Single and repeated exposures to the volatile anesthetic isoflurane do not impair operant performance in aged rats

Walters, Jennifer L.; Chelonis, John J.; Fogle, Charles M.; Orser, Beverley A.; Paule, Merle G.

doi:10.1016/j.neuro.2016.07.012

Cited by 7 publications

(4 citation statements)

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“…We observed that LPS, but not ISO, increased the expression of HDAC2 in the hippocampus in adult mice. Previous studies demonstrated that cognitive impairment is highly related to HDAC2, and repeated exposure to ISO in aged rats upregulated HDAC2 expression [71]. Maternal exposure to isoflurane impaired learning and memory of the offspring and increased HDAC mRNA [72].…”

Section: Discussionmentioning

confidence: 99%

HDAC2 hyperexpression alters hippocampal neuronal transcription and microglial activity in neuroinflammation-induced cognitive dysfunction

Sun

Teng

Yang

et al. 2019

J Neuroinflammation

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BackgroundInflammation can induce cognitive dysfunction in patients who undergo surgery. Previous studies have demonstrated that both acute peripheral inflammation and anaesthetic insults, especially isoflurane (ISO), are risk factors for memory impairment. Few studies are currently investigating the role of ISO under acute peri-inflammatory conditions, and it is difficult to predict whether ISO can aggravate inflammation-induced cognitive deficits. HDACs, which are essential for learning, participate in the deacetylation of lysine residues and the regulation of gene transcription. However, the cell-specific mechanism of HDACs in inflammation-induced cognitive impairment remains unknown.MethodsThree-month-old C57BL/6 mice were treated with single versus combined exposure to LPS injected intraperitoneally (i.p.) to simulate acute abdominal inflammation and isoflurane to investigate the role of anaesthesia and acute peripheral inflammation in cognitive impairment. Behavioural tests, Western blotting, ELISA, immunofluorescence, qRT-PCR, and ChIP assays were performed to detect memory, the expressions of inflammatory cytokines, HDAC2, BDNF, c-Fos, acetyl-H3, microglial activity, Bdnf mRNA, c-fos mRNA, and Bdnf and c-fos transcription in the hippocampus.ResultsLPS, but not isoflurane, induced neuroinflammation-induced memory impairment and reduced histone acetylation by upregulating histone deacetylase 2 (HDAC2) in dorsal hippocampal CaMKII+ neurons. The hyperexpression of HDAC2 in neurons was mediated by the activation of microglia. The decreased level of histone acetylation suppressed the transcription of Bdnf and c-fos and the expressions of BDNF and c-Fos, which subsequently impaired memory. The adeno-associated virus ShHdac2, which suppresses Hdac2 after injection into the dorsal hippocampus, reversed microglial activation, hippocampal glutamatergic BDNF and c-Fos expressions, and memory deficits.ConclusionsReversing HDAC2 in hippocampal CaMKII+ neurons exert a neuroprotective effect against neuroinflammation-induced memory deficits.

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Section: Discussionmentioning

confidence: 99%

HDAC2 hyperexpression alters hippocampal neuronal transcription and microglial activity in neuroinflammation-induced cognitive dysfunction

Sun

Teng

Yang

et al. 2019

J Neuroinflammation

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“…The tertiary dentate matrix appears on day E22 and is replaced by SGZ between days P20 and P30 (Altman & Bayer, 1990). While many studies found isoflurane exposure to rats during infantile period caused delayed‐onset hippocampal‐dependent cognitive deficits (Chinn et al., 2019; Stratmann et al., 2009; Wang, Lu, et al., 2018; Wang et al., 2016; Zhu et al., 2010), the impairment of cognitive functions was not demonstrated following isoflurane exposure to adult animals (Altman & Bayer, 1990; Stratmann, Sall, Bell, et al., 2010; Walters et al., 2016; Zhu et al., 2010). Our finding that isoflurane exposure has neurotoxic effect on nascent and mature neurons derived from tertiary dentate matrix may, in part explain, the cognitive impairment resulting from isoflurane exposure to the young brain.…”

Section: Discussionmentioning

confidence: 99%

The neurotoxic effect of isoflurane on age‐defined neurons generated from tertiary dentate matrix in mice

Xiao

Zhang

et al. 2020

Brain and Behavior

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“…Similarly, repeated exposure to 5 h of isoflurane (end-tidal isoflurane = 0.7–1.5 vol %) in infant Rhesus macaque monkeys exposed on postnatal day (P)6, P9, and P12 resulted in evidence of motor and socioemotional deficits when tested 12 months later; infants that were only exposed once on P5 had no such alterations (134). In older mice, isoflurane alone has been associated with hippocampal inflammation and impairment of spatial memory (135), however in rats, isoflurane alone did not have an effect on spatial memory processes, even with repeat anesthetics (136). In contrast, in the setting of myocardial ischemia-reperfusion injury in rats, sevoflurane seems to exert a protective effect, mitigating impairments in long-term potentiation (LTP) and improving memory function (137, 138).…”

Section: Etiology Of Pocdmentioning

confidence: 99%

The Role of Neuroinflammation in Postoperative Cognitive Dysfunction: Moving From Hypothesis to Treatment

2019

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Postoperative cognitive dysfunction (POCD) is a common complication of the surgical experience and is common in the elderly and patients with preexisting neurocognitive disorders. Animal and human studies suggest that neuroinflammation from either surgery or anesthesia is a major contributor to the development of POCD. Moreover, a large and growing body of literature has focused on identifying potential risk factors for the development of POCD, as well as identifying candidate treatments based on the neuroinflammatory hypothesis. However, variability in animal models and clinical cohorts makes it difficult to interpret the results of such studies, and represents a barrier for the development of treatment options for POCD. Here, we present a broad topical review of the literature supporting the role of neuroinflammation in POCD. We provide an overview of the cellular and molecular mechanisms underlying the pathogenesis of POCD from pre-clinical and human studies. We offer a brief discussion of the ongoing debate on the root cause of POCD. We conclude with a list of current and hypothesized treatments for POCD, with a focus on recent and current human randomized clinical trials.

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Single and repeated exposures to the volatile anesthetic isoflurane do not impair operant performance in aged rats

Cited by 7 publications

References 84 publications

HDAC2 hyperexpression alters hippocampal neuronal transcription and microglial activity in neuroinflammation-induced cognitive dysfunction

HDAC2 hyperexpression alters hippocampal neuronal transcription and microglial activity in neuroinflammation-induced cognitive dysfunction

The neurotoxic effect of isoflurane on age‐defined neurons generated from tertiary dentate matrix in mice

The Role of Neuroinflammation in Postoperative Cognitive Dysfunction: Moving From Hypothesis to Treatment

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