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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

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

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

Cannabidiol ’s Multifactorial Mechanisms Has Therapeutic Potential for Aneurysmal Subarachnoid Hemorrhage: a Review
AbstractSubarachnoid hemorrhage (SAH) is a major health burden that accounts for approximately 5% of all strokes. The most common cause of a non-traumatic SAH is the rupture of a cerebral aneurysm. The most common symptom associated with SAH is a headache, often described as “the worst headache of my life.” Delayed cerebral ischemia (DCI) is a major factor associated with patient mortality following SAH and is often associated with SAH-induced cerebral vasospasm (CV). Cannabidiol (CBD) is emerging as a potential drug for many therapeutic purposes, including epilepsy , anxiety, and pain relief. We aim to review the pote...
Source: Translational Stroke Research - September 15, 2022 Category: Neurology Source Type: research

Cerebral Aneurysm and Interleukin-6: a Key Player in Aneurysm Generation and Rupture or Just One of the Multiple Factors?
AbstractIntracranial aneurysm (IA) rupture is a common cause of subarachnoid hemorrhage (SAH) with high mortality and morbidity. Inflammatory interleukins (IL), such as IL-6, play an important role in the occurrence and rupture of IA causing SAH. With this review we aim to elucidate the specific role of IL-6 in aneurysm formation and rupture in preclinical and clinical studies. IL-6 is a novel cytokine in that it has pro-inflammatory and anti-inflammatory signaling pathways. In preclinical and clinical studies of IA formation, elevated and reduced levels of IL-6 are reported. Poor post-rupture prognosis and increased ruptu...
Source: Translational Stroke Research - August 31, 2022 Category: Neurology Source Type: research

The Role of Neutrophil Extracellular Traps in Early Microthrombosis and Brain Injury After Subarachnoid Hemorrhage in Mice
In conclusion, NETs are associated with early microthrombosis after SAH; they may be a novel therapeutic target for early brain injury (EBI) after SAH.
Source: Translational Stroke Research - August 13, 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

A Nationwide Analysis of Aneurysmal Subarachnoid Hemorrhage Mortality, Complications, and Health Economics in the USA
In conclusion, patients with aSAH have high post-operative complication ra tes and costs. Development of novel interventions to reduce complications and improve outcomes is crucial.
Source: Translational Stroke Research - July 26, 2022 Category: Neurology Source Type: research

Metformin Alleviates Delayed Hydrocephalus after Intraventricular Hemorrhage by Inhibiting Inflammation and Fibrosis
In conclusion, metformin attenuated neuroinflammation and subsequent fibrosis after IVH by regulating AMPK /SIRT1/ NF-κB pathways, thereby reducing delayed hydrocephalus. Metformin may be a promising therapeutic agent to prevent delayed hydrocephalus following IVH.
Source: Translational Stroke Research - July 19, 2022 Category: Neurology Source Type: research

Sustained ICP Elevation Is a Driver of Spatial Memory Deficits After Intraventricular Hemorrhage and Leads to Activation of Distinct Microglial Signaling Pathways
In this study, we show that intraventricular hemorrhage only leads to a significant spatial memory deficit in the Morris water maze if it occurs in the setting of an elevated intracranial pressure (ICP). Histopathological analysis of these IVH  + ICP animals did not show evidence of neuronal degeneration in the hippocampal formation after 2 weeks but instead showed significant microglial activation measured by lacunarity and fractal dimensions. RNA sequencing of the hippocampus showed distinct enrichment of genes in the IVH + ICP group but not in IVH alone having activated microglial signaling pathways. The most s...
Source: Translational Stroke Research - July 12, 2022 Category: Neurology Source Type: research

NLRP3 Inflammasome Overactivation in Patients with Aneurysmal Subarachnoid Hemorrhage
AbstractAneurysmal subarachnoid hemorrhage (aSAH) is an uncommon and severe subtype of stroke leading to the loss of many years of productive life. We analyzed NLRP3 activity as well as key components of the inflammasome cascade in monocytes and plasma from 28 patients with aSAH and 14 normal controls using flow cytometry, western blot, ELISA, and qPCR technologies. Our data reveal that monocytes from patients with aSAH present an overactivation of the NLRP3 inflammasome, which results in the presence of high plasma levels of interleukin (IL)-1 β, IL-18, gasdermin D, and tissue factor. Although further research is needed,...
Source: Translational Stroke Research - July 11, 2022 Category: Neurology Source Type: research

Neutrophil Extracellular Traps (NETs): A New Therapeutic Target for Neuroinflammation and Microthrombosis After Subarachnoid Hemorrhage?
AbstractNeutrophil extracellular traps (NETs) play a major role in intrinsic immunity by limiting and killing pathogens. Recently, a series of studies have confirmed that NETs are closely associated with vascular injury and microthrombosis. Furthermore, NETs play an important role in neuroinflammation after ischemic and hemorrhagic stroke. Neuroinflammation and microthrombosis after subarachnoid hemorrhage are key pathophysiological processes associated with poor prognosis, but their crucial formation mechanisms and interventions remain to be elucidated. Could NETs, as an emerging and important pathogenesis, be a new thera...
Source: Translational Stroke Research - June 11, 2022 Category: Neurology Source Type: research

A 90-Day Prognostic Model Based on the Early Brain Injury Indicators after Aneurysmal Subarachnoid Hemorrhage: the TAPS Score
This study aimed to establish a new scoring model based on the early brain injury (EBI) indicators to predict the 90-day functional outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). We retrospectively enrolled 825 patients and prospectively enrolled 108 patients with aSAH who underwent surgical clipping or endovascular coiling (derivation cohort  = 640; validation cohort = 185; prospective cohort = 108) in our institute. We established a logistic regression model based on independent risk factors associated with 90-day unfavorable outcomes. The discrimination of the prognostic model was asses...
Source: Translational Stroke Research - May 14, 2022 Category: Neurology Source Type: research

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