Effects of Repeated Early-life Anesthesia Exposure on Visual System Development in Mice
Year: 2025
Type: article
Abstract: BACKGROUND: General anesthesia is administered to millions of children annually, yet its long-term effects on neurodevelopment remain a concern. It was previously reported that even a single early exposure to general anesthesia for minor surgery impairs visual attention in children. This study investigates the effects of early repeated general anesthesia exposure on visual system maturation in mice and explores the role of tissue-type plasminogen activator in mediating these effects during development. METHODS: Male SWISS and C57BL/6J mice (wild-type or deficient for tissue-type plasminogen activator) were exposed to general anesthesia with 1.3% isoflurane in 50% oxygen for 90 min per day from postnatal days 4 to 10. Control animals received 50% oxygen alone. Visual system integrity and inflammation were assessed at postnatal day 15 and at 6 weeks using behavioral tests, high-resolution imaging, and immunohistochemistry. In SWISS mice, circulating tissue-type plasminogen activator levels were measured using a biochemical approach, and neurovascular coupling was evaluated by functional ultrasound imaging. RESULTS: Early repeated general anesthesia exposure delayed eyelid opening (median postnatal day 13 [95% CI, 0.52 to 1.45] vs. postnatal day 15 [95% CI, 0.62 to 1.92]; P < 0.0001), caused lasting visual function deficits (depth perception and oculomotor reflex), and reduced retinal (0.2627 ± 0.04 mm vs. 0.1667 ± 0.03 mm; P < 0.0001) and primary visual cortex thickness (0.8000 ± 0.08 mm vs. 0.7282 ± 0.05 mm; P = 0.0235). Notably, lower circulating tissue-type plasminogen activator levels were observed in general anesthesia-exposed SWISS mice (11.580 ± 2.19 ng/ml vs. 7.654 ± 1.31 ng/ml; P = 0.0082). Tissue-type plasminogen activator-deficient mice exhibited attenuated or absent general anesthesia-induced visual alterations. CONCLUSIONS: These findings indicate that early repeated exposure to general anesthesia disrupts visual system maturation in mice and suggest that altered tissue-type plasminogen activator pathways may contribute to these effects, identifying tissue-type plasminogen activator as a potential marker of anesthesia-related neurodevelopmental vulnerability. Additional experimental work will be required to further support this association and clarify its underlying mechanisms.
Source: Anesthesiology
Authors: Célia Seillier, Amandine Élodie Bonnet, Shahad Albadri, Nicolas Poirel, Gilles Orliaguet, Denis Vivien, Jean-Philippe Salaün
Institutions: Inserm, University of Oslo, Normandie Université, Cyceron, Physiopathologie et imagerie des troubles neurologiques, Université de Caen Normandie, Centre National de la Recherche Scientifique, Université Paris Sciences et Lettres, Physique pour la médecine Paris, ESPCI Paris, Institut de la Vision, Sorbonne Université, Université Paris Cité, Laboratoire de Psychologie du Développement et de L’Education de l’enfant, Hôpital Necker-Enfants Malades, Assistance Publique – Hôpitaux de Paris, Pharmacologie et évaluation thérapeutiques chez l'enfant et la femme enceinte, Centre Hospitalier Universitaire de Caen Normandie
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W4417015347