Vascular Neurology Considerations for Antiamyloid Immunotherapy: A Science Advisory From the American Heart Association.

Antibodies directed at the amyloid-β peptide offer the prospect of disease-modifying therapy for early-stage Alzheimer disease but also carry the risk of brain edema or bleeding events, collectively designated amyloid-related imaging abnormalities. Introduction of the antiamyloid immunotherapies into practice is therefore likely to present a new set of questions for clinicians treating patients with cerebrovascular disease: Which manifestations of cerebrovascular disease should preclude, or permit, antibody treatment? Is it safe to prescribe amyloid immunotherapies to individuals who require antithrombotic treatment, or to administer thrombolysis to antibody-treated individuals with acute stroke? How should severe amyloid-related imaging abnormalities be managed? This science advisory summarizes the data and key considerations to guide these challenging decisions as the medical community collects further data and experience with these groundbreaking agents.

New Directions in Infection-Associated Ischemic Stroke.

The relationship between infections and stroke has not been fully characterized, probably delaying the development of specific treatments. This narrative review addresses mechanisms of stroke linked to infections, including hypercoagulability, endothelial dysfunction, vasculitis, and impaired thrombolysis. SARS-CoV-2, the virus that causes COVID-19, may promote the development of stroke, which may represent its most severe neurological complication.

Erythrocyte-brain endothelial interactions induce microglial responses and cerebral microhemorrhages in vivo.

Background: Cerebral microhemorrhages (CMH) are associated with stroke, cognitive decline, and normal aging. Our previous study shows that the interaction between oxidatively stressed red blood cells (RBC) and cerebral endothelium may underlie CMH development. However, the real-time examination of altered RBC-brain endothelial interactions in vivo, and their relationship with clearance of stalled RBC, microglial responses, and CMH development, has not been reported.

Changes in beat-to-beat blood pressure and pulse rate variability following stroke.

Associations between cerebrovascular disease and impaired autonomic function and cerebrovascular reactivity have led to increased interest in variability of heart rate (HRV) and blood pressure (BPV) following stroke. In this study, beat-to-beat pulse rate variability (PRV) and BPV were measured in clinically stable stroke patients (6 ischemic, 2 hemorrhagic) at least one year after their last cerebrovascular event. Beat-to-beat blood pressure (BP) measurements were collected from subjects while resting in the sitting position for one hour.

The 2022 FASEB Virtual Catalyst Conference on the Cardiac Interatrial Septum and Stroke Risk, December 7, 2022.

There is emerging evidence that the cardiac interatrial septum has an important role as a thromboembolic source for ischemic strokes. There is little consensus on treatment of patients with different cardiac interatrial morphologies or pathologies who have had stroke. In this paper, we summarize the important background, diagnostic, and treatment considerations for this patient population as presented during the Federation of American Societies for Experimental Biology (FASEB) Virtual Catalytic Conference on the Cardiac Interatrial Septum and Stroke Risk, held on December 7, 2022.

Comparative studies between the murine immortalized brain endothelial cell line (bEnd.3) and induced pluripotent stem cell-derived human brain endothelial cells for paracellular transport.

Brain microvascular endothelial cells, forming the anatomical site of the blood-brain barrier (BBB), are widely used as in vitro complements to in vivo BBB studies. Among the immortalized cells used as in vitro BBB models, the murine-derived bEnd.3 cells offer culturing consistency and low cost and are well characterized for functional and transport assays, but result in low transendothelial electrical resistance (TEER).

Insights Into the Mechanisms of Brain Endothelial Erythrophagocytosis.

The endothelial cells which form the inner cellular lining of the vasculature can act as non-professional phagocytes to ingest and remove emboli and aged/injured red blood cells (RBCs) from circulation. We previously demonstrated an erythrophagocytic phenotype of the brain endothelium for oxidatively stressed RBCs with subsequent migration of iron-rich RBCs and RBC degradation products across the brain endothelium , in the absence of brain endothelium disruption. However, the mechanisms contributing to brain endothelial erythrophagocytosis are not well defined, and herein we elucidate the cellular mechanisms underlying brain endothelial erythrophagocytosis.

Capacity Building for a New Multicenter Network Within the ECHO IDeA States Pediatric Clinical Trials Network.

Research capacity building is a critical component of professional development for pediatrician scientists, yet this process has been elusive in the literature. The ECHO IDeA States Pediatric Clinical Trials Network (ISPCTN) seeks to implement pediatric trials across medically underserved and rural populations. A key component of achieving this objective is building pediatric research capacity, including enhancement of infrastructure and faculty development.

Simple methodology to visualize whole-brain microvasculature in three dimensions.

To explore brain architecture and pathology, a consistent and reliable methodology to visualize the three-dimensional cerebral microvasculature is beneficial. Perfusion-based vascular labeling is quick and easily deliverable. However, the quality of vascular labeling can vary with perfusion-based labels due to aggregate formation, leakage, rapid photobleaching, and incomplete perfusion.

Cerebral Blood Flow in Chronic Kidney Disease.

The prevalence of mild cognitive impairment increases with age and is further exacerbated by chronic kidney disease (CKD). CKD is associated with (1) mild cognitive impairment, (2) impaired endothelial function, (3) impaired blood-brain barrier, (4) increased cerebral microhemorrhage burden, (5) increased cerebral blood flow (CBF), (6) impaired cerebral autoregulation, (7) impaired cerebrovascular reactivity, and (8) increased arterial stiffness. We report preliminary findings from our group that demonstrate altered cerebrovascular reactivity in a mouse model of CKD-associated vascular calcification.

Point-of-care p24 antigen detection for early infant diagnosis of HIV infection: cross-sectional and longitudinal studies in Zambia.

Background: Early infant diagnosis of HIV infection is challenging in sub-Saharan Africa, particularly in rural areas, leading to delays in diagnosis and treatment. Use of a point-of-care test would overcome many challenges. This study evaluated the validity of a novel point-of-care p24 antigen detection test (LYNX) in rural and urban settings in southern Zambia.

Mechanisms of Cerebral Microbleeds.

Cerebral microbleeds (CMB) are a common MRI finding, representing underlying cerebral microhemorrhages (CMH). The etiology of CMB and microhemorrhages is obscure. We conducted a pathological investigation of CMH, combining standard and immunohistological analyses of postmortem human brains.

The Medial Pontine Mid-Tegmentum Syndrome.

Isolated pontine infarcts are common and are often associated with well-described syndromes that are classified based on their specific clinical presentation and arterial stroke territories. Here we present a case of acute combined diplopia and unilateral lower extremity sensory abnormality. Diffusion-weighted magnetic resonance imaging revealed a punctate area of acute ischemia in the right medial pontine mid-tegmentum.

Bihemisphere Ischemia Due to a Unilateral Lesion: A Case Report.

Bihemispheric ischemic strokes secondary to unilateral vessel disease are uncommon. We present the case of a 70-year-old man with multiple acute/subacute bilateral infarcts. The patient was found to have stenosis of the left internal carotid artery secondary to herpes zoster ophthalmicus vasculopathy, with involvement of the left proximal middle and anterior cerebral arteries.

Bilateral Limb-Shaking Transient Ischemic Attacks.

Limb shaking is a rare manifestation of transient ischemic attacks (TIA) associated with carotid occlusion, mostly unilateral events. We describe the case of a 69 year-old man who presented with repeated episodes of irregular jerking movements in the bilateral upper and lower extremities, precipitated by standing up. Cerebral angiograms revealed occlusion of both internal carotid arteries, and the patient's symptoms responded to targeted blood pressure management.

Effects of Dabigatran in Mouse Models of Aging and Cerebral Amyloid Angiopathy.

Oral anticoagulants are a critical component of stroke prevention, but carry a risk of brain hemorrhage. These hemorrhagic complications tend to occur in elderly individuals, especially those with predisposing conditions such as cerebral amyloid angiopathy (CAA). Clinical evidence suggests that non-vitamin K antagonist oral anticoagulants are safer than traditional oral anticoagulants.

Blood Pressure Circadian Variation, Cognition and Brain Imaging in 90+ Year-Olds.

: To analyze the relationship between blood pressure (BP) variables, including circadian pattern, and cognition in 90+ year-olds. : Twenty-four hour ambulatory BP monitoring was completed on 121 participants drawn from a longitudinal study of aging and dementia in the oldest-old. Various measures of BP and its variability, including nocturnal dipping, were calculated.

The feasibility of fingerstick blood collection for point-of-care HIV-1 viral load monitoring in rural Zambia.

Viral load monitoring for HIV treatment is recommended but not feasible in many settings. A point-of-care test using capillary blood would increase access but may require up to 200 μL of blood to achieve a lower limit of detection of 1000 copies/mL. This cross-sectional study evaluated the feasibility of collecting 200 μL of capillary blood and blood collection preferences among adults in rural Zambia.

Brain Endothelial Erythrophagocytosis and Hemoglobin Transmigration Across Brain Endothelium: Implications for Pathogenesis of Cerebral Microbleeds.

Peripheral endothelial cells are capable of erythrophagocytosis, but data on brain endothelial erythrophagocytosis are limited. We studied the relationship between brain endothelial erythrophagocytosis and cerebral microhemorrhage, the pathological substrate of MRI-demonstrable cerebral microbleeds. To demonstrate the erythrophagocytic capability of the brain endothelium, we studied the interactions between brain endothelial cells and red blood cells exposed to oxidative stress , and developed a new cerebral microbleeds model to study the subsequent passage of hemoglobin across the brain endothelial monolayer.

Aging exacerbates development of cerebral microbleeds in a mouse model.

Background: Cerebral microhemorrhages (CMH) are commonly found in the aging brain. CMH are also the neuropathological substrate of cerebral microbleeds (CMB), demonstrated on brain MRI. Recent studies demonstrate the importance of systemic inflammation in CMH development, but the relationships among inflammation, aging, and CMH development are not well-defined.

Immiscible phase filter extraction and equivalent amplification of genotypes 1-6 of hepatitis C RNA: The building blocks for point-of-care diagnosis.

The lack of hepatitis C virus (HCV) diagnostic tests designed for use in decentralized settings is a major obstacle for providing access to treatment and prevention services particularly in low and middle income countries. Here we describe the development and validation of two building blocks of the HCV Quant Assay, a test in development for point-of-care use: 1) an RT-qPCR assay with noncompetitive internal control that equivalently detects the 6 major HCV genotypes and 2) an automated sample prep method using immiscible phase filter technology. This novel assay has wide dynamic range of HCV quantification and a limit of detection of 30IU/ml with 200μl specimen volume.

Effects of phosphodiesterase 3A modulation on murine cerebral microhemorrhages.

Background: Cerebral microbleeds (CMB) are MRI-demonstrable cerebral microhemorrhages (CMH) which commonly coexist with ischemic stroke. This creates a challenging therapeutic milieu, and a strategy that simultaneously protects the vessel wall and provides anti-thrombotic activity is an attractive potential approach. Phosphodiesterase 3A (PDE3A) inhibition is known to provide cerebral vessel wall protection combined with anti-thrombotic effects.