Subarachnoid hemorrhage-associated brain injury and neurobehavioral deficits are reversed with synthetic adropin treatment through sustained Ser1179 phosphorylation of endothelial nitric oxide synthase.

Background: Subarachnoid hemorrhage (SAH) is a life-threatening vascular condition without satisfactory treatment options. The secreted peptide adropin is highly expressed in the human brain and has neuroprotective effects in brain injury models, including actions involving the cerebrovasculature. Here, we report an endothelial nitric oxide synthase (eNOS)-dependent effect of synthetic adropin treatment that reverses the deleterious effects of SAH.

Neutrophils: Novel Contributors to Estrogen-Dependent Intracranial Aneurysm Rupture Via Neutrophil Extracellular Traps.

Background Intracranial aneurysms (IAs) are more prevalent in women than men, and aneurysmal subarachnoid hemorrhage disproportionately affects postmenopausal women. These sex differences suggest estrogen protects against IA progression that can lead to rupture, but the underlying mechanisms are not fully understood. Although studies have demonstrated estrogen regulates inflammatory processes that contribute to IA pathogenesis, the role of neutrophils remains to be characterized.

Clopidogrel Is Associated with Reduced Likelihood of Aneurysmal Subarachnoid Hemorrhage: a Multi-Center Matched Retrospective Analysis.

Maladaptive inflammation underlies the formation and rupture of human intracranial aneurysms. There is a growing body of evidence that anti-inflammatory pharmaceuticals may beneficially modulate this process. Clopidogrel (Plavix) is a commonly used irreversible P2Y12 receptor antagonist with anti-inflammatory activity.

Theory for High-Throughput Genetic Interaction Screening.

Systematic, genome-scale genetic screens have been instrumental for elucidating genotype-phenotype relationships, but approaches for probing genetic interactions have been limited to at most ∼100 pre-selected gene combinations in mammalian cells. Here, we introduce a theory for high-throughput genetic interaction screens. The theory extends our recently developed Multiplexing using Spectral Imaging and Combinatorics (MuSIC) approach to propose ∼10 spectrally unique, genetically encoded MuSIC barcodes from 18 currently available fluorescent proteins.

Decrease in cortical vein opacification predicts outcome after aneurysmal subarachnoid hemorrhage.

Background: The pathophysiology of brain injury after aneurysmal subarachnoid hemorrhage (aSAH) remains incompletely understood. Cerebral venous flow patterns may be a marker of hemodynamic disruptions after aneurysm rupture. We hypothesized that a decrease in venous filling after aSAH would predict cerebral ischemia and poor outcome.

Investigation and modulation of interleukin-6 following subarachnoid hemorrhage: targeting inflammatory activation for cerebral vasospasm.

Background: Cerebral vasospasm (CV) can contribute to significant morbidity in subarachnoid hemorrhage (SAH) patients. A key unknown is how CV induction is triggered following SAH.

Methods: Human aneurysmal blood and cerebral spinal fluid were collected for evaluation.

Headache persisting after aneurysmal subarachnoid hemorrhage: A narrative review of pathophysiology and therapeutic strategies.

Objective: This narrative review of the literature concerns persistent headache attributed to past non-traumatic subarachnoid hemorrhage (SAH), based off demographic and clinical features, what are pathophysiologic mechanisms by which these headaches occur, which medical and interventional treatments have the most evidence for pain alleviation, and what pre-clinical evidence is there for emerging treatments for these patients.

Background: Following initial stabilization and treatment of spontaneous SAH, most commonly due to aneurysmal rupture, headache in the immediate inpatient setting and persisting after discharge are an important cause of morbidity. These headaches often receive heterogenous treatment of uncertain efficacy, and the risk factors and pathophysiology of their development has received little study.

Mesowestern Blot: Simultaneous Analysis of Hundreds of Submicroliter Lysates.

Western blotting is a widely used technique for molecular-weight-resolved analysis of proteins and their posttranslational modifications, but high-throughput implementations of the standard slab gel arrangement are scarce. The previously developed Microwestern requires a piezoelectric pipetting instrument, which is not available for many labs. Here, we report the Mesowestern blot, which uses a 3D-printable gel casting mold to enable high-throughput Western blotting without piezoelectric pipetting and is compatible with the standard sample preparation and small (∼1 μL) sample sizes.

A scalable, open-source implementation of a large-scale mechanistic model for single cell proliferation and death signaling.

Mechanistic models of how single cells respond to different perturbations can help integrate disparate big data sets or predict response to varied drug combinations. However, the construction and simulation of such models have proved challenging. Here, we developed a python-based model creation and simulation pipeline that converts a few structured text files into an SBML standard and is high-performance- and cloud-computing ready.

Combination release of chemokines from coated coils to target aneurysm healing.

Background: Monocyte chemoattractant protein 1 (MCP-1) and osteopontin (OPN) have been identified separately as key mediators of the aneurysm healing process following coil embolization in the rodent model. The ability of protein coated coils to accelerate this process is currently unknown.

Objective: To create coils coated with both MCP-1 and OPN to target aneurysm healing.

Delayed cerebral ischemia: A look at the role of endothelial dysfunction, emerging endovascular management, and glymphatic clearance.

Delayed cerebral ischemia (DCI) contributes to extensive morbidity and mortality for patients with aneurysmal subarachnoid hemorrhage (SAH). Recent contributions to the basic and translational investigation of DCI have shed light on emerging concepts that may aid in the development of novel therapeutics. A clear association between cerebral vasospasm (CV) and DCI exists, but it is also known that DCI can affect brain parenchyma remote from sites of vasospasm.

Gastrointestinal Microbiome and Neurologic Injury.

Communication between the enteric nervous system (ENS) of the gastrointestinal (GI) tract and the central nervous system (CNS) is vital for maintaining systemic homeostasis. Intrinsic and extrinsic neurological inputs of the gut regulate blood flow, peristalsis, hormone release, and immunological function. The health of the gut microbiome plays a vital role in regulating the overall function and well-being of the individual.

Behavioral Pediatrics: A Team-Based Interprofessional Approach.

An interprofessional approach to pediatric behavioral care is increasingly important in the care of pediatric patients, who present to healthcare settings with a wide variety of concerns ranging from potty training to depression. Previously, much of the care of these patients have focused on a narrow approach to the problem, based on the expertise of the professional providing care. Faculty from three disciplines: Social Work, Psychology, and Medicine collaborated to design a course for students from these three disciplines to collaborate in attaining three goals: (1) reinforce the importance of multidisciplinary collaboration, (2) share clinical techniques and skills in a simulated interprofessional setting, and (3) practice collaboration within interprofessional teams.

Interleukin-6: Important Mediator of Vasospasm Following Subarachnoid Hemorrhage.

The correlation of neuroinflammation with the development of cerebral vasospasm following subarachnoid hemorrhage has been well documented in the literature; both clinical and preclinical. The exact mechanisms by which this process occurs, however, are poorly elucidated. Recent evidence indicates that interleukin-6 is not only an important prognostic biomarker for subarachnoid hemorrhage and subsequent vasospasm development but also an integral component in the progression of injury following initial insult.

A Modification to a Murine Model for Intracranial Aneurysm Formation and Rupture.

Between 3.6% and 6.0% of the population has an intracranial aneurysm.

Pathophysiology of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: A Review.

Delayed cerebral ischemia is a major predictor of poor outcomes in patients who suffer subarachnoid hemorrhage. Treatment options are limited and often ineffective despite many years of investigation and clinical trials. Modern advances in basic science have produced a much more complex, multifactorial framework in which delayed cerebral ischemia is better understood and novel treatments can be developed.

NLRP3 inhibition attenuates early brain injury and delayed cerebral vasospasm after subarachnoid hemorrhage.

Background: The NLRP3 inflammasome is a critical mediator of several vascular diseases through positive regulation of proinflammatory pathways. In this study, we defined the role of NLRP3 in both the acute and delayed phases following subarachnoid hemorrhage (SAH). SAH is associated with devastating early brain injury (EBI) in the acute phase, and those that survive remain at risk for developing delayed cerebral ischemia (DCI) due to cerebral vasospasm.

Aneurysmal Subarachnoid Hemorrhage in Patients with Coronavirus Disease 2019 (COVID-19): A Case Series.

Objective: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is a pressing public health issue. Although most cases do not result in severe illness requiring hospitalization, there is increasing evidence that SARS-CoV-2-induced inflammation can exacerbate pre-existing diseases. We sought to describe the characteristics of patients with aneurysmal subarachnoid hemorrhage who were actively or very recently infected with SARS-CoV-2.

Inflammatory myofibroblastic tumor masquerading as an anterior choroidal artery fusiform aneurysm.

Background: Inflammatory myofibroblastic tumor is a rare, poorly understood tumor that has been found to occur in almost every organ tissue. Its location within the central nervous system is uncommon, and patients tend to present with nonspecific symptoms.

Case Description: A female in her eighth decade presented to neurosurgery clinic with complaints of headache and dizziness.

Early chemoprophylaxis for deep venous thrombosis does not increase the risk of hematoma expansion in patients presenting with spontaneous intracerebral hemorrhage.

Background: Spontaneous intracerebral hemorrhage (ICH) is a significant cause of morbidity and mortality worldwide. The development of venous thromboembolism (VTE), including deep venous thrombosis or pulmonary embolism, is correlated with negative outcomes following ICH. Due to the risk of hematoma expansion associated with the use of VTE chemoprophylaxis, there remains significant debate about the optimal timing for its initiation following ICH.

Ticagrelor resistance: a case series and algorithm for management of non-responders.

The placement of cervical and intracranial stents requires the administration of antiplatelet drugs to prevent thromboembolic complications. Ticagrelor has emerged as the most widely used alternative in clopidogrel non-responders owing to its potent antiplatelet effects. Because ticagrelor does not require hepatic activation, many neurointerventionalists choose to forgo laboratory testing of platelet inhibition.