Corticosteroid Treatment During Sepsis Alters Hippocampal Function in Male and Female Survivors.

Background: Millions of sepsis survivors annually face neuropsychiatric sequelae of their illness. Corticosteroids are frequently administered for sepsis, and their use improves neuropsychiatric outcomes, but the mechanisms are unknown. In light of prior work that has shown persistent inflammation in sepsis survivors, we hypothesized that short-term corticosteroid treatment during illness would reverse the long-term impact of sepsis on inflammatory gene expression in the hippocampus and rescue associated changes to affective behaviors. Methods: Male and female mice underwent cecal ligation and puncture or a sham surgery to induce acute infection and were treated for 5 days with corticosterone or vehicle. Starting 2 weeks after the surgery, we performed functional phenotyping in the survivor mice followed by hippocampal RNA sequencing to identify underlying mechanisms. Results: Long-term cecal ligation and puncture survivors exhibited anxiety-like behavior, increased central hypothalamic-pituitary-adrenal axis activity, and persistent systemic and neuroinflammation. Corticosterone treatment during illness did not reverse anxiety-like behavior or inflammation in survivors. Instead, corticosterone treatment impaired object memory and increased active coping behavior in females. History of corticosterone treatment influenced the expression of >10% of detectable transcripts in the dorsal and ventral hippocampus, including a coordinated downregulation of activity-dependent genes. Conclusions: Corticosterone treatment during sepsis impaired memory formation in survivors and caused a lasting decrease in hippocampal neural activity, which could underlie its effect on memory. Future studies should focus on how this lasting effect of corticosteroid treatment on hippocampal activity and memory translates into improved neuropsychiatric outcomes in human sepsis survivors.

Corticosterone enhances formation of non-fear but not fear memory during infectious illness.

Introduction: Survivors of critical illness are at high risk of developing post-traumatic stress disorder (PTSD) but administration of glucocorticoids during the illness can lower that risk. The mechanism is not known but may involve glucocorticoid modulation of hippocampal- and amygdala-dependent memory formation. In this study, we sought to determine whether glucocorticoids given during an acute illness influence the formation and persistence of fear and non-fear memories from the time of the illness. Methods: We performed cecal ligation and puncture in male and female mice to induce an acute infectious illness. During the illness, mice were introduced to a neutral object in their home cage and separately underwent contextual fear conditioning. We then tested the persistence of object and fear memories after recovery. Results: Glucocorticoid treatment enhanced object discrimination but did not alter the expression of contextual fear memory. During context re-exposure, neural activity was elevated in the dentate gyrus irrespective of fear conditioning. Conclusions: Our results suggest that glucocorticoids given during illness enhance hippocampal-dependent non-fear memory processes. This indicates that PTSD outcomes in critically ill patients may be improved by enhancing non-fear memories from the time of their illness.

Corticosterone enhances formation of non-fear but not fear memory during infectious illness.

Survivors of critical illness are at high risk of developing post-traumatic stress disorder (PTSD) but administration of glucocorticoids during the illness can lower that risk. The mechanism is not known but may involve glucocorticoid modulation of hippocampal- and amygdalar-dependent memory formation. In this study, we sought to determine whether glucocorticoids given during an acute illness influence the formation and persistence of fear and non-fear memories from the time of the illness. We performed cecal ligation and puncture in male and female mice to induce an acute infectious illness. During the illness, mice were introduced to a neutral object in their home cage and separately underwent contextual fear conditioning. We then tested the persistence of object and fear memories after recovery. Glucocorticoid treatment enhanced object discrimination but did not alter the expression of contextual fear memory. During context re-exposure, neural activity was elevated in the dentate gyrus irrespective of fear conditioning. Our results suggest that glucocorticoids given during illness enhance hippocampal-dependent non-fear memory processes. This indicates that PTSD outcomes in critically ill patients may be improved by enhancing non-fear memories from the time of their illness.

Glucocorticoids and the Brain after Critical Illness.

Treatment for critical illness typically focuses on a patient's short-term physical recovery; however, recent work has broadened our understanding of the long-term implications of illness and treatment strategies. In particular, survivors of critical illness have significantly elevated risk of developing lasting cognitive impairment and psychiatric disorders. In this review, we examine the role of endogenous and exogenous glucocorticoids in neuropsychiatric outcomes following critical illness. Illness is marked by acute elevation of free cortisol and adrenocorticotropic hormone suppression, which typically normalize after recovery; however, prolonged dysregulation can sometimes occur. High glucocorticoid levels can cause lasting alterations to the plasticity and structural integrity of the hippocampus and prefrontal cortex, and this mechanism may plausibly contribute to impaired memory and cognition in critical illness survivors, though specific evidence is lacking. Glucocorticoids may also exacerbate inflammation-associated neural damage. Conversely, current evidence indicates that glucocorticoids during illness may protect against the development of post-traumatic stress disorder. We propose future directions for research in this field, including determining the role of persistent glucocorticoid elevations after illness in neuropsychiatric outcomes, the role of systemic vs neuroinflammation, and probing unexplored lines of investigation on the role of mineralocorticoid receptors and the gut-brain axis. Progress toward personalized medicine in this area has the potential to produce tangible improvements to the lives patients after a critical illness, including Coronavirus Disease 2019.

Soil Salinity and pH Drive Soil Bacterial Community Composition and Diversity Along a Lateritic Slope in the Avon River Critical Zone Observatory, Western Australia.

Soils are crucial in regulating ecosystem processes, such as nutrient cycling, and supporting plant growth. To a large extent, these functions are carried out by highly diverse and dynamic soil microbiomes that are in turn governed by numerous environmental factors including weathering profile and vegetation. In this study, we investigate geophysical and vegetation effects on the microbial communities of iron-rich lateritic soils in the highly weathered landscapes of Western Australia (WA). The study site was a lateritic hillslope in southwestern Australia, where gradual erosion of the duricrust has resulted in the exposure of the different weathering zones. High-throughput amplicon sequencing of the 16S rRNA gene was used to investigate soil bacterial community diversity, composition and functioning. We predicted that shifts in the microbial community would reflect variations in certain edaphic properties associated with the different layers of the lateritic profile and vegetation cover. Our results supported this hypothesis, with electrical conductivity, pH and clay content having the strongest correlation with beta diversity, and many of the differentially abundant taxa belonging to the phyla Actinobacteria and Proteobacteria. Soil water repellence, which is associated with Eucalyptus vegetation, also affected beta diversity. This enhanced understanding of the natural system could help to improve future crop management in WA since the physicochemical properties of the agricultural soils in this region are inherited from laterites via the weathering and pedogenesis processes.

Mothers' Perceptions of Child Vulnerability in Previous Preterm Infants.

This research examined whether the same predictive variables of mothers'perceptions of child vulnerability are present for extremely low birth-weight (ELBW) and very low birth-weight (VLBW) infants. Data were collected using 120 infants and 119 mothers. In ELBW infants, days until first bottle feeding, feeding problems, and feeding practices accounted for 69.9% of the variance (p < .001) at four months; feeding problems 49.9% (p < .001) at six months; and days until the first bottle feeding and feeding problems were 41.9% (p < .001) at twelve months. In the VLBW infants, feeding problems and length of stay accounted for 46.9% of the variance (p < .001) at four months; infant length of stay was 15.1% (p < .001) at six months; and there was no significance at twelve months. Mothers' perceptions of child vulnerability can be predicted at four, six and twelve months. The predictive variables may depend on the birth weight category of the infant.

Catch-up growth for the extremely low birth weight infant.

PURPOSE: This retrospective chart review describes the growth of extremely low birth weight (ELBW) infants after discharge from the neonatal intensive care unit. DESIGN: A descriptive design was used to collect data from 60 hospital records. RESULTS: Gains were noted between assessment periods (discharge--6 months and 6-12 months) (t = 4.57, t = 5.60, t = 10.77, p < 0.001) for weight, length, and head circumference, respectively. A negative change in weight (z = -1.9; CI = -3.1, -0.66) within the discharge to 6-month assessment period and a positive change in length (z = 0.54, CI = 0.05, 1.04) within the 6 to 12-month assessment were noted. Each assessment was significantly below the 50th percentile of full-term infants with weight at the 7th percentile at 12 months. DISCUSSION: The ELBW infants showed gains relative to the full-term infant but lagged behind on each growth parameter at each assessment.