The importance of including both sexes in preclinical sleep studies and analyses.

A significant effort in biomedical sciences has been made to examine relationships between sex and the mechanisms underlying various disease states and behaviors, including sleep. Here, we investigated biological sex differences in sleep using male and female C57BL/6J mice (n = 267). Physiological parameters were recorded for 48-h using non-invasive piezoelectric cages to determine total sleep, non-rapid eye movement (NREM) sleep, rapid eye movement (REM)-like sleep, and wakefulness (WAKE).

Quantifying microglial morphology: an insight into function.

Microglia are specialized immune cells unique to the central nervous system (CNS). Microglia have a highly plastic morphology that changes rapidly in response to injury or infection. Qualitative and quantitative measurements of ever-changing microglial morphology are considered a cornerstone of many microglia-centric research studies.

Sleep, inflammation, and hemodynamics in rodent models of traumatic brain injury.

Traumatic brain injury (TBI) can induce dysregulation of sleep. Sleep disturbances include hypersomnia and hyposomnia, sleep fragmentation, difficulty falling asleep, and altered electroencephalograms. TBI results in inflammation and altered hemodynamics, such as changes in blood brain barrier permeability and cerebral blood flow.

Blood-Brain Barrier Dysfunction Predicts Microglial Activation After Traumatic Brain Injury in Juvenile Rats.

Traumatic brain injury (TBI) disrupts the blood-brain barrier (BBB), which may exacerbate neuroinflammation post-injury. Few translational studies have examined BBB dysfunction and subsequent neuroinflammation post-TBI in juveniles. We hypothesized that BBB dysfunction positively predicts microglial activation and that vulnerability to BBB dysfunction and associated neuroinflammation are dependent on age at injury.

Regulation of microglial responses after pediatric traumatic brain injury: exploring the role of SHIP-1.

Introduction: Severe traumatic brain injury (TBI) is the world's leading cause of permanent neurological disability in children. TBI-induced neurological deficits may be driven by neuroinflammation post-injury. Abnormal activity of SH2 domain-containing inositol 5' phosphatase-1 (SHIP-1) has been associated with dysregulated immunological responses, but the role of SHIP-1 in the brain remains unclear.

Diffuse traumatic brain injury substantially alters plasma growth hormone in the juvenile rat.

Traumatic brain injury (TBI) can damage the hypothalamus and cause improper activation of the growth hormone (GH) axis, leading to growth hormone deficiency (GHD). GHD is one of the most prevalent endocrinopathies following TBI in adults; however, the extent to which GHD affects juveniles remains understudied. We used postnatal day 17 rats (n = 83), which model the late infantile/toddler period, and assessed body weights, GH levels, and number of hypothalamic somatostatin neurons at acute (1, 7 days post injury (DPI)) and chronic (18, 25, 43 DPI) time points.

Colony-Stimulating Factor-1 Receptor Inhibition Transiently Attenuated the Peripheral Immune Response to Experimental Traumatic Brain Injury.

To investigate microglial mechanisms in central and peripheral inflammation after experimental traumatic brain injury (TBI), we inhibited the colony-stimulating factor-1 receptor (CSF-1R) with PLX5622 (PLX). We hypothesized that microglia depletion would attenuate central inflammation acutely with no effect on peripheral inflammation. After randomization, male mice ( = 105) were fed PLX or control diets (21 days) and then received midline fluid percussion injury or sham injury.

Comparisons of quantitative approaches for assessing microglial morphology reveal inconsistencies, ecological fallacy, and a need for standardization.

Microglial morphology is used to measure neuroinflammation and pathology. For reliable inference, it is critical that microglial morphology is accurately quantified and that results can be easily interpreted and compared across studies and laboratories. The process through which microglial morphology is quantified is a key methodological choice and little is known about how this choice may bias conclusions.

Reactive morphology of dividing microglia following kainic acid administration.

The microglial response to a pathological microenvironment is hallmarked by a change in cellular morphology. Following a pathological stimulus, microglia become reactive and simultaneously divide to create daughter cells. Although a wide array of microglial morphologies has been observed, the exact functions of these distinct morphologies are unknown, as are the morphology and reactivity status of dividing microglia.

Microglia Are Necessary to Regulate Sleep after an Immune Challenge.

Microglia play a critical role in the neuroimmune response, but little is known about the role of microglia in sleep following an inflammatory trigger. Nevertheless, decades of research have been predicated on the assumption that an inflammatory trigger increases sleep through microglial activation. We hypothesized that mice ( = 30) with depleted microglia using PLX5622 (PLX) would sleep less following the administration of lipopolysaccharide (LPS) to induce inflammation.

Traumatic Brain Injury Characteristics Predictive of Subsequent Sleep-Wake Disturbances in Pediatric Patients.

The objective of this study was to determine the prevalence of sleep-wake disturbances (SWD) following pediatric traumatic brain injury (TBI), and to examine characteristics of TBI and patient demographics that might be predictive of subsequent SWD development. This single-institution retrospective study included patients diagnosed with a TBI during 2008-2019 who also had a subsequent diagnosis of an SWD. Data were collected using ICD-9/10 codes for 207 patients and included the following: age at initial TBI, gender, TBI severity, number of TBIs diagnosed prior to SWD diagnosis, type of SWD, and time from initial TBI to SWD diagnosis.

Design and Synthesis of Brain Penetrant Glycopeptide Analogues of PACAP With Neuroprotective Potential for Traumatic Brain Injury and Parkinsonism.

There is an unmet clinical need for curative therapies to treat neurodegenerative disorders. Most mainstay treatments currently on the market only alleviate specific symptoms and do not reverse disease progression. The Pituitary adenylate cyclase-activating polypeptide (PACAP), an endogenous neuropeptide hormone, has been extensively studied as a potential regenerative therapeutic.

Age-At-Injury Influences the Glial Response to Traumatic Brain Injury in the Cortex of Male Juvenile Rats.

Few translational studies have examined how age-at-injury affects the glial response to traumatic brain injury (TBI). We hypothesized that rats injured at post-natal day (PND) 17 would exhibit a greater glial response, that would persist into early adulthood, compared to rats injured at PND35. PND17 and PND35 rats ( = 75) received a mild to moderate midline fluid percussion injury or sham surgery.

The Bidirectional Relationship Between Sleep and Inflammation Links Traumatic Brain Injury and Alzheimer's Disease.

Traumatic brain injury (TBI) and Alzheimer's disease (AD) are diseases during which the fine-tuned autoregulation of the brain is lost. Despite the stark contrast in their causal mechanisms, both TBI and AD are conditions which elicit a neuroinflammatory response that is coupled with physical, cognitive, and affective symptoms. One commonly reported symptom in both TBI and AD patients is disturbed sleep.

Simultaneous Cryosectioning of Multiple Rodent Brains.

Histology and immunohistochemistry are routine methods of analysis to visualize microscopic anatomy and localize proteins within biological tissue. In neuroscience, as well as a plethora of other scientific fields, these techniques are used. Immunohistochemistry can be done on slide mounted tissue or free-floating sections.