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Neurobehavioral Assessments in a Mouse Model of Neonatal Hypoxic-ischemic Brain Injury
Published on: November 24, 2017
Environmental enrichment increases the GFAP+ stem cell pool and reverses hypoxia-induced cognitive deficits in
Natalina Salmaso1, John Silbereis, Mila Komitova
1Child Study Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Insights
Environmental enrichment significantly improves recovery from perinatal hypoxic injury in very low birth weight (VLBW) infants. This approach boosts stem cell survival and proliferation, enhancing neurogenesis and long-term neurological outcomes.
Area of Science:
- Neuroscience
- Developmental Biology
- Environmental Psychology
Background:
- Very low birth weight (VLBW) infants face risks of chronic hypoxic injury, leading to neurological and behavioral issues.
- Environmental enrichment shows promise in animal models of adult brain injury, but its effects on developmental brain injury are less understood.
- Early environment significantly impacts neurological outcomes in VLBW cohorts.
Purpose of the Study:
- To investigate the impact of environmental enrichment on recovery from perinatal hypoxic injury.
- To explore the neurobiological mechanisms underlying environmental enrichment's effects on brain development after hypoxia.
Main Methods:
- Utilized a genetic fate-mapping model to track GFAP+ astroglial cells.
- Induced perinatal hypoxic injury in a mouse model.
- Implemented environmental enrichment protocols post-injury.
- Assessed behavioral and neurobiological recovery, including hippocampal neurogenesis.
Main Results:
- Hypoxic injury increased the neuronal fate of astroglial cells.
- Environmental enrichment expanded the stem cell pool via increased proliferation and survival.
- Combined hypoxia and enrichment had an additive effect on hippocampal neurogenesis from astroglia.
- A significant increase in neurons derived from GFAP+ cells was observed in adulthood.
Conclusions:
- Environmental enrichment is a potent strategy for enhancing behavioral and neurobiological recovery from perinatal hypoxic injury.
- Enrichment positively modulates the neural stem cell pool, promoting neurogenesis.
- Targeting the early environment holds significant therapeutic potential for improving outcomes in VLBW individuals.
Abstract:
Premature children born with very low birth weight (VLBW) can suffer chronic hypoxic injury as a consequence of abnormal lung development and cardiovascular abnormalities, often leading to grave neurological and behavioral consequences. Emerging evidence suggests that environmental enrichment improves outcome in animal models of adult brain injury and disease; however, little is known about the impact of environmental enrichment following developmental brain injury. Intriguingly, data on socio-demographic factors from longitudinal studies that examined a number of VLBW cohorts suggest that early environment has a substantial impact on neurological and behavioral outcomes. In the current study, we demonstrate that environmental enrichment significantly enhances behavioral and neurobiological recovery from perinatal hypoxic injury. Using a genetic fate-mapping model that allows us to trace the progeny of GFAP+ astroglial cells, we show that hypoxic injury increases the proportion of astroglial cells that attain a neuronal fate. In contrast, environmental enrichment increases the stem cell pool, both through increased stem cell proliferation and stem cell survival. In mice subjected to hypoxia and subsequent enrichment there is an additive effect of both conditions on hippocampal neurogenesis from astroglia, resulting in a robust increase in the number of neurons arising from GFAP+ cells by the time these mice reach full adulthood.
