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We investigated plasma concentrations of adrenocorticotropic hormone (ACTH), corticosterone and serotonin in juvenile and adult rats, as well as raphe serotonin levels and behavioral responses in the open field and elevated plus maze tests in adult rats, exposed to three sessions of neonatal hypobaric hypoxia (360 mm Hg, 2 h each, once a day) within days 8–10 postpartum. This noninvasive rat model of neonatal hypoxia (NH) simulates mild perinatal hypoxic injury in human fetuses and premature infants. At 3 months of age, NH-exposed rats exhibited reduced exploratory behavior and increased anxiety in both behavioral tests, accompanied by decreased serotonin levels in the raphe nuclei. In adult NH-exposed rats, plasma corticosterone and serotonin levels remained unaltered, while ACTH levels showed a significant decrease. Our findings suggest that early postnatal hypoxic stress disrupts the serotoninergic system and modifies the hypothalamic–pituitary–adrenocortical axis, leading to long-lasting behavioral deficits in adult rats. [ABSTRACT FROM AUTHOR]

Aims: To assess the maturational status of the brainstem auditory pathway in babies with apnoea of prematurity (AOP) at 33-34 weeks of postmenstrual age (PMA), an important time landmark at which AOP is resolved in most cases., Study Design: Compare brainstem auditory maturation between very preterm babies with AOP and those without AOP (non-AOP) at the same PMA 33-34 weeks to define differences., Results: The AOP group showed significantly longer latencies of waves III and V latency than the non-AOP group (p < 0.05 and 0.01). The I-V interval in the AOP group was significantly longer than in the non-AOP group (p < 0.001). The same was true for the I-III and III-V intervals (p < 0.001 and 0.05). Wave III amplitude was significantly smaller (p < 0.05), and wave V amplitude was moderately smaller than in the non-AOP. At PMA 33 weeks, waves III and V latencies and all intervals in the AOP group were significantly longer than in the non-AOP group (p < 0.05-0.001). At PMA 34 weeks, these wave latencies and intervals in the AOP group were still significantly longer than in the non-AOP group (p < 0.05-0.01). Wave III amplitude in the AOP group was significantly smaller at both PMA 33 and 34 weeks (p < 0.05 and 0.05)., Conclusions: Brainstem auditory maturation in AOP babies is delayed at PMA 33 weeks, and remains delayed at PMA 34 weeks. These findings highlight the importance of monitoring and adequate intervention strategies during PMA 33-34 weeks in AOP babies., Competing Interests: Declaration of competing interest We have no financial relationships relevant to this article to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Microglia are described as the immune cells of the brain, their immune properties have been extensively studied since first described, however, their neural functions have only been explored over the last decade. Microglia have an important role in maintaining homeostasis in the central nervous system by surveying their surroundings to detect pathogens or damage cells. While these are the classical functions described for microglia, more recently their neural functions have been defined; they are critical to the maturation of neurons during embryonic and postnatal development, phagocytic microglia remove excess synapses during development, a process called synaptic pruning, which is important to overall neural maturation. Furthermore, microglia can respond to neuronal activity and, together with astrocytes, can regulate neural activity, contributing to the equilibrium between excitation and inhibition through a feedback loop. Hypoxia at birth is a serious neurological condition that disrupts normal brain function resulting in seizures and epilepsy later in life. Evidence has shown that microglia may contribute to this hyperexcitability after neonatal hypoxia. This review will summarize the existing data on the role of microglia in the pathogenesis of neonatal hypoxia and the plausible mechanisms that contribute to the development of hyperexcitability after hypoxia in neonates. This article is part of the Special Issue on "Microglia". • Microglia are critical to the maturation of neurons during development. • Microglia respond to neuronal activity and regulate neural activity. • Hypoxia at birth inducesseizures and epilepsy later in life. • Microglia activation may contribute to the hyperexcitability. [ABSTRACT FROM AUTHOR]

Ambroxol, a commonly used mucolytic agent, has been extensively studied for its clinical effectiveness in managing respiratory conditions in pediatric and adult patients. The existing body of research on ambroxol demonstrates its safety and efficacy. However, its potential role in preventing and treating neonatal diseases still needs to be explored. This scoping review aims to shed light on the unexplored potential of ambroxol, particularly its applications in perinatal and neonatal care. We aim to offer valuable insights for healthcare professionals, researchers, and academics, thus presenting a positive perspective. Key scientific databases such as Google Scholar, PubMed, Cochrane Library, and Europe PMC were meticulously searched for relevant literature on ambroxol in perinatal and neonatal medicine. Gray literature was also surveyed, and the search encompassed all study designs and languages up to June 2024. Furthermore, citations and reference lists of relevant articles were scrutinized to identify additional pertinent literature. Ambroxol has demonstrated promising effects in preventing and managing respiratory distress syndrome (RDS). It can enter the placental circulation and rapidly build up in human lung tissue to a much greater extent than in plasma. It promotes fetal lung maturation, surfactant production, and alveolar expansion. Numerous studies have demonstrated the efficacy of antenatal and postnatal ambroxol in the prevention and treatment of RDS. Ambroxol has the potential to be administered intravenously or through nebulization, offering the hopeful possibility of reducing the high failure rate typically associated with non-invasive ventilation in extremely preterm infants, instilling a sense of hope and optimism about the potential of ambroxol. It also shows potential in treating bronchopulmonary dysplasia, meconium aspiration syndrome, and neonatal infections. Ambroxol has been observed to assist in the closure of patent ductus arteriosus in preterm infants by inhibiting vasodilator agents such as nitric oxide and exerting vasoconstrictive properties. However, these biological actions may raise concerns regarding the potential induction of pulmonary hypertension and an increased risk of necrotizing enterocolitis. The present scoping review also examines the clinical evidence and the potential of ambroxol in reducing the incidence of intraventricular hemorrhage in preterm infants. Ambroxol may have potential analgesic properties in managing neonatal pain, and as it can penetrate the blood-brain barrier, it suggests potential neuroprotective properties. These properties may encompass the modulation of microglial activation and the antagonistic impact on glutamate receptors. Ambroxol's attributes could contribute to a decreased susceptibility to neurological complications and have demonstrated anticonvulsant effects in preclinical studies. While low-to-moderate-quality evidence indicates potential applications of ambroxol in neonatal care, further research is needed to determine the drug's optimal dosing, timing, and safety profiles in this patient population. We need to investigate ambroxol's potential synergistic effects with antenatal steroids. Exploration is required to assess ambroxol's potential in reducing the high failure rate associated with non-invasive respiratory support for RDS. Lastly, comprehensive studies on the long-term neurodevelopmental outcomes of neonates exposed to ambroxol are essential., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Al-Abdi et al.)