Authors: Seillier C et al.
Journal: Anesthesiology, December 4, 2025. DOI: 10.1097/ALN.0000000000005879
Summary
This preclinical study examined the effects of repeated early-life exposure to general anesthesia on visual system development in mice and explored the role of tissue-type plasminogen activator (tPA) as a potential mechanistic mediator. Given ongoing concerns about neurodevelopmental consequences of pediatric anesthesia—and prior human data linking even single early anesthetic exposure to impaired visual attention—the authors investigated whether repeated exposures during a critical developmental window would produce lasting structural and functional changes.
Neonatal mice were exposed to isoflurane anesthesia daily from postnatal day 4 to 10, a period corresponding to rapid visual system maturation. Compared with control animals, repeatedly anesthetized mice demonstrated delayed eyelid opening, persistent deficits in depth perception and oculomotor reflexes, and measurable thinning of both the retina and primary visual cortex that persisted into adolescence. These findings indicate a disruption of normal visual circuit development rather than a transient maturational delay.
Mechanistically, anesthetic exposure was associated with reduced circulating levels of tissue-type plasminogen activator, a molecule involved in synaptic plasticity, neurovascular coupling, and developmental remodeling. Importantly, mice genetically deficient in tPA showed markedly attenuated or absent visual deficits after anesthesia exposure, suggesting that tPA-dependent pathways contribute to vulnerability during early neurodevelopment. Functional imaging further indicated impaired neurovascular coupling following anesthesia.
Overall, the study provides experimental evidence that repeated neonatal anesthesia exposure can disrupt visual system maturation and identifies tPA signaling as a potential biomarker and mechanistic contributor to anesthesia-related neurodevelopmental effects.
Key Points
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Repeated early-life exposure to isoflurane disrupted visual system development in mice.
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Anesthesia-exposed mice showed delayed eyelid opening and persistent visual function deficits.
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Structural thinning of the retina and primary visual cortex persisted into later life.
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Circulating tissue-type plasminogen activator levels were reduced after anesthesia exposure.
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tPA-deficient mice were protected from many anesthesia-induced visual abnormalities.
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Findings suggest tPA-related pathways may mediate vulnerability to early anesthetic exposure.
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