Isoflurane anesthesia results in reversible ultrastructure and occludin tight junction protein expression changes in hippocampal blood–brain barrier in aged rats

Cao, Yanyan; Ni, Cheng; Li, Zhengqian; Li, Lunxu; Liu, Huan; Wang, Chunyi; Zhong, Yan; Cui, Dehua; Guo, Xiangyang

doi:10.1016/j.neulet.2014.12.018

Cited by 48 publications

(52 citation statements)

References 24 publications

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“…Volatile anesthetics can influence BBB opening and integrity in aged rats [10, 11]. In this study, we confirmed disruption of the BBB ultrastructure in neonatal mice exposed to sevoflurane.…”

Section: Discussionsupporting

confidence: 79%

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Sugammadex-Enhanced Neuronal Apoptosis following Neonatal Sevoflurane Exposure in Mice

Satomoto

Sun

Adachi

et al. 2016

Anesthesiology Research and Practice

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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.

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Section: Discussionsupporting

confidence: 79%

“…Volatile anesthetics can influence BBB opening and integrity in aged rats [10, 11] and in brain injury [12]. Volatile anesthetics at clinical concentrations induced neuronal apoptosis and cognitive disorders in neonatal and aged rodents [13–19].…”

Section: Introductionmentioning

confidence: 99%

Sugammadex-Enhanced Neuronal Apoptosis following Neonatal Sevoflurane Exposure in Mice

Satomoto

Sun

Adachi

et al. 2016

Anesthesiology Research and Practice

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“…Because of these characteristics, FL has been used extensively as an in vivo marker to determine the changes in the paracellular permeability of BBB in different diseases (Kaya and Ahishali, 2011). In most experiments, investigators use the absolute brain concentrations of FL as a measure of BBB permeability (Cao et al, 2015;Nishioku et al, 2010;Oppenheim et al, 2013;Tress et al, 2014). However, this approach may result in inaccuracies if the systemic exposure of the marker, such as area under the plasma concentrationtime curve (AUC), is also altered by the disease or the intervention.…”

mentioning

confidence: 99%

Effects of Pringle maneuver and partial hepatectomy on the pharmacokinetics and blood–brain barrier permeability of sodium fluorescein in rats

et al. 2015

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Liver diseases are known to affect the function of remote organs. The aim of the present study was to investigate the effects of Pringle maneuver, which results in hepatic ischemia-reperfusion (IR) injury, and partial hepatectomy (Hx) on the pharmacokinetics and brain distribution of sodium fluorescein (FL), which is a widely used marker of blood-brain barrier (BBB) permeability. Rats were subjected to Pringle maneuver (total hepatic ischemia) for 20 min with (HxIR) or without (IR) 70% hepatectomy. Sham-operated animals underwent laparotomy only. After 15 min or 8h of reperfusion, a single 25-mg/kg dose of FL was injected intravenously and serial (0-30 min) blood and bile and terminal brain samples were collected. Total and free (ultrafiltration) plasma, total brain homogenate, and bile concentrations of FL and/or its glucuronidated metabolite (FL-Glu) were determined by HPLC. Both IR and HxIR caused significant reductions in the biliary excretions of FL and FL-Glu, resulting in significant increases in the plasma AUC of the marker. Additionally, the free fraction of FL in plasma was significantly increased by HxIR. Although the brain concentrations of FL were increased by almost twofold in both IR and HxIR animals, the brain concentrations corrected by the free FL AUC (and not the total AUC) were similar in both groups at either time points. It is concluded that Pringle maneuver and/or partial hepatectomy substantially alters the hepatobiliary disposition, plasma AUC, plasma free fraction, and brain accumulation of FL without altering the BBB permeability to the marker.

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“…Isoflurane anesthesia in cats alters blood brain permeability in a dose dependent manner, resulting in increased cerebral brain volumes (Tetrault et al, 2008). Similar studies in rats exposed to isoflurane produced BBB dysfunction with decreased levels of the tight junction protein occludin (Cao et al, 2015). Taken together, these studies provide evidence that BBB dysfunction may also contribute to anesthesia-induced neurotoxicity.…”

Section: Blood Brain Barrier and Cerebrovasculaturementioning

confidence: 82%

“…This barrier controls the flow of chemicals between the CSF and brain. Prior studies have demonstrated that isoflurane exposure in adult rats down regulates expression of occludin with resulting impairment in tight junction function (Cao et al, 2015). This raises the question of whether exposure to anesthesia during early development has negative implications for maintaining the CSF/brain parenchymal barrier.…”

Section: Gliogenesismentioning

confidence: 99%

A holistic approach to anesthesia-induced neurotoxicity and its implications for future mechanistic studies

Zanghi

Jevtović-Todorović

2017

Neurotoxicology and Teratology

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The year 2016 marked the 15th anniversary since anesthesia-induced developmental neurotoxicity and its resulting cognitive dysfunction were first described. Since that time, multiple scientific studies have supported these original findings and investigated possible mechanisms behind anesthesia-induced neurotoxicity. This paper reviews the existing mechanistic literature on anesthesia-induced neurotoxicity in the context of a holistic approach that emphasizes the importance of both neuronal and non-neuronal cells during early postnatal development. Sections are divided into key stages in early neural development; apoptosis, neurogenesis, migration, differentiation, synaptogenesis, gliogenesis, myelination and blood brain barrier/cerebrovasculature. In addition, the authors combine the established literature in the field of anesthesia-induced neurotoxicity with literature from other related scientific fields to speculate on the potential role of non-neuronal cells and to generate new future hypotheses for understanding anesthetic toxicity and its application to the practice of pediatric anesthesia.

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Isoflurane anesthesia results in reversible ultrastructure and occludin tight junction protein expression changes in hippocampal blood–brain barrier in aged rats

Cited by 48 publications

References 24 publications

Sugammadex-Enhanced Neuronal Apoptosis following Neonatal Sevoflurane Exposure in Mice

Sugammadex-Enhanced Neuronal Apoptosis following Neonatal Sevoflurane Exposure in Mice

Effects of Pringle maneuver and partial hepatectomy on the pharmacokinetics and blood–brain barrier permeability of sodium fluorescein in rats

A holistic approach to anesthesia-induced neurotoxicity and its implications for future mechanistic studies

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