Prior infection exacerbates postoperative cognitive dysfunction in aged rats

Older patients may experience persisting postoperative cognitive dysfunction (POCD), which is considered to largely depend on surgery-induced (neuro)inflammation. We hypothesize that inflammatory events before surgery could predispose patients to POCD. When part of our aged rats developed Mycoplasma pulmonis, this presented the unique opportunity to investigate whether a pulmonary infection before surgery influences surgery-induced neuroinflammation and POCD. Male 18-mo-old Wistar rats that had recovered from an active mycoplasma infection (infection) and control rats (healthy) were subjected to abdominal surgery and jugular vein catheterization under general anesthesia (surgery) or remained naïve (control). In postoperative week 2, behavioral tests were performed to assess cognitive performance and exploratory behavior. The acute systemic inflammatory response was investigated by measuring plasma IL-6 and IL-12. In the hippocampus, prefrontal cortex and striatum, microglial activity, neurogenesis, and concentrations of IL-6, IL-12, IL1B, and brain-derived neurotropic factor on postoperative day 14 were determined. Rats still showed signs of increased neuroinflammatory activity, as well as cognitive and behavioral changes, 3 wk after the symptoms of infection had subsided. Rats that had experienced infection before surgery exhibited a more generalized and exacerbated postoperative cognitive impairment compared with healthy surgery rats, as well as a prolonged increase in systemic cytokine levels and increased microglial activation in the hippocampus and prefrontal cortex. These findings support the hypothesis that an infection before surgery under general anesthesia exacerbates POCD. Future studies are necessary to determine whether the found effects are aging specific and to investigate the magnitude and time course of this effect in a controlled manner.

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Autophagy attenuates postoperative cognitive dysfunction by up-regulating cystatin C in aged rats undergoing splenectomy

10.21203/rs.2.12725/v3 ◽

2019 ◽

Author(s):

Bi Xing-hua ◽

Zhou Long-yuan ◽

Cai Chang ◽

Qi Yong ◽

Yan Li

Keyword(s):

Learning And Memory ◽

Cognitive Dysfunction ◽

Cystatin C ◽

Postoperative Cognitive Dysfunction ◽

The Other ◽

Inflammatory Factors ◽

Aged Rats ◽

Tnf Α ◽

Neuro Inflammation ◽

Related Proteins

Abstract B ackground : This study aimed to explore whether autophagy can attenuate postoperative cognitive dysfunction (POCD) by up-regulating cystatin C (CysC) in aged rats undergoing splenectomy. Methods : Rats were randomized into four groups ( n = 10 per group): normal control (CON), surgery (SUR), surgery + rapamycin (autophagy inducer) at 1.0 mg/kg/d (RAP), and surgery + 3-methyladenine (autophagy inhibitor) at 3.0 mg/kg/d (3-MA). Treatments were carried out for four weeks. Postoperative learning and memory were assessed using the Morris water maze. Hippocampal expression of the autophagy-related proteins ATG5, LC-3B, Beclin1, and p62 as well as Cys C was assayed using Western blotting and real-time polymerase chain reaction. Results: SUR animals showed higher levels of autophagy and higher expression of autophagy proteins and Cys C than CON animals. These levels were even higher in RAP animals, which also showed lower levels of the inflammatory factors IL-1β, IL-6 and TNF-α than the other groups. Learning and memory functions were higher in RAP animals than in the other groups on days 5 and 7. Effects of 3-MA were opposite to those of RAP. Conclusion : Autophagy improves learning and memory in aged rats following splenectomy, which may involve up-regulation of Cys C and attenuation of neuro-inflammation.

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The Effect of Dexmedetomidine on Cognitive Function and Protein Expression of Aβ, p-Tau, and PSD95 after Extracorporeal Circulation Operation in Aged Rats

BioMed Research International ◽

10.1155/2018/4014021 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Ying Zhang ◽

Yong Lin ◽

Qing Liu ◽

Xuemei Yuan ◽

Anqiong Mao ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Prefrontal Cortex ◽

Cognitive Function ◽

Protein Expression ◽

Cognitive Dysfunction ◽

Extracorporeal Circulation ◽

Postoperative Cognitive Dysfunction ◽

Favorable Outcome ◽

Neurologic Complications ◽

Aged Rats

Postoperative cognitive dysfunction (POCD) is a kind of serious neurologic complications and dexmedetomidine has a certain effect on POCD. However, functional mechanism of dexmedetomidine on POCD still remains unclear, so the research mainly studied the effect of dexmedetomidine on cognitive function and protein expression in hippocampus and prefrontal cortex cerebrospinal fluid after extracorporeal circulation operation in aged rats. We Found that, compared with POCD group, the cognitive function was improved in POCD + Dex group. We speculate that dexmedetomidine could improve the cognitive function after extracorporeal circulation operation in aged rats and Aβ, p-Tau, and PSD95 protein might have contributed to this favorable outcome.

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Autophagy attenuates postoperative cognitive dysfunction by up-regulating cystatin C in aged rats undergoing splenectomy

10.21203/rs.2.12725/v2 ◽

2019 ◽

Author(s):

Bi Xing-hua ◽

Zhou Long-yuan ◽

Cai Chang ◽

Qi Yong ◽

Yan Li

Keyword(s):

Learning And Memory ◽

Cognitive Dysfunction ◽

Cystatin C ◽

Postoperative Cognitive Dysfunction ◽

The Other ◽

Inflammatory Factors ◽

Aged Rats ◽

Tnf Α ◽

Neuro Inflammation ◽

Related Proteins

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Association of apolipoprotein ε4 with postoperative cognitive dysfunction and long-term memory in elderly patients undergoing general anesthesia

10.26226/morressier.57108e2cd462b80290b49d88 ◽

2016 ◽

Author(s):

Livia Valentin

Keyword(s):

Elderly Patients ◽

General Anesthesia ◽

Cognitive Dysfunction ◽

Postoperative Cognitive Dysfunction ◽

Long Term Memory ◽

Term Memory

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Acute pre-operative ibuprofen improves cognition in a rat model for postoperative cognitive dysfunction

Journal of Neuroinflammation ◽

10.1186/s12974-021-02206-y ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Klaske Oberman ◽

Iris Hovens ◽

Jacco de Haan ◽

Joana Falcao-Salles ◽

Barbara van Leeuwen ◽

...

Keyword(s):

Cognitive Dysfunction ◽

Morris Water Maze ◽

Rat Model ◽

Gut Microbiome ◽

Water Maze ◽

Single Injection ◽

Postoperative Cognitive Dysfunction ◽

Aged Rats ◽

Short Term ◽

Term Memory

Abstract Background Inflammation is considered a key factor in the development of postoperative cognitive dysfunction (POCD). Therefore, we hypothesized that pre-operative anti-inflammatory treatment with ibuprofen would inhibit POCD in our rat-model. Methods Male Wistar rats of 3 or 23 months old received a single injection of ibuprofen (15 mg/kg i.p.) or were control handled before abdominal surgery. Timed blood and fecal samples were collected for analyses of inflammation markers and gut microbiome changes. Behavioral testing was performed from 9 to 14 days after surgery, in the open field, novel object- and novel location-recognition tests and Morris water maze. Neuroinflammation and neurogenesis were assessed by immune histochemistry after sacrifice on postoperative day 14. Results Ibuprofen improved short-term spatial memory in the novel location recognition test, and increased hippocampal neurogenesis. However, these effects were associated with increased hippocampal microglia activity. Whereas plasma cytokine levels (IL1-β, IL6, IL10, and TNFα) were not significantly affected, VEGF levels increased and IFABP levels decreased after ibuprofen. Long-term memory in the Morris water maze was not significantly improved by ibuprofen. The gut microbiome was neither significantly affected by surgery nor by ibuprofen treatment. In general, effects in aged rats appeared similar to those in young rats, though less pronounced. Conclusion A single injection of ibuprofen before surgery improved hippocampus-associated short-term memory after surgery and increased neurogenesis. However, this favorable outcome seemed not attributable to inhibition of (neuro)inflammation. Potential contributions of intestinal and blood-brain barrier integrity need further investigation. Although less pronounced compared to young rats, effects in aged rats indicate that even elderly individuals could benefit from ibuprofen treatment.

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Relationship among anesthesia technique, surgical stress, and cognitive dysfunction following spinal surgery: a randomized trial

Journal of Neurosurgery Spine ◽

10.3171/2019.4.spine184 ◽

2019 ◽

Vol 31 (6) ◽

pp. 894-901 ◽

Cited By ~ 2

Author(s):

Anna A. Ezhevskaya ◽

Alexei M. Ovechkin ◽

Zhanna B. Prusakova ◽

Valery I. Zagrekov ◽

Sergey G. Mlyavykh ◽

...

Keyword(s):

Cognitive Function ◽

Pain Management ◽

Epidural Analgesia ◽

General Anesthesia ◽

Cognitive Dysfunction ◽

Postoperative Cognitive Dysfunction ◽

Group 2 ◽

Cellular Immune ◽

Inflammatory Changes ◽

Group 1

OBJECTIVESurgical trauma is known to result in systemic inflammatory changes that can lead to postoperative cognitive dysfunction. In the present study, the authors compared the effects of an epidural anesthesia protocol to those of traditional anesthesia with regard to postoperative inflammatory changes, cellular immunity, and cognitive dysfunction.METHODSForty-eight patients, ages 45–60 years, underwent multilevel thoracolumbar decompression and fusion and were randomly assigned to one of two groups: group 1 (27 patients) had combined epidural and general anesthesia, followed by epidural analgesia for 48 hours after surgery, and group 2 (21 patients) had general anesthesia, followed by traditional opioid pain management after surgery. At multiple time points, data on pain control, cognitive function, cellular immunity, and inflammatory markers were collected.RESULTSGroup 1 patients demonstrated lower pain levels, less systemic inflammation, less cellular immune dysfunction, and less postoperative cognitive dysfunction than group 2 patients.CONCLUSIONSThe use of combined epidural and general anesthesia followed by postoperative epidural analgesia during the first 48 hours after multilevel thoracolumbar decompression and fusion surgery had a significant positive effect on pain management, cellular immune function, systemic inflammation, and postoperative cognitive function.Clinical trial registration no.: 115080510080 (http://rosrid.ru)

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Transcutaneous electrical acupoint stimulation for postoperative cognitive dysfunction in geriatric patients with gastrointestinal tumor: a randomized controlled trial

Trials ◽

10.1186/s13063-021-05534-9 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Lijuan Xi ◽

Fang Fang ◽

Haijuan Yuan ◽

Daorong Wang

Keyword(s):

General Anesthesia ◽

Cognitive Dysfunction ◽

Geriatric Patients ◽

Postoperative Cognitive Dysfunction ◽

Radical Resection ◽

Gastrointestinal Tumors ◽

Gastrointestinal Tumor ◽

The Third ◽

Link Type ◽

Acupoint Stimulation

Abstract Background This study aimed to evaluate the effect of perioperative transcutaneous electrical acupoint stimulation (TEAS) on postoperative cognitive dysfunction (POCD) in older patients who were diagnosed with gastrointestinal tumor and received radical resection of gastrointestinal tumors under general anesthesia. Methods A total of 68 patients who received radical resection of gastrointestinal tumors under general anesthesia were randomly divided into two groups. TEAS group patients received TEAS treatment. The treatment time was 30 min before the induction of anesthesia until the end of the surgery, 1 day before operation and from the first day to the third day after the operation. Except on the day of surgery, we treated the patients for 30 min once a day. In the sham TEAS group, the electronic stimulation was not applied and the treatment was the same as the TEAS group. The primary outcome was perioperative cognition evaluated by the Mini-Mental State Examination (MMSE) and secondary outcomes were the perioperative level of interleukin-6 (IL-6), S100 calcium-binding protein β (S100β), and C-reactive protein (CRP). Results The postoperative score of MMSE, orientation, memory, and short-term recall in the sham TEAS group was significantly lower than the preoperative and TEAS group (P < 0.05). The incidence of POCD in the TEAS group (21.88%) was lower than those in the sham TEAS group (40.63%). S100β, IL-6, and CRP in the TEAS group were significantly lower than those in the sham TEAS group on the third day after the operation (P< 0.05). Postoperative S100β, IL-6, and CRP in two groups were significantly higher than those before operation except for S100β on the third day after the operation in the TEAS group (P < 0.05). Conclusions Perioperative TEAS treatment reduced the postoperative inflammatory response and increased the postoperative cognitive function score and decrease the incidence of POCD in geriatric patients with gastrointestinal tumor. Trial registration ClinicalTrials.gov NCT04606888. Registered on 27 October 2020. https://register.clinicaltrials.gov.

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Incidence of Postoperative Cognitive Dysfunction Following Inhalational Vs. Total Intravenous General Anesthesia: A Systematic Review and Meta-Analysis.

10.21203/rs.3.rs-1211887/v1 ◽

2022 ◽

Author(s):

Daniel Negrini ◽

Andrew Wu ◽

Atsushi Oba ◽

Ben Harnke ◽

Nicholas Ciancio ◽

...

Keyword(s):

Systematic Review ◽

General Anesthesia ◽

Cognitive Dysfunction ◽

Meta Analysis ◽

Postoperative Cognitive Dysfunction ◽

Primary Objective ◽

Intravenous Anesthesia ◽

Robust Designs ◽

Secondary Objective ◽

Intravenous General Anesthesia

Abstract Postoperative cognitive dysfunction (POCD) has been increasingly recognized as a contributor to postoperative complications. A consensus-working group recommended that POCD should be distinguished between delayed cognitive recovery, i.e., evaluations up to 30 days postoperative, and neurocognitive disorder, i.e., assessments performed between 30 days and 12 months after surgery. Additionally, the choice of the anesthetic, either inhalational or total intravenous anesthesia (TIVA) and its effect on the incidence of POCD, has become a focus of research. Our primary objective was to search the literature and conduct a meta-analysis to verify whether the choice of general anesthesia may impact the incidence of POCD in the first 30 days postoperatively. As a secondary objective, a systematic review of the literature was conducted to estimate the effects of the anesthetic on POCD between 30 days and 12 months postoperative. For the primary objective, an initial review of 1,913 articles yielded 12 studies with a total of 3,639 individuals. For the secondary objective, five studies with a total of 751 patients were selected. In the first 30 days postoperative, the odds-ratio for POCD in TIVA group was 0.60 (95% CI = 0.40 - 0.91; p = 0.02), compared to the inhalational group. TIVA was associated with a lower incidence of POCD in the first 30 days postoperatively. Regarding the secondary objective, due to the small number of selected articles and its high heterogeneity, a metanalysis was not conducted. Giving the heterogeneity of criteria for POCD, future prospective studies with more robust designs should be performed to fully address this question.

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