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Neonatal hyperoxia in mice triggers long-term cognitive deficits via impairments in cerebrovascular function and neurogenesis.

Marissa A Lithopoulos | Xavier Toussay | Shumei Zhong | Liqun Xu | Shamimunisa B Mustafa | Julie Ouellette | Moises Freitas-Andrade | Cesar H Comin | Hayam A Bassam | Adam N Baker | Yiren Sun | Michael Wakem | Alvaro G Moreira | Cynthia L Blanco | Arul Vadivel | Catherine Tsilfidis | Steven R Seidner | Ruth S Slack | Diane C Lagace | Jing Wang | Baptiste Lacoste | Bernard Thébaud
The Journal of clinical investigation | 2022

Preterm birth is the leading cause of death in children under 5 years of age. Premature infants who receive life-saving oxygen therapy often develop bronchopulmonary dysplasia (BPD), a chronic lung disease. Infants with BPD are at a high risk of abnormal neurodevelopment, including motor and cognitive difficulties. While neural progenitor cells (NPCs) are crucial for proper brain development, it is unclear whether they play a role in BPD-associated neurodevelopmental deficits. Here, we show that hyperoxia-induced experimental BPD in newborn mice led to lifelong impairments in cerebrovascular structure and function as well as impairments in NPC self-renewal and neurogenesis. A neurosphere assay utilizing nonhuman primate preterm baboon NPCs confirmed impairment in NPC function. Moreover, gene expression profiling revealed that genes involved in cell proliferation, angiogenesis, vascular autoregulation, neuronal formation, and neurotransmission were dysregulated following neonatal hyperoxia. These impairments were associated with motor and cognitive decline in aging hyperoxia-exposed mice, reminiscent of deficits observed in patients with BPD. Together, our findings establish a relationship between BPD and abnormal neurodevelopmental outcomes and identify molecular and cellular players of neonatal brain injury that persist throughout adulthood that may be targeted for early intervention to aid this vulnerable patient population.

Pubmed ID: 36136598

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This is a list of tools and resources that we have found mentioned in this publication.


Fiji (tool)

RRID:SCR_002285

Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.

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RRID:SCR_002964

International functional genomics data collection generated from microarray or next-generation sequencing (NGS) platforms. Repository of functional genomics data supporting publications. Provides genes expression data for reuse to the research community where they can be queried and downloaded. Integrated with the Gene Expression Atlas and the sequence databases at the European Bioinformatics Institute. Contains a subset of curated and re-annotated Archive data which can be queried for individual gene expression under different biological conditions across experiments. Data collected to MIAME and MINSEQE standards. Data are submitted by users or are imported directly from the NCBI Gene Expression Omnibus.

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RRID:SCR_004286

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neurosphere (tool)

RRID:SCR_005478

This blog belongs to me, Dave J Hayes PhD, a Neuroscientist at the University of Ottawa''s Institute of Mental Health Research. My research focuses on the neuroscience of motivation and emotion particularly regarding how brains and people respond to aversive and rewarding things in their environment. A neurosphere is a free-floating group of neural stem cells which can multiply, outside of their natural environment, and retain the ability to differentiate into functional brain cells. I don''t work on neurospheres. However, i like the metaphor of a group of people coming together, outside of their natural environment, through their interest in all things neuro which, incidentally, is everything. The sphere of human thought.

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RRID:SCR_007370

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RRID:SCR_008058

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NumPy (tool)

RRID:SCR_008633

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ImageScope (tool)

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C57BL/6J (tool)

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RRID:SCR_021832

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