A feature of maternal sleep apnea during gestation causes autism-relevant neuronal and behavioral phenotypes in offspring.

Mounting epidemiologic and scientific evidence indicates that many psychiatric disorders originate from a complex interplay between genetics and early life experiences, particularly in the womb. Despite decades of research, our understanding of the precise prenatal and perinatal experiences that increase susceptibility to neurodevelopmental disorders remains incomplete. Sleep apnea (SA) is increasingly common during pregnancy and is characterized by recurrent partial or complete cessations in breathing during sleep. SA causes pathological drops in blood oxygen levels (intermittent hypoxia, IH), often hundreds of times each night. Although SA is known to cause adverse pregnancy and neonatal outcomes, the long-term consequences of maternal SA during pregnancy on brain-based behavioral outcomes and associated neuronal functioning in the offspring remain unknown. We developed a rat model of maternal SA during pregnancy by exposing dams to IH, a hallmark feature of SA, during gestational days 10 to 21 and investigated the consequences on the offspring's forebrain synaptic structure, synaptic function, and behavioral phenotypes across multiples stages of development. Our findings represent a rare example of prenatal factors causing sexually dimorphic behavioral phenotypes associated with excessive (rather than reduced) synapse numbers and implicate hyperactivity of the mammalian target of rapamycin (mTOR) pathway in contributing to the behavioral aberrations. These findings have implications for neuropsychiatric disorders typified by superfluous synapse maintenance that are believed to result, at least in part, from largely unknown insults to the maternal environment

Pragmatic solutions to reduce the global burden of stroke: a World Stroke Organization–Lancet Neurology Commission

Stroke is the second leading cause of death worldwide. The burden of disability after a stroke is also large, and is increasing at a faster pace in low-income and middle-income countries than in high-income countries. Alarmingly, the incidence of stroke is increasing in young and middle-aged people (ie, age <55 years) globally. Should these trends continue, Sustainable Development Goal 3.4 (reducing the burden of stroke as part of the general target to reduce the burden of non-communicable diseases by a third by 2030) will not be met. In this Commission, we forecast the burden of stroke from 2020 to 2050. We project that stroke mortality will increase by 50%—from 6·6 million (95% uncertainty interval [UI] 6·0 million–7·1 million) in 2020, to 9·7 million (8·0 million–11·6 million) in 2050—with disability-adjusted life-years (DALYs) growing over the same period from 144·8 million (133·9 million–156·9 million) in 2020, to 189·3 million (161·8 million–224·9 million) in 2050. These projections prompted us to do a situational analysis across the four pillars of the stroke quadrangle: surveillance, prevention, acute care, and rehabilitation. We have also identified the barriers to, and facilitators for, the achievement of these four pillars. Disability-adjusted life-years (DALYs) The sum of the years of life lost as a result of premature mortality from a disease and the years lived with a disability associated with prevalent cases of the disease in a population. One DALY represents the loss of the equivalent of one year of full health On the basis of our assessment, we have identified and prioritised several recommendations. For each of the four pillars (surveillance, prevention, acute care, and rehabilitation), we propose pragmatic solutions for the implementation of evidence-based interventions to reduce the global burden of stroke. The estimated direct (ie, treatment and rehabilitation) and indirect (considering productivity loss) costs of stroke globally are in excess of US$891 billion annually. The pragmatic solutions we put forwards for urgent implementation should help to mitigate these losses, reduce the global burden of stroke, and contribute to achievement of Sustainable Development Goal 3.4, the WHO Intersectoral Global Action Plan on epilepsy and other neurological disorders (2022–2031), and the WHO Global Action Plan for prevention and control of non-communicable diseases. Reduction of the global burden of stroke, particularly in low-income and middle-income countries, by implementing primary and secondary stroke prevention strategies and evidence-based acute care and rehabilitation services is urgently required. Measures to facilitate this goal include: the establishment of a framework to monitor and assess the burden of stroke (and its risk factors) and stroke services at a national level; the implementation of integrated population-level and individual-level prevention strategies for people at any increased risk of cerebrovascular disease, with emphasis on early detection and control of hypertension; planning and delivery of acute stroke care services, including the establishment of stroke units with access to reperfusion therapies for ischaemic stroke and workforce training and capacity building (and monitoring of quality indicators for these services nationally, regionally, and globally); the promotion of interdisciplinary stroke care services, training for caregivers, and capacity building for community health workers and other health-care providers working in stroke rehabilitation; and the creation of a stroke advocacy and implementation ecosystem that includes all relevant communities, organisations, and stakeholders