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Neurobehavioral Assessments in a Mouse Model of Neonatal Hypoxic-ischemic Brain Injury
Published on: November 24, 2017
Effects of chronic hypercapnia in the neonatal mouse lung and brain
Sumon Das1, Zhongfang Du, Shira Bassly
1Department of Pediatrics, Division of Critical Care Medicine, Albert Einstein College of Medicine and Children's Hospital at Montefiore, Bronx, New York 10467, USA.
Insights
Permissive hypercapnia may accelerate lung development in premature infants by promoting alveolar budding. However, this intervention may also increase neuronal cell injury in the developing brain.
Area of Science:
- Neonatal physiology
- Developmental biology
- Respiratory medicine
Background:
- Permissive hypercapnia is used to prevent bronchopulmonary dysplasia in premature infants.
- Previous studies showed gene expression changes in neonatal mouse lungs exposed to hypercapnia.
- The effects of hypercapnia on alveolar formation and brain development were unknown.
Purpose of the Study:
- To investigate if chronic hypercapnia accelerates alveolar formation in neonatal mouse lungs.
- To determine if chronic hypercapnia causes neuronal cell injury in the developing mouse brain.
Main Methods:
- Neonatal mice were exposed to 8% CO2 from postnatal day 2 to 7.
- Control mice were kept in room air.
- Lungs and brains were analyzed at postnatal days 4 and 7.
Main Results:
- Hypercapnia increased alpha-smooth muscle actin expression at alveolar bud tips.
- An increased number of alveolar buds was observed at postnatal day 7.
- Hypercapnic mice showed increased TUNEL-positive cells in the brain.
Conclusions:
- Chronic hypercapnia may initiate early alveolar budding in neonatal mice.
- Hypercapnia exposure might lead to increased neuronal cell injury in the developing brain.
Background:
Permissive hypercapnia is increasingly utilized in the care of premature infants to prevent bronchopulmonary dysplasia. In a previous investigation, we described gene expression changes in the neonatal mouse lung exposed to chronic hypercapnia that might contribute to lung protection and accelerated maturation. However, it is unknown whether chronic hypercapnia increases alveolar formation, nor if it has detrimental effects in other developing organs such as the brain.
Objective:
To determine whether chronic hypercapnia accelerates early alveolar formation and increases neuronal cell injury in the developing mouse lung and brain, respectively.
Design:
Mouse pups were exposed to 8% CO(2) + 21% O(2) starting at postnatal day (P) 2 until P7. Control animals were maintained in room air. Animals were sacrificed at P4 or P7, and lungs and brains were excised and analyzed.
Results:
Exposure to 8% CO(2) resulted in an increased expression of alpha-smooth muscle actin (alpha-sma) which localized to the tips of developing alveolar buds, and also an increased number of alveolar buds at P7. Importantly, hypercapnic animals also demonstrated evidence of increased TUNEL-positive cells in the brain.
Conclusions:
Exposure to chronic hypercapnia may lead to early initiation of alveolar budding in the neonatal mouse, but may also lead to increased TUNEL-positive cells in the developing brain.
