Type-1-to-type-2 transition of brain microvascular pericytes induced by cytokines and disease-associated proteins: Role in neuroinflammation and blood-brain barrier disruption.

While the concept of pericyte heterogeneity in the brain microvasculature is becoming more widely accepted, little is known about how they arise, or their functional contributions to the blood-brain barrier (BBB). We therefore set out to examine the distribution of subtypes of pericytes at the BBB and sought to elucidate some of their functional characteristics by examining their unique mRNA expression patterns. We demonstrate that type-1 pericytes (PC1) that are associated with young healthy brains and BBB homeostasis, can transition into type-2 pericytes (PC2) that are associated with disease and BBB breakdown, both in vitro and in vivo, in the presence of both endogenous and disease associated ligands.

Alterations in Blood-Brain Barrier Integrity and Lateral Ventricle Differ in Rats Exposed to Space Radiation and Social Isolation.

The proposed Mars missions will expose astronauts to long durations of social isolation (SI) and space radiation (SR). These stressors have been shown to alter the brain's macrostructure and microenvironment, including the blood-brain barrier (BBB). Breakdown of the BBB is linked to impaired executive functions and physical deficits, including sensorimotor and neurocognitive impairments.

Evidence for a role of the basolateral amygdala in regulating regional metabolism in the stressed brain.

The brain regulates every physiological process in the body, including metabolism. Studies investigating brain metabolism have shown that stress can alter major metabolic processes, and that these processes can vary between regions. However, no study has investigated how metabolic pathways may be altered by stressor perception, or whether stress-responsive brain regions can also regulate metabolism.

Effects of social isolation and galactic cosmic radiation on fine motor skills and behavioral performance.

Future NASA missions will require astronauts to travel farther and spend longer durations in space than ever before. This will also expose astronauts to longer periods of several physical and psychological challenges, including exposure to space radiation (SR) and periods of social isolation (SI), which could have unknown negative effects on physical and mental health. Each also has the potential to negatively impact sleep which can reduce the ability to cope with stressful experiences and lead to sensorimotor, neurocognitive, and physical deficits.

Femoral Fixation Strength as a Function of Bone Plug Length in Anterior Cruciate Ligament Reconstruction Utilizing Interference Screws.

Purpose:  To determine femoral construct fixation strength as bone plug length decreases in anterior cruciate ligament reconstruction (ACLR).

Methods:  Sixty fresh-frozen bone-patellar tendon-bone allografts were utilized and divided into 20-, 15-, and 10-mm length bone plug groups, subdivided further so that half utilized the patella side (P) for testing and half used the tibial side (T). Ten mm diameter recipient tunnels were created within the anatomic anterior cruciate ligament footprint of 60 cadaveric femurs.

Controllable Stress Increases Rapid Eye Movement Sleep in Rats: Regulation by the Central Nucleus of the Amygdala.

Background: Training with inescapable shock (IS; uncontrollable stressor) is followed by significant decreases in rapid eye movement sleep (REM). However, controllability is important in the effects of stress. We examined the effects of escapable shock (ES; controllable stressor) on sleep and whether the central nucleus of the amygdala (CNA) plays a role in regulating these effects.

Stressor control and regional inflammatory responses in the brain: regulation by the basolateral amygdala.

Increasing evidence has connected the development of certain neuropsychiatric disorders, as well as neurodegenerative diseases, to stress-induced dysregulation of the immune system. We have shown that escapable (ES) and inescapable (IS) footshock stress, and memories associated with ES or IS, can differentially alter inflammatory-related gene expression in brain in a region dependent manner. We have also demonstrated that the basolateral amygdala (BLA) regulates stress- and fear memory-induced alterations in sleep, and that differential sleep and immune responses in the brain to ES and IS appear to be integrated during fear conditioning and then reproduced by fear memory recall.

Sleep and Core Body Temperature Alterations Induced by Space Radiation in Rats.

Sleep problems in astronauts can arise from mission demands and stress and can impact both their health and ability to accomplish mission objectives. In addition to mission-related physical and psychological stressors, the long durations of the proposed Mars missions will expose astronauts to space radiation (SR), which has a significant impact on the brain and may also alter sleep and physiological functions. Therefore, in this study, we assessed sleep, EEG spectra, activity, and core body temperature (CBT) in rats exposed to SR and compared them to age-matched nonirradiated rats.

Differential Impact of Social Isolation and Space Radiation on Behavior and Motor Learning in Rats.

Future missions to Mars will expose astronauts to several physical and psychological challenges, including exposure to space radiation (SR) and periods of social isolation (SI). Each of these stressors, in addition to mission demands, can affect physical and mental health and potentially negatively impact sleep. The effects of inflight stressors may vary with duration and time course, may be additive or compounding, and may vary with individual differences in stress resilience and vulnerability.

Modeling integrated stress, sleep, fear and neuroimmune responses: Relevance for understanding trauma and stress-related disorders.

Sleep and stress have complex interactions that are implicated in both physical diseases and psychiatric disorders. These interactions can be modulated by learning and memory, and involve additional interactions with the neuroimmune system. In this paper, we propose that stressful challenges induce integrated responses across multiple systems that can vary depending on situational variables in which the initial stress was experienced, and with the ability of the individual to cope with stress- and fear-inducing challenges.

Sleep-Disturbance-Induced Microglial Activation Involves CRH-Mediated Galectin 3 and Autophagy Dysregulation.

Chronic sleep disturbances (CSDs) including insomnia, insufficient sleep time, and poor sleep quality are major public health concerns around the world, especially in developed countries. CSDs are major health risk factors linked to multiple neurodegenerative and neuropsychological diseases. It has been suggested that CSDs could activate microglia (Mg) leading to increased neuroinflammation levels, which ultimately lead to neuronal dysfunction.

Controllable and Uncontrollable Stress Differentially Impact Fear Conditioned Alterations in Sleep and Neuroimmune Signaling in Mice.

Stress induces neuroinflammation and disrupts sleep, which together can promote a number of stress-related disorders. Fear memories associated with stress can resurface and reproduce symptoms. Our previous studies have demonstrated sleep outcomes can be modified by stressor controllability following stress and fear memory recall.

Sleep Disturbance Alters Cocaine-Induced Locomotor Activity: Involvement of Striatal Neuroimmune and Dopamine Signaling.

Sleep disorders have high comorbidity with drug addiction and function as major risk factors for developing drug addiction. Recent studies have indicated that both sleep disturbance (SD) and abused drugs could activate microglia, and that increased neuroinflammation plays a critical role in the pathogenesis of both diseases. Whether microglia are involved in the contribution of chronic SDs to drug addiction has never been explored.

Increased medical student understanding of dementia through virtual embodiment.

Given the growing prevalence of Alzheimer's disease (AD), we assessed the impact of virtually embodying someone with progressive AD. This pilot explored students' understanding of individuals' needs with dementia, as well as, the efficacy of virtual reality (VR) as a curricular tool. Second-year medical students (n = 150) completed a pre-survey, Embodied Labs, Inc.

Regulation of dark period sleep by the Amygdala: A microinjection and optogenetics study.

The central nucleus of the amygdala (CNA) projects to brainstem regions that generate and regulate rapid eye movement sleep (REM). We used optogenetics to assess the influence of CNA inputs into reticularis pontis oralis (RPO), pedunculopontine tegmentum (PPT) and nucleus subcoeruleus (SubC) on dark period sleep. We compared these results to effects of microinjections into CNA of the GABA agonist, muscimol (MUS, inhibition of cell bodies) and tetrodotoxin (TTX, inhibition of cell bodies and fibers of passage).

The Basolateral Amygdala Mediates the Role of Rapid Eye Movement Sleep in Integrating Fear Memory Responses.

The basolateral amygdala (BLA) mediates the effects of stress and fear on rapid eye movement sleep (REM) and on REM-related theta (θ) oscillatory activity in the electroencephalograph (EEG), which is implicated in fear memory consolidation. We used optogenetics to assess the potential role of BLA glutamate neurons (BLA) in regulating behavioral, stress and sleep indices of fear memory, and their relationship to altered θ. An excitatory optogenetic construct targeting glutamatergic cells (AAV-CaMKIIα-hChR2-eYFP) was injected into the BLA of mice.

Differential Effect of Light and Dark Period Sleep Fragmentation on Composition of Gut Microbiome and Inflammation in Mice.

Bi-directional interactions amongst the gut microbiota, immune system, and brain function are thought to be critical mediators of health and disease. The role sleep plays in mediating these interactions is not known. We assessed the effects of sleep fragmentation (SF) on the microbiota-gut-brain axis.

Short-Term Sleep Fragmentation Dysregulates Autophagy in a Brain Region-Specific Manner.

In this study, we investigated autophagy, glial activation status, and corticotropin releasing factor (CRF) signaling in the brains of mice after 5 days of sleep fragmentation (SF). Three different brain regions including the striatum, hippocampus, and frontal cortex were selected for examination based on roles in sleep regulation and sensitivity to sleep disruption. For autophagy, we monitored the levels of various autophagic induction markers including beclin1, LC3II, and p62 as well as the levels of lysosomal associated membrane protein 1 and 2 (LAMP1/2) and the transcription factor EB (TFEB) which are critical for lysosome function and autophagy maturation stage.

Educational Case: Neisseria Meningitis.

http://journals.sagepub.com/doi/10.

Basolateral Amygdala Regulates EEG Theta-activity During Rapid Eye Movement Sleep.

Pharmacological and optogenetic studies have demonstrated that the basolateral amygdala (BLA) plays a pivotal role in regulating fear-conditioned changes in sleep, in particular, rapid eye movement sleep (REM). However, the linkage between BLA and REM regulation has been minimally examined. In this study, we optogenetically activated or inhibited BLA selectively during spontaneous REM, and determined the effects on REM amounts and on hippocampus regulated EEG-theta (θ) activity.

MicroRNAs in Basolateral Amygdala Associated with Stress and Fear Memories Regulate Rapid Eye Movement Sleep in Rats.

Stress-related sleep disturbances are distressing clinical symptoms in posttraumatic stress disorder patients. Intensely stressful events and their memories change rapid eye movement (REM) sleep in animal models. REM sleep varies with individual differences of stress resilience or vulnerability.