Impaired Spatial Learning Memory after Isoflurane Anesthesia or Appendectomy in Aged Mice is Associated with Microglia Activation

Wang, Huilin; Ma, Ru; Fang, Hao; Zhao, Xue; Liao, Qingwu

doi:10.4137/jcd.s30596

Cited by 47 publications

(35 citation statements)

References 58 publications

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“…CNS inflammation is one of the main causes of POCD, and over-activation of microglia might be an important link leading to CNS inflammation. 16 Several studies have shown that microglia hyper-activation can be stained with immunohistochemistry and labeled with iba1. 17 In this experiment, microscopic observation revealed that the number of iba1-labeled activated microglia in laparotomy group was remarkably increased than that of the sham control group.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine reduces hippocampal microglia inflammatory response induced by surgical injury through inhibiting NLRP3

Zhang

Zheng

et al. 2019

Chinese Journal of Traumatology

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Purpose To investigate whether dexmedetomidine (Dex) can reduce the production of inflammatory factor IL-1β by inhibiting the activation of NLRP3 inflammasome in hippocampal microglia, thereby alleviating the inflammatory response of the central nervous system induced by surgical injury. Methods Exploratory laparotomy was used in experimental models in this study. Totally 48 Sprague Dawley male rats were randomly divided into 4 groups ( n = 12 for each), respectively sham control (group A), laparotomy only (group B); and Dex treatment with different doses of 5 μg/kg (group D1) or 10 μg/kg (group D2). Rats in groups D1 and D2 were intraperitoneally injected with corresponding doses of Dex every 6 h. The rats were sacrificed 12 h after operation; the hippocampus tissues were isolated, and frozen sections were made. The microglia activation was estimated by immunohistochemistry. The protein expression of NLRP3, caspase-1, ASC and IL-1β were detected by immunoblotting. All data were presented as mean ± standard deviation, and independent sample t test was used to analyze the statistical difference between groups. Results The activated microglia in the hippocampus of the rats significantly increased after laparotomy (group B vs. sham control, p < 0.01). After Dex treatment, the number was decreased in a dose-dependent way (group D1 vs. D2, p < 0.05), however the activated microglia in both groups were still higher than that of sham controls (both p < 0.05). Further Western blot analysis showed that the protein expression levels of NLRP3, caspase-1, ASC and downstream cytokine IL-1β in the hippocampus from the laparotomy group were significantly higher than those of the sham control group (all p < 0.01). The elevated expression of these proteins was relieved after Dex treatment, also in a dose-dependent way (D2 vs. D1 group, p < 0.05). Conclusion Dex can inhibit the activation of microglia and NLRP3 inflammasome in the hippocampus of rats after operation, and the synthesis and secretion of IL-1β are also reduced in a dose-dependent manner by using Dex. Hence, Dex can alleviate inflammation activation on the central nervous system induced by surgical injury.

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Section: Discussionmentioning

confidence: 99%

Dexmedetomidine reduces hippocampal microglia inflammatory response induced by surgical injury through inhibiting NLRP3

Zhang

Zheng

et al. 2019

Chinese Journal of Traumatology

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“…Although anesthesia can result in negative effects during development, such as apoptotic neurodegeneration, deficits in hippocampal synaptic functions, and persistent behavioral and cognitive impairments (Jevtovic‐Todorovic et al, ; Jevtovic‐Todorovic, Boscolo, Sanchez, & Lunardi, ; Loepke et al, ), few studies have investigated neural and behavioral deficits that may extend into adulthood (Cao et al, ; Li, Li, et al, ; Mawhinney et al, ; Wang, Ma, Fang, Xue, & Liao, ). Mature brains may have a distinctive pathophysiological response to isoflurane compared to younger, developing brains, with differences observed in neurogenesis, neuronal differentiation, and cognitive outcomes after anesthesia (Stratmann et al, ; Zhu et al, ).…”

Section: Introductionmentioning

confidence: 99%

Repeated isoflurane in adult male mice leads to acute and persistent motor decrements with long‐term modifications in corpus callosum microstructural integrity

Bajwa

Lee

Halavi

et al. 2018

J of Neuroscience Research

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Isoflurane is a commonly used inhalational anesthetic, clinically and in animal experimental studies. Although it has been reported as safe, recent findings suggest that despite widespread use, isoflurane‐induced inhalational anesthesia can lead to various pathophysiological and cognitive alterations. Therefore, we aimed to investigate the long‐term behavioral and white matter consequences of repeated isoflurane exposure. Twenty 3‐month‐old C57BL/6J male mice received one exposure of isoflurane for 40 min or 2 exposures to isoflurane separated by 3 days. Behavioral paradigms (open field, balance beam, foot fault, rotarod, elevated zero maze, tail suspension, water maze, and social recognition tests) were administered at 1, 3, 5, 7, and 90 days post exposure. Animals exposed to repeated isoflurane showed significant motor deficits on the balance beam and increased anxiety‐like behavior. Animals exposed to single isoflurane showed impaired performance on the foot fault test. Diffusion tensor imaging showed that repeated isoflurane exposure led to long‐term disruption of water diffusivity in corpus callosum (CC) white matter. Furthermore, 2‐D structure‐tensor analysis from stained brain sections showed differences in the microstructural organization of CC white matter in mice with single versus repeated isoflurane exposures. These results suggest that behavioral deficits observed up to 90 days after repeated isoflurane exposure resulted from, at least in part, altered CC white matter microstructural integrity.

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“…Ma et al [22] demonstrated that TNF- α , IL-1 β , IL-4, and IL-6 in the hippocampus increased after surgery and the TNF- α receptor antagonist attenuated the elevation of these cytokines. Wang et al [23] found that the hippocampal IL-1 β , TNF- α , and IFN- γ were overexpressed after surgery in aged mice. Hovens et al [24] demonstrated that the hippocampal IL-6, IL-12, and IL1 β increased after surgery in aged rats.…”

Section: Discussionmentioning

confidence: 99%

Neuroinflammation Induced by Surgery Does Not Impair the Reference Memory of Young Adult Mice

Zhao

Huang

et al. 2016

Mediators of Inflammation

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Postoperative cognitive dysfunction (POCD) increases morbidity and mortality after surgery. But the underlying mechanism is not clear yet. While age is now accepted as the top one risk factor for POCD, results from studies investigating postoperative cognitive functions in adults have been controversial, and data about the very young adult individuals are lacking. The present study investigated the spatial reference memory, IL-1β, IL-6, and microglia activation changes in the hippocampus in 2-month-old mice after anesthesia and surgery. We found that hippocampal IL-1β and IL-6 increased at 6 hours after surgery. Microglia were profoundly activated in the hippocampus 6 to 24 hours after surgery. However, no significant behavior changes were found in these mice. These results indicate that although anesthesia and surgery led to neuroinflammation, the latter was insufficient to impair the spatial reference memory of young adult mice.

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Impaired Spatial Learning Memory after Isoflurane Anesthesia or Appendectomy in Aged Mice is Associated with Microglia Activation

Cited by 47 publications

References 58 publications

Dexmedetomidine reduces hippocampal microglia inflammatory response induced by surgical injury through inhibiting NLRP3

Dexmedetomidine reduces hippocampal microglia inflammatory response induced by surgical injury through inhibiting NLRP3

Repeated isoflurane in adult male mice leads to acute and persistent motor decrements with long‐term modifications in corpus callosum microstructural integrity

Neuroinflammation Induced by Surgery Does Not Impair the Reference Memory of Young Adult Mice

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