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The dynamic duo: Decoding the roles of hypoxia-inducible factors in neonatal hypoxic-ischemic brain injury.

Exp Neurol

January 2025

Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, United States of America; Child Health Research Institute, Omaha, NE, United States of America; Division of Neonatology, Children's Nebraska, Omaha, NE, United States of America. Electronic address:

Neonatal hypoxic-ischemic encephalopathy (HIE) results in considerable mortality and neurodevelopmental disability, with a particularly high disease burden in low- and middle-income countries. Improved understanding of the pathophysiology underlying this injury could allow for improved diagnostic and therapeutic options. Specifically, hypoxia-inducible factors (HIF-1α and HIF-2α) likely play a key role, but that role is complex and remains understudied.

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Introduction: Chronic fetal hypoxia is commonly associated with fetal growth restriction and can predispose to respiratory disease at birth and in later life. Antenatal antioxidant treatment has been investigated to overcome the effects of oxidative stress to improve respiratory outcomes. We aimed to determine if the effects of chronic fetal hypoxia and antenatal antioxidant administration persist in the lung in early adulthood.

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Introduction: In high-altitude cities located above 2,500 m, hospitals face a concerning mortality rate of over 50% among intensive care unit (ICU) patients with acute respiratory distress syndrome (ARDS). This elevated mortality rate is largely due to the absence of altitude-specific medical protocols that consider the unique physiological adaptations of high-altitude residents to hypoxic conditions. This study addresses this critical gap by analyzing demographic, clinical, sex-specific, and preclinical data from ICUs in Bogotá, Colombia (2,650 m) and El Alto, Bolivia (4,150 m).

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Introduction: 7,8-Dihydroxyflavone (7,8-DHF) is a promising translational therapy in several brain injury models, including the neonatal hypoxia-ischemia (HI) model in mice. However, the neuroprotective effect of 7,8-DHF was only observed in female, but not male, neonatal mice with HI brain injury. It is unknown whether HI-induced physiological changes affect brain distribution of 7,8-DHF differently for male versus female mice.

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Background: Interleukin-6 (IL-6) represents one of the main molecules involved in inflammatory responses, which can be altered in either patients with cognitive impairment or obstructive sleep apnea (OSA). The present study aimed to evaluate serum IL-6 levels and cognitive performance in patients with severe OSA (Apnea-Hypopnea Index - AHI >30/h).

Methods: Thirty patients with severe OSA were compared to 15 controls similar in age, sex, and Body Mass Index.

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