of fresh autologous blood in Wistar male adult rat. DPSC-CM or DPSC-CM  + insulin growth factor-1 (IGF-1) antibody was randomly administered by intrathecal route 5 min after SAH induction. To evaluate the underlying mechanisms of DPSC-CM in the treatment of SAH, primary rat astrocyte and microglia co-cultures were challenged with hemolysate or SAH-patient CSF in t he presence or absence of DPSC-CM. The res...
Source: Translational Stroke Research - October 1, 2022 Category: Neurology Source Type: research

Endothelial Cell –Derived Let-7c-Induced TLR7 Activation on Smooth Muscle Cell Mediate Vascular Wall Remodeling in Moyamoya Disease
AbstractMoyamoya disease (MMD) is characterized by frequent migration and phenotypic transformation of vascular smooth muscle cells (VSMCs) in the intima layer of blood vessels. However, the underlying mechanism is unclear. Toll-like receptor (TLR) 7 is abundantly expressed in smooth muscle cells (SMCs) in multiple vascular diseases, which might be linked to the disease-associated vascular remodeling. In the present study, the expression of TLR7 in MMD vessels was examined using the superficial temporal artery (STA) and middle cerebral artery (MCA) from MMD patients. Furthermore, the effect of TLR7 activation on the VSMC p...
Source: Translational Stroke Research - October 1, 2022 Category: Neurology Source Type: research