Aging-associated deficit in CCR7 is linked to worsened glymphatic function, cognition, neuroinflammation, and β-amyloid pathology

Aging leads to a progressive deterioration of meningeal lymphatics and peripheral immunity, which may accelerate cognitive decline. We hypothesized that an age-related reduction in C-C chemokine receptor type 7 (CCR7)-dependent egress of immune cells through the lymphatic vasculature mediates some aspects of brain aging and potentially exacerbates cognitive decline and Alzheimer\u27s disease-like brain β-amyloid (Aβ) pathology. We report a reduction in CCR7 expression by meningeal T cells in old mice that is linked to increased effector and regulatory T cells. Hematopoietic CCR7 deficiency mimicked the aging-associated changes in meningeal T cells and led to reduced glymphatic influx and cognitive impairment. Deletion of CCR7 in 5xFAD transgenic mice resulted in deleterious neurovascular and microglial activation, along with increased Aβ deposition in the brain. Treating old mice with anti-CD25 antibodies alleviated the exacerbated meningeal regulatory T cell response and improved cognitive function, highlighting the therapeutic potential of modulating meningeal immunity to fine-tune brain function in aging and in neurodegenerative diseases

A topical review of the feasibility and reliability of ambulance-based telestroke

BackgroundAmbulance-based telemedicine is an innovative strategy through which transport time can be used to rapidly and accurately triage stroke patients (i.e., mobile telestroke). The acute phase of stroke is a time-sensitive emergency, and delays in care during this phase worsen outcomes. In this literature review, we analyzed studies that investigated the feasibility and reliability of ambulance based telestroke.MethodsWe followed PRISMA guidelines to perform a keyword-based search of PubMed, Web of Science, CINHAL, and Academic Search Complete databases. We reviewed references of search-identified articles to screen for additional articles. Articles for inclusion were selected according to author consensus in consideration of the studies' investigation of feasibility, reliability, or validity of ambulance-based telestroke.ResultsWe identified 67 articles for secondary screening from which 19 articles were selected for full text review. The selected studies reported diverse methods of development, implementation, and assessment of ambulance-based telestroke systems. Although the methods and results varied among these studies, most concluded that the implementation of ambulance based telestroke is feasible.ConclusionThis topical review suggests that ambulance based telestroke is a feasible method for enhanced prehospital stroke care in a variety of settings. Further prospective research is needed to assess the real-world challenges and to identify additional strategies that bolster rapid and accurate prehospital assessment of acute stroke patients

Meningeal lymphatics affect microglia responses and anti-Aβ immunotherapy

Alzheimer's disease (AD) is the most prevalent cause of dementia1. Although there is no effective treatment for AD, passive immunotherapy with monoclonal antibodies against amyloid beta (Aβ) is a promising therapeutic strategy2,3. Meningeal lymphatic drainage has an important role in the accumulation of Aβ in the brain4, but it is not known whether modulation of meningeal lymphatic function can influence the outcome of immunotherapy in AD. Here we show that ablation of meningeal lymphatic vessels in 5xFAD mice (a mouse model of amyloid deposition that expresses five mutations found in familial AD) worsened the outcome of mice treated with anti-Aβ passive immunotherapy by exacerbating the deposition of Aβ, microgliosis, neurovascular dysfunction, and behavioural deficits. By contrast, therapeutic delivery of vascular endothelial growth factor C improved clearance of Aβ by monoclonal antibodies. Notably, there was a substantial overlap between the gene signature of microglia from 5xFAD mice with impaired meningeal lymphatic function and the transcriptional profile of activated microglia from the brains of individuals with AD. Overall, our data demonstrate that impaired meningeal lymphatic drainage exacerbates the microglial inflammatory response in AD and that enhancement of meningeal lymphatic function combined with immunotherapies could lead to better clinical outcomes

Mechanical thrombectomy for the treatment of primary and secondary anterior cerebral artery occlusions: insights from STAR

BACKGROUNDThe safety and efficacy of mechanical thrombectomy (MT) for the treatment of acute anterior cerebral artery (ACA) occlusions have not clearly been delineated. Outcomes may be impacted based on whether the occlusion is isolated to the ACA (primary ACA occlusion) or occurs in conjunction with other cerebral arteries (secondary).METHODSWe performed a retrospective review of the multicenter Stroke Thrombectomy and Aneurysm (STAR) database. All patients with MT-treated primary or secondary ACA occlusions were included. Baseline characteristics, procedural outcomes, complications, and clinical outcomes were collected. Primary and secondary ACA occlusions were compared using the Mann-Whitney U test and Kruskal-Willis test for continuous variables and the χ2 test for categorical variables.RESULTSThe study cohort comprised 238 patients with ACA occlusions (49.2% female, median (SD) age 65.6 (16.7) years). The overall rate of successful recanalization was 75%, 90-day good functional outcome was 23%, and 90-day mortality was 35%. There were 44 patients with a primary ACA occlusion and 194 patients with a secondary ACA occlusion. When adjusted for baseline variables, the rates of successful recanalization (68% vs 76%, P=0.27), 90-day good functional outcome (41% vs 19%, P=0.38), and mortality at 90 days (25% vs 38%, P=0.12) did not differ between primary and secondary ACA occlusion groups.CONCLUSIONClinical and procedural outcomes are similar between MT-treated primary and secondary ACA occlusions for select patients. Our findings demonstrate the need for established criteria to determine ideal patient and ACA stroke characteristics amenable to MT treatment