Effects of chronic hypercapnia in the neonatal mouse lung and brain

Summary. 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 α-smooth muscle actin (α-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.