scholarly journals Effect of neonatal dexamethasone exposure on growth and neurological development in the adult rat

2004 ◽  
Vol 287 (2) ◽  
pp. R375-R385 ◽  
Author(s):  
Charles R. Neal ◽  
Gabrielle Weidemann ◽  
Mohamed Kabbaj ◽  
Delia M. Vázquez
Keyword(s):  
Open Field ◽  
Neonatal Intensive Care ◽  
Somatic Growth ◽  
Stress Axis ◽  
Human Infants ◽  
Neurodevelopmental Delay ◽  
Adult Rat ◽  
Physical Maturation ◽  
Corticosterone Response

Until recently, the synthetic glucocorticoid dexamethasone was commonly used to lessen the morbidity of chronic lung disease in premature infants. This practice diminished as dexamethasone use was linked to an increased incidence of cerebral palsy and short-term neurodevelopmental delay. Of more concern is the fact that we know little regarding dexamethasone effects on long-term neurodevelopment. To study the effects of neonatal dexamethasone exposure on long-term neurodevelopment, we have developed a rat model where newborn pups are exposed to tapering doses of dexamethasone at time points corresponding to the neurodevelopmental age when human infants are traditionally exposed to this drug in the neonatal intensive care unit. Using a within-litter design, pups were assigned to one of three groups on postnatal day 2 (P2): handled controls, saline-injected controls, and animals receiving intramuscular dexamethasone between P3 and P6. Somatic growth was decreased in dexamethasone-treated animals. Dexamethasone-treated animals demonstrated slight delays in indexes of neurodevelopment and physical maturation at P7 and P14, but not P20. In adolescence (P45), there was no difference between groups in an open field test. However, as adult dexamethasone-treated animals were less active in the open field and spent more time in closed arms of the elevated plus maze. The serum corticosterone response to crowding stress in dexamethasone-treated animals was no different from controls, but they demonstrate a delay in return of corticosterone levels to baseline. These differences in behavior and hormonal stress responsiveness suggest that neonatal dexamethasone exposure may permanently alter function of the neuroendocrine stress axis.

Effects of tapering neonatal dexamethasone on rat growth, neurodevelopment, and stress response

2002 ◽  
Vol 282 (1) ◽  
pp. R55-R63 ◽  
Author(s):  
Shelly B. Flagel ◽  
Delia M. Vázquez ◽  
Stanley J. Watson ◽  
Charles R. Neal
Keyword(s):  
Neonatal Intensive Care ◽  
Somatic Growth ◽  
Stress Axis ◽  
Increased Risk ◽  
Stress Responsiveness ◽  
Rat Growth ◽  
Nervous System Function ◽  
Corticosterone Response ◽  
Neurological Effects ◽  
Learning Impairment

Dexamethasone is commonly used to lessen the morbidity of chronic lung disease in premature infants, but little is known regarding neurological consequences of its prolonged use. To study neurological effects of dexamethasone, we have developed a rat model in which newborn pups are exposed to tapering doses of dexamethasone at a time corresponding neurodevelopmentally to human exposure in the neonatal intensive care unit. On postnatal day (PD) 2, litters were divided into three groups: 1) handled controls, 2) saline-injected animals, and 3) animals injected with tapering doses of intramuscular dexamethasone between PD 3 and 6. Somatic growth and brain weight were decreased in dexamethasone-treated animals. Dexamethasone-treated animals demonstrated delays in gross neurological development on PD 7 and 14 but not PD 20. In late adolescence ( PD 33), dexamethasone-treated animals were less active in light and dark environments, while demonstrating a blunted serum corticosterone response to a novel stress. The dissociation between behavioral and hormonal stress responsiveness suggests that neonatal dexamethasone exposure permanently alters central nervous system function, particularly within the neuroendocrine stress axis. This may lead to increased risk for learning impairment and maladaptive responses to the environment.

scholarly journals In utero exposure to protease inhibitor-based antiretroviral regimens delays growth and developmental milestones in mice

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242513
Author(s):  
Ambalika Sarkar ◽  
Kayode Balogun ◽  
Monica S. Guzman Lenis ◽  
Sebastian Acosta ◽  
Howard T. Mount ◽  
...  
Keyword(s):  
Open Field ◽  
Somatic Growth ◽  
In Utero ◽  
Developmental Milestones ◽  
Human Infants ◽  
Developmental Milestone ◽  
Negative Geotaxis ◽  
Primitive Reflexes ◽  
Olfactory Test ◽  
In Pregnancy

Antiretroviral therapy (ART) in pregnancy has dramatically reduced HIV vertical transmission rates. Consequently, there is a growing number of children that are HIV exposed uninfected (CHEUs). Studies suggest that CHEUs exposed in utero to ART may experience developmental delays compared to their peers. We investigated the effects of in utero ART exposure on perinatal neurodevelopment in mice, through assessment of developmental milestones. Developmental milestone tests (parallel to reflex testing in human infants) are reflective of brain maturity and useful in predicting later behavioral outcomes. We hypothesized that ART in pregnancy alters the in utero environment and thereby alters developmental milestone outcomes in pups. Throughout pregnancy, dams were treated with boosted-atazanavir combined with either abacavir/lamivudine (ATV/r/ABC/3TC), or tenofovir/emtricitabine (ATV/r/TDF/FTC), or water as control. Pups were assessed daily for general somatic growth and on a battery of tests for primitive reflexes including surface-righting, negative-geotaxis, cliff-aversion, rooting, ear-twitch, auditory-reflex, forelimb-grasp, air-righting, behaviors in the neonatal open field, and olfactory test. In utero exposure to either ART regimen delayed somatic growth in offspring and evoked significant delays in the development of negative geotaxis, cliff-aversion, and ear-twitch reflexes. Exposure to ATV/r/ABC/3TC was also associated with olfactory deficits in male and forelimb grasp deficits in female pups. To explore whether delays persisted into adulthood we assessed performance in the open field test. We observed no significant differences between treatment arm for males. In females, ATV/r/TDF/FTC exposure was associated with lower total distance travelled and less ambulatory time in the centre, while ATV/r/ABC/3TC exposure was associated with higher resting times compared to controls. In utero PI-based ART exposure delays the appearance of primitive reflexes that involve vestibular and sensory-motor pathways in a mouse model. Our findings suggest that ART could be disrupting the normal progress/maturation of the underlying neurocircuits and encourage further investigation for underlying mechanisms.

Improving Feeding Outcomes in the NICU: Moving From Volume-Driven to Infant-Driven Feeding

2010 ◽  
Vol 19 (3) ◽  
pp. 68-74 ◽  
Author(s):  
Catherine S. Shaker
Keyword(s):  
Intensive Care Unit ◽  
Dynamic Systems ◽  
Neonatal Intensive Care ◽  
Well Being ◽  
Dynamic Systems Theory ◽  
Feeding Problems ◽  
Care Giving ◽  
Extremely Preterm ◽  
Extremely Preterm Infants

Current research on feeding outcomes after discharge from the neonatal intensive care unit (NICU) suggests a need to critically look at the early underpinnings of persistent feeding problems in extremely preterm infants. Concepts of dynamic systems theory and sensitive care-giving are used to describe the specialized needs of this fragile population related to the emergence of safe and successful feeding and swallowing. Focusing on the infant as a co-regulatory partner and embracing a framework of an infant-driven, versus volume-driven, feeding approach are highlighted as best supporting the preterm infant's developmental strivings and long-term well-being.

Point of Care Neurosonogram in Neonates - Utility and Prognostic Value

2019 ◽  
Vol 2 ◽  
pp. 1
Author(s):  
Bhushita Lakhkar ◽  
M. M. Patil ◽  
Bhavana Lakhkar ◽  
Bhushan Lakhkar
Keyword(s):  
Neonatal Intensive Care ◽  
Point Of Care ◽  
Color Doppler ◽  
Periventricular Leukomalacia ◽  
Birth Asphyxia ◽  
Common Finding ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Doppler Study

Objective The study aimed to utilize the neurosonographic findings in neonates in early diagnosis, prediction of their long-term outcome, parental counseling, and early intervention. Methods The study was carried out in neonatal intensive care unit (NICU) of Shri BM Patil Medical College and Hospital. All preterms and term babies with neurological clinical findings were included in the study. Neurosonogram was done within first 7 days in preterms and when indicated in terms. Philips HD11XE ultrasound and color Doppler unit were used with a small footprint probe. Color Doppler images for vessels were performed for screening of vascular changes. Results A total of 215 babies were included, of which 80 (32%) were term and the rest were preterm. Mean weight of term babies was 2.8 kg and that of preterm was 1.2 kg.Among term babies, 78% showed ultrasound abnormality, and among preterm, 42%showed abnormalities. Among term babies, 60% and, among preterms, 30% had birth asphyxia. Periventricular leukomalacia was the most common and earliest finding followed by thalamic hyperechogenicity and intracranial hemorrhage. Intraventricular hemorrhage was more common in preterm babies. Other common finding in NICU was meningitis which was more common in pretrms. Among congenital anomalies, corpus callosal agenesis was more common. Conclusions Point of care ultrasonography along with Doppler study is very useful and safe to use in NICUs. It helps in diagnosis, patient management as well as prediction of many short- and long-term outcomes.

Gestational exposure to Δ9-THC impacts ovarian follicular dynamics and angiogenesis in adulthood in Wistar rats

2021 ◽  
pp. 1-5
Author(s):  
Annia A. Martínez-Peña ◽  
Kendrick Lee ◽  
James J. Petrik ◽  
Daniel B. Hardy ◽  
Alison C. Holloway
Keyword(s):  
Reproductive Health ◽  
Cannabis Sativa ◽  
Follicular Development ◽  
Angiogenic Factor ◽  
Postnatal Life ◽  
Adult Rat ◽  
Female Reproductive Health ◽  
Gestational Exposure ◽  
Follicular Dynamics

Abstract With the legalization of marijuana (Cannabis sativa) and increasing use during pregnancy, it is important to understand its impact on exposed offspring. Specifically, the effects of Δ-9-tetrahydrocannabinol (Δ9-THC), the major psychoactive component of cannabis, on fetal ovarian development and long-term reproductive health are not fully understood. The aim of this study was to assess the effect of prenatal exposure to Δ9-THC on ovarian health in adult rat offspring. At 6 months of age, Δ9-THC-exposed offspring had accelerated folliculogenesis with apparent follicular development arrest, but no persistent effects on circulating steroid levels. Ovaries from Δ9-THC-exposed offspring had reduced blood vessel density in association with decreased expression of the pro-angiogenic factor VEGF and its receptor VEGFR-2, as well as an increase in the anti-angiogenic factor thrombospondin 1 (TSP-1). Collectively, these data suggest that exposure to Δ9-THC during pregnancy alters follicular dynamics during postnatal life, which may have long-lasting detrimental effects on female reproductive health.

scholarly journals Association between confirmed congenital Zika infection at birth and outcomes up to 3 years of life

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Najeh Hcini ◽  
Yaovi Kugbe ◽  
Zo Hasina Linah Rafalimanana ◽  
Véronique Lambert ◽  
Meredith Mathieu ◽  
...  
Keyword(s):  
Neurological Impairment ◽  
In Utero ◽  
In Utero Exposure ◽  
Zikv Infection ◽  
Neurodevelopmental Delay ◽  
Systematic Testing ◽  
Brain Anomalies ◽  
Increased Risk ◽  
Structural Brain

AbstractLittle is known about the long-term neurological development of children diagnosed with congenital Zika infection at birth. Here, we report the imaging and clinical outcomes up to three years of life of a cohort of 129 children exposed to Zika virus in utero. Eighteen of them (14%) had a laboratory confirmed congenital Zika infection at birth. Infected neonates have a higher risk of adverse neonatal and early infantile outcomes (death, structural brain anomalies or neurologic symptoms) than those who tested negative: 8/18 (44%) vs 4/111 (4%), aRR 10.1 [3.5–29.0]. Neurological impairment, neurosensory alterations or delays in motor acquisition are more common in infants with a congenital Zika infection at birth: 6/15 (40%) vs 5/96 (5%), aRR 6.7 [2.2–20.0]. Finally, infected children also have an increased risk of subspecialty referral for suspected neurodevelopmental delay by three years of life: 7/11 (64%) vs 7/51 (14%), aRR 4.4 [1.9–10.1]. Infected infants without structural brain anomalies also appear to have an increased risk, although to a lesser extent, of neurological abnormalities. It seems paramount to offer systematic testing for congenital ZIKV infection in cases of in utero exposure and adapt counseling based on these results.

scholarly journals In Utero Exposure to Δ9-Tetrahydrocannabinol Leads to Postnatal Catch-Up Growth and Dysmetabolism in the Adult Rat Liver

2021 ◽  
Vol 22 (14) ◽  
pp. 7502
Author(s):  
Shelby L. Oke ◽  
Kendrick Lee ◽  
Rosemary Papp ◽  
Steven R. Laviolette ◽  
Daniel B. Hardy
Keyword(s):  
Mitochondrial Dysfunction ◽  
Animal Studies ◽  
Weight Ratio ◽  
Wistar Rat ◽  
Hepatic Function ◽  
Fetal Life ◽  
Adult Rat ◽  
Catch Up ◽  
By Catch

The rates of gestational cannabis use have increased despite limited evidence for its safety in fetal life. Recent animal studies demonstrate that prenatal exposure to Δ9-tetrahydrocannabinol (Δ9-THC, the psychoactive component of cannabis) promotes intrauterine growth restriction (IUGR), culminating in postnatal metabolic deficits. Given IUGR is associated with impaired hepatic function, we hypothesized that Δ9-THC offspring would exhibit hepatic dyslipidemia. Pregnant Wistar rat dams received daily injections of vehicular control or 3 mg/kg Δ9-THC i.p. from embryonic day (E) 6.5 through E22. Exposure to Δ9-THC decreased the liver to body weight ratio at birth, followed by catch-up growth by three weeks of age. At six months, Δ9-THC-exposed male offspring exhibited increased visceral adiposity and higher hepatic triglycerides. This was instigated by augmented expression of enzymes involved in triglyceride synthesis (ACCα, SCD, FABP1, and DGAT2) at three weeks. Furthermore, the expression of hepatic DGAT1/DGAT2 was sustained at six months, concomitant with mitochondrial dysfunction (i.e., elevated p66shc) and oxidative stress. Interestingly, decreases in miR-203a-3p and miR-29a/b/c, both implicated in dyslipidemia, were also observed in these Δ9-THC-exposed offspring. Collectively, these findings indicate that prenatal Δ9-THC exposure results in long-term dyslipidemia associated with enhanced hepatic lipogenesis. This is attributed by mitochondrial dysfunction and epigenetic mechanisms.

scholarly journals Prenatally traumatized mice reveal hippocampal methylation and expression changes of the stress-related genes Crhr1 and Fkbp5

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anne-Christine Plank ◽  
Stefan Frey ◽  
Lukas Andreas Basedow ◽  
Jalal Solati ◽  
Fabio Canneva ◽  
...  
Keyword(s):  
Stress Reactivity ◽  
Dorsal Hippocampus ◽  
Methylation Status ◽  
Stress Axis ◽  
Mrna Levels ◽  
Fk506 Binding Protein ◽  
Adult Mice ◽  
Stress Related Genes ◽  
Long Term Impact

AbstractIn our previous study, we found that prenatal trauma exposure leads to an anxiety phenotype in mouse pups, characterized by increased corticosterone levels and increased anxiety-like behavior. In order to understand the mechanisms by which aversive in utero experience leads to these long-lasting behavioral and neuroendocrine changes, we investigated stress reactivity of prenatally traumatized (PT) mice, as well as the expression and methylation levels of several key regulatory genes of the stress axis in the dorsal hippocampus (dHPC) of the PT embryo and adult mice. We detected increased corticotropin-releasing hormone receptor 1 (Crhr1) and decreased FK506 binding protein 5 (Fkbp5) mRNA levels in the left dHPC of adult PT mice. These alterations were accompanied by a decreased methylation status of the Crhr1 promoter and an increased methylation status of the Fkbp5 promoter, respectively. Interestingly, the changes in Fkbp5 and Crhr1 mRNA levels were not detected in the embryonic dHPC of PT mice. Together, our findings provide evidence that prenatal trauma has a long-term impact on stress axis function and anxiety phenotype associated with altered Crhr1 and Fkbp5 transcripts and promoter methylation.

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