β3‐Adrenoceptor Agonism to Mimic the Biological Effects of Intrauterine Hypoxia: Taking Great Strides Toward a Pharmacological Artificial Placenta DOI Creative Commons
Luca Filippi, Francesca Innocenti, Francesca Pascarella

и другие.

Medicinal Research Reviews, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 27, 2024

ABSTRACT At different stages of life, from embryonic to postnatal, varying oxygen concentrations modulate cellular gene expression by enhancing or repressing hypoxia‐inducible transcription factors. During embryonic/fetal these genes encode proteins involved in adapting a low‐oxygen environment, including the induction specific enzymes related glycolytic metabolism, erythropoiesis, angiogenesis, and vasculogenesis. However, fluctuate during intrauterine enabling tissue‐specific differentiation processes. Fetal well‐being is thus closely linked physiological benefits dynamically hypoxic environment. Premature birth entails precocious exposure immature fetus more oxygen‐rich environment compared womb. As result, preterm newborns face condition relative hyperoxia, which alters postnatal development organs contributes prematurity‐related diseases. until recently, molecular mechanism high tension normal fetal remained unclear. In this review, we discuss research trajectory followed our group, suggests that early relatively hyperoxic may impair neonates due reduced β 3 ‐adrenoceptor. Additionally, explore how impairments could be prevented through pharmacological stimulation remaining β3‐adrenoceptors. Recent preclinical studies demonstrate ‐adrenoceptor can decouple hyperoxia its harmful effects, offering glimpse possibility recreating conditions typical even after premature birth.

Язык: Английский

Severity of bronchopulmonary dysplasia and characteristics of neuro-motor development prior to acquisition of independent walking in very preterm and/or very low-birth-weight infants: A retrospective cohort study in a children's medical centre in Japan DOI

Kazunori Mine,

Hirotaka Gima,

Shoko Sasao

и другие.

Early Human Development, Год журнала: 2025, Номер 203, С. 106225 - 106225

Опубликована: Фев. 20, 2025

Язык: Английский

Процитировано

0

Prenatal inflammation exacerbates hyperoxia-induced neonatal brain injury DOI Creative Commons
Meray Serdar,

K. Walther,

Markus Gallert

и другие.

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Фев. 28, 2025

Abstract Background Premature born infants are at high risk to develop white matter injury (WMI). Hyperoxia and perinatal inflammation main factors for preterm birth associated brain injury. To date the majority of experimental studies have focused on isolated insults. However, clinically, WMI is a multifactorial disorder caused by variety triggers. establish clinically relevant rodent model WMI, we combined prenatal with postnatal hyperoxia investigate individual, additive or synergistic effects inflammatory processes, myelination grey development. Methods At embryonic day 20, pregnant Wistar rat dams received either single intraperitoneal injection 100 µg/ kg lipopolysaccharide (LPS) sodium chloride. Offspring were exposed (80% O 2 ) normoxia (21% from 3 5. Animals sacrificed immediately after 6 days later, corresponding term-equivalent age. White development neuroinflammatory responses investigated cellular molecular levels applying immunohistochemistry, western blotting, real time PCR in tissues multiplex protein expression analysis serum samples. Results Prenatal resulted reduced body weight length offspring, accompanied increased leptin term equivalent The altered parameters, like weight, decreased volume, thinning deep cortical layers hypomyelination. As potential underlying mechanisms, identified severe deficits an microglia activation elevated cytokine tissues, while peripheral reduced. Interestingly, size mainly mediated LPS, independent hyperoxia, oligodendrocyte degeneration was induced inflammation. pathological changes, including size, deficits, expression, detected. Conclusion results aggravated compared insults, making it ideal improve our understanding complex pathophysiology evaluate urgently needed therapies.

Язык: Английский

Процитировано

0

Beta-3 Adrenoceptor Agonism Protects the Enteric Nervous Tissue Against Hyperoxia-Induced Damage DOI Creative Commons
Patrizia Nardini, Luca Filippi, Virginia Zizi

и другие.

Cells, Год журнала: 2025, Номер 14(7), С. 475 - 475

Опубликована: Март 21, 2025

The beta-3 adrenergic receptor (β3-AR), whose expression is modulated by oxygen levels, was found to play a key role in organ maturation, and its agonism reported mitigate hyperoxia-induced large bowel damage preventing hypoplasia, preserving epithelial integrity, vascularization, the neurochemical coding colonic myenteric plexus. This study explored effects of β3-AR hyperoxia-related alterations on ileal enteric nervous system (ENS). Sprague–Dawley rat pups were reared under normoxia or hyperoxia (85%) during first two weeks after birth treated not with agonist BRL37344 at 1, 3, 6 mg/kg. Hyperoxia caused an imbalance inhibitory nitrergic excitatory cholinergic neurons both submucosal plexuses decreased amounts plexus that S100β+ GFAP+ glial cells Administration 3 mg/kg preserved neuronal chemical partially prevented loss cells, while it did counteract loss. Our findings indicate potential as new therapeutic strategy for ENS alterations.

Язык: Английский

Процитировано

0

Caffeine: The Story beyond Oxygen-Induced Lung and Brain Injury in Neonatal Animal Models—A Narrative Review DOI Creative Commons
Stefanie Endesfelder

Antioxidants, Год журнала: 2024, Номер 13(9), С. 1076 - 1076

Опубликована: Сен. 3, 2024

Caffeine is one of the most commonly used drugs in intensive care to stimulate respiratory control mechanisms very preterm infants. Respiratory instability, due degree immaturity at birth, results apnea prematurity (AOP), hyperoxic, hypoxic, and intermittent hypoxic episodes. Oxidative stress cannot be avoided as a direct reaction leads neurological developmental deficits even higher prevalence diseases further development premature Due proven antioxidant effect caffeine early use, largely protective effects on clinical outcomes can observed. This also impressively observed experimental studies application oxidative stress-adapted rodent models damage developing brain lungs. However, shows undesirable outside these oxygen toxicity injury models. review hypoxic/hypoxic-ischemic, models, but negative organism when administered without exogenous stress. The narrative analysis benefits cerebral pulmonary infant supports use should given critical consideration considering treatment beyond recommended corrected gestational age.

Язык: Английский

Процитировано

3

Unveiling the Emerging Role of Extracellular Vesicle–Inflammasomes in Hyperoxia-Induced Neonatal Lung and Brain Injury DOI Creative Commons
Karen Young, Merline Benny, Augusto F. Schmidt

и другие.

Cells, Год журнала: 2024, Номер 13(24), С. 2094 - 2094

Опубликована: Дек. 18, 2024

Extremely premature infants are at significant risk for developing bronchopulmonary dysplasia (BPD) and neurodevelopmental impairment (NDI). Although BPD is a predictor of poor outcomes, it currently unknown how contributes to brain injury long-term NDI in pre-term infants. Extracellular vesicles (EVs) small, membrane-bound structures released from cells into the surrounding environment. EVs involved inter-organ communication diverse pathological processes. Inflammasomes large, multiprotein complexes that part innate immune system responsible triggering inflammatory responses cell death. Apoptosis-associated speck-like protein containing caspase recruitment domain (ASC) pivotal inflammasome assembly activating caspase-1. Activated caspase-1 cleaves gasdermin D (GSDMD) release 30 kD N-terminal can form membrane pores, leading lytic death, also known as pyroptosis. cleave pro-IL-1β pro-IL-18 their active forms, which be rapidly through GSDMD pores induce inflammation. Recent evidence has emerged activation inflammasomes associated with neonatal lung injury, inhibition reduces hyperoxia-induced injury. Additionally, multiple studies have demonstrated hyperoxia stimulates lung-derived contain cargos. Adoptive transfer these circulation normal mice rats induces This review focuses on EV–inflammasomes’ roles mediating lung-to-brain crosstalk via EV-dependent EV-independent mechanisms critical BPD, pathogenesis. EV–inflammasomes will discussed potential therapeutic targets

Язык: Английский

Процитировано

1

MicroRNA Expression Profiles in the Neonatal Rat Hippocampus Exposed to Normobaric Hyperoxia DOI Open Access
Yong Xia, T F Liu, Ruolin Zhang

и другие.

Open Journal of Pediatrics, Год журнала: 2024, Номер 14(06), С. 1038 - 1049

Опубликована: Янв. 1, 2024

Язык: Английский

Процитировано

0

β3‐Adrenoceptor Agonism to Mimic the Biological Effects of Intrauterine Hypoxia: Taking Great Strides Toward a Pharmacological Artificial Placenta DOI Creative Commons
Luca Filippi, Francesca Innocenti, Francesca Pascarella

и другие.

Medicinal Research Reviews, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 27, 2024

ABSTRACT At different stages of life, from embryonic to postnatal, varying oxygen concentrations modulate cellular gene expression by enhancing or repressing hypoxia‐inducible transcription factors. During embryonic/fetal these genes encode proteins involved in adapting a low‐oxygen environment, including the induction specific enzymes related glycolytic metabolism, erythropoiesis, angiogenesis, and vasculogenesis. However, fluctuate during intrauterine enabling tissue‐specific differentiation processes. Fetal well‐being is thus closely linked physiological benefits dynamically hypoxic environment. Premature birth entails precocious exposure immature fetus more oxygen‐rich environment compared womb. As result, preterm newborns face condition relative hyperoxia, which alters postnatal development organs contributes prematurity‐related diseases. until recently, molecular mechanism high tension normal fetal remained unclear. In this review, we discuss research trajectory followed our group, suggests that early relatively hyperoxic may impair neonates due reduced β 3 ‐adrenoceptor. Additionally, explore how impairments could be prevented through pharmacological stimulation remaining β3‐adrenoceptors. Recent preclinical studies demonstrate ‐adrenoceptor can decouple hyperoxia its harmful effects, offering glimpse possibility recreating conditions typical even after premature birth.

Язык: Английский

Процитировано

0