Abstract
General anaesthesia may impose significant neurocognitive risks on the developing brain. As brain injury in preterm neonates has a particular predilection for cerebral white matter, we aimed to evaluate the effects of sevoflurane on oligodendrocyte maturation and myelination in a preterm-equivalent rat model. Two-day-old postnatal (P2) Sprague-Dawley rats were exposed to 3.3 % (approximately 1 minimum alveolar concentration [MAC]) or 4.9 % (approximately 1.5 MAC) sevoflurane for 2 h. Physiologic parameters were measured at the end of sevoflurane anaesthesia. Oligodendrocyte proliferation, maturation, and myelination were evaluated by immunofluorescence with specific markers at different time points. Open field test and Morris water maze tests were performed to access behavior changes from P29 to P36. Arterial blood gases values and blood glucose levels were within the normal physiologic range. As compared to control, 4.9 %, but not 3.3 % sevoflurane disturbed oligodendrocyte maturation at P14, resulting in hypomyelination and axonal damage in cerebral white matter at P28. Rats exposed to 4.9 %, but not 3.3 % sevoflurane showed decreased explorative activity and increased anxiety-like behaviour, as well as learning and memory impairments. Furthermore, 4.9 %, but not 3.3 % sevoflurane inhibited oligodendrocyte proliferation in the developing white matter of the rat brain at 12 h post-anaesthesia, with further evidence of widespread reactive astrogliosis. High concentration of sevoflurane (4.9 %) exposure in early postnatal rats may disrupt oligodendrocyte maturation and myelination. Our study has aimed a spotlight on the need for safe and rational use of analgesics in neonates, especially preterm infants.