Authors: Seillier C et al.
Anesthesiology. December 2025.
Summary
This preclinical study investigated the effects of repeated early-life exposure to general anesthesia on visual system development and maturation in mice, with a particular focus on the role of tissue-type plasminogen activator (tPA) as a potential mechanistic mediator. Given ongoing concerns about the long-term neurodevelopmental consequences of pediatric anesthesia, the authors aimed to explore whether repeated exposures during a critical developmental window produce persistent visual deficits.
Male SWISS and C57BL/6J mice, including both wild-type and tPA-deficient strains, were exposed to isoflurane anesthesia (1.3% in 50% oxygen) for 90 minutes daily from postnatal day 4 to 10. Control animals received oxygen alone. Visual development and neuroinflammatory markers were assessed in the early postnatal period and again in adulthood using behavioral testing, high-resolution structural imaging, immunohistochemistry, and functional ultrasound to evaluate neurovascular coupling.
Repeated anesthesia exposure resulted in delayed eyelid opening, persistent impairments in depth perception and oculomotor reflexes, and measurable structural changes in the visual system, including reduced retinal thickness and thinning of the primary visual cortex. These deficits persisted into adulthood, indicating long-lasting disruption of visual system maturation. In parallel, anesthesia-exposed SWISS mice demonstrated significantly lower circulating tPA levels and altered neurovascular coupling responses.
Importantly, mice genetically deficient in tPA showed markedly attenuated or absent anesthesia-induced visual deficits, suggesting that tPA signaling plays a contributory role in mediating anesthesia-related neurodevelopmental vulnerability. Together, these findings support a biological link between repeated early anesthesia exposure, impaired visual system development, and altered proteolytic and neurovascular pathways.
Key Points
Repeated early-life exposure to isoflurane disrupted visual system maturation in mice.
Anesthesia exposure caused persistent deficits in visual function and structural thinning of the retina and visual cortex.
Circulating tissue-type plasminogen activator levels were reduced following repeated anesthesia exposure.
tPA-deficient mice were protected from many anesthesia-induced visual alterations.
tPA signaling may represent a mechanistic pathway and potential biomarker for anesthesia-related neurodevelopmental vulnerability.
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