Sugammadex-Enhanced Neuronal Apoptosis following Neonatal Sevoflurane Exposure in Mice

Abstract

In rodents, neonatal sevoflurane exposure induces neonatal apoptosis in the brain and results in learning deficits. Sugammadex is a new selective neuromuscular blockade (NMB) binding agent that anesthesiologists can use to achieve immediate reversal of an NMB with few side effects. Given its molecular weight of 2178, sugammadex is thought to be unable to pass through the blood brain barrier (BBB). Volatile anesthetics can influence BBB opening and integrity. Therefore, we investigated whether the intraperitoneal administration of sugammadex could exacerbate neuronal damage following neonatal 2% sevoflurane exposure via changes in BBB integrity. Cleaved caspase-3 immunoblotting was used to detect apoptosis, and the ultrastructure of the BBB was examined by transmission electron microscopy. Exposure to 2% sevoflurane for 6 h resulted in BBB ultrastructural abnormalities in the hippocampus of neonatal mice. Sugammadex alone without sevoflurane did not induce apoptosis. The coadministration of sugammadex with sevoflurane to neonatal mice caused a significant increase (150%) in neuroapoptosis in the brain compared with 2% sevoflurane. In neonatal anesthesia, sugammadex could influence neurotoxicity together with sevoflurane. Exposure to 2% sevoflurane for 6 h resulted in BBB ultrastructural abnormalities in the hippocampus of neonatal mice.

Blood–brain barrier disruption caused by neonatal sevoflurane-induced depends on exposure time and is reversible in mice

“…After dehydration, the hippocampal CA1 region was embedded in Epon 812, cut with a microtome, stained with uranyl acetate and lead citrate, and examined using TEM. We observed perivascular spaces because in our previous investigation [3] sevoflurane disrupted the perivascular spaces. We picked 15 capillaries in the hippocampal CA1 region for each animal sampled at each time point.…”

“…Neonatal exposure to anesthetics, such as sevoflurane, induces neuronal apoptosis and results in learning deficits in rodents [1,2]. We showed that exposure to 2% sevoflurane for 6 h resulted in blood–brain barrier (BBB) disruption in the hippocampus of postnatal day 6 (POD6) mice [3]. There are no reports regarding whether neonatal sevoflurane exposure-induced BBB disruption are dependent on exposure time and whether they are reversible.…”

“…Sevoflurane anesthesia was performed as previously described [2,3]. Briefly, POD6 mice were placed in a humid and warm chamber immediately after removal from the maternal cage.…”

“…It should be noted that there are differences between species, duration of anesthesia, and concentration of sevoflurane. Effects of anesthetics on rodents during BGS have been studied by exposing them to the anesthetic for long periods (4–6 h) [1–3]. A shorter period of exposure (30 min) to sevoflurane did not induce obvious long-term effects [5].…”

Corrigendum to “Sugammadex-Enhanced Neuronal Apoptosis following Neonatal Sevoflurane Exposure in Mice”

“…In the article titled “Sugammadex-Enhanced Neuronal Apoptosis following Neonatal Sevoflurane Exposure in Mice” [ 1 ], the concentration of sugammadex injected into the mice, 30 mg/kg, was incorrect; the correct concentration is 300 mg/kg. The undiluted sugammadex concentration was 100 mg/ml and not 10 mg/ml.…”