Contribution of Metabolic Imaging in the Exploration of Cognitive Disorders Related to COVID-19

On March 11, 2019, the WHO declared COVID-19 a pandemic disease. It is a respiratory tropism SARS COV 2 infection. In the emergency of the pandemic, in medical imaging, only computed tomography (CT) of the lungs was favored to assess lung lesions. In addition, many cases of post-COVID-19 cognitive disorders have been reported. As the curve dips and services restart correctly, other imaging techniques have been used to better explore the disease. The objective of this presentation is to illustrate the contribution of metabolic imaging in the exploration of post COVID-19 cognitive disorders and to discuss the pathophysiological mechanisms. Hypometabolism brain lesions are objective signs of functional impairment whose pathophysiological mechanism is not yet fully understood. Metabolic imaging with PET-SCAN is a suitable tool for exploring these disorders, both for the severity and extent of the lesions and for the topography of the brain damage.

Cognitive Disorders, Depression and Anxiety in Temporal Lobe Epilepsy: An Overview

Partial epilepsies, originating in a specific brain region, affect about 60% of adults with epilepsy. Temporal lobe epilepsy (TLE) is the most prevalent subtype within this category, often necessitating surgical intervention due to its refractoriness to antiepileptic drugs (AEDs). Hippocampal sclerosis, a common underlying pathology, often exacerbates the severity by introducing cognitive and emotional challenges. This review delves deeper into the cognitive profile of TLE, along with the risk factors for cognitive disorders, depression, and anxiety in this population.

Description of Post-Stroke Cognitive Disorders at Abidjan University Hospitals, Côte d’Ivoire

Stroke patients often experience motor deficits and cognitive problems after a stroke. Objective: To improve our understanding of the cognitive consequences of stroke. Method: a descriptive and analytical cross-sectional study was conducted over 12-month period in the neurology departments of the Cocody and Treichville Hospitals in Côte d’Ivoire. Results: Out of 724 patients admitted to the neurology department, 415 (57.32%) were stroke patients, of which 145 (34.94%) were screened. The frequency of global cognitive functioning impairment was 86.21%, significantly higher than the frequency of patients without impairment, which was 13.79%. The study focused on detailing the cognitive status of stroke patients in neurology departments, assessing several cognitive functions during the subacute phase of stroke. These functions included global cognitive functioning, executive functions, language and memory. The frequency of post-stroke cognitive impairment is high among stroke patients in Abidjan. This frequency is comparable to figures found in Subsaharian stroke populations. Demographic and clinical characteristics studied included age, gender, education level, employment status, vascular diseases and cerebral affected area. Among these characteristics, only the education level and the cerebral affected area have been found significant. Conclusion: The incidence of cognitive impairment after a stroke is significantly high among stroke patients in Abidjan.

Anesthesia,Anesthetics,and Postoperative Cognitive Dysfunction in Elderly Patients

Postoperative cognitive dysfunction(POCD)remains a major issue that worsens the prognosis of elderly surgery patients.This article reviews the current research on the effect of different anesthesia methods and commonly utilized anesthetics on the incidence of POCD in elderly patients,aiming to provide an understanding of the underlying mechanisms contributing to this condition and facilitate the development of more reasonable anesthesia protocols,ultimately reducing the incidence of POCD in elderly surgery patients.

Recombinant chitinase-3-like protein 1 alleviates learning and memory impairments via M2 microglia polarization in postoperative cognitive dysfunction mice

Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.

Correlation of preoperative inflammatory factors and emotional disorders with postoperative delirium in patients with craniocerebral trauma

BACKGROUND Traumatic brain injury(TBI)imposes a substantial societal and familial burden due to its high disability and fatality rates,rendering it a serious public health problem.Some patients with TBI have poor treatment outcomes and are prone to postoperative delirium(POD),which affects their quality of life.Anxiety has been linked to increased POD incidence in some studies,while others have found no correlation.AIM To investigate the correlation of POD risk factors,preoperative inflammatory factors,and mood disorders in patients with TBI.METHODS We retrospectively collected data on the treatment of 80 patients with TBI from November 2021 to September 2023.Patients were grouped as POD and non-POD,according to their POD status,and the general data of the two groups were compared.Inflammatory factor levels were detected preoperatively,and the Hamilton Depression Scale(HAMD)and Hamilton Anxiety Scale(HAMA)were used to investigate the risk factors associated with POD in these patients.Logistic regression was used to identify the independent risk factors.RESULTS Twenty-one patients(26.25%)developed POD,including 7,10,and 4 cases of the excitatory,inhibitory,and mixed types,respectively.There were 59 cases(73.75%)in the non-POD group.Compared with the non-POD group,the POD group had a significantly higher proportion of patients with low Glasgow Coma Scale(GCS)scores before admission,unilateral mydriasis,preoperative hemorrhagic shock,intraventricular hemorrhage(IVH),and postoperative hyperglycemic hyperosmolar disease(P<0.05).In the POD group,interleukin-6(IL-6),human tumor necrosis factor-α(TNF-α),myeloperoxidase levels,HAMA,and HAMD scores were higher than those in the non-POD group(all P<0.05).Logistic multivariate analysis showed that GCS score at admission,IVH,IL-6,TNF-α,HAMA,and HAMD were independent risk factors for POD in patients with TBI(P<0.05).CONCLUSION Low GCS score at admission,IVH,elevated IL-6 and TNF-α,other inflammatory indicators,anxiety,and depression,can increase the risk of POD in patients with TBI after surgery.

Impact of thoracic paravertebral block and sufentanil on outcomes and postoperative cognitive dysfunction in thoracoscopic lung cancer surgery

BACKGROUND Postoperative pain management and cognitive function preservation are crucial for patients undergoing thoracoscopic surgery for lung cancer(LC).This is achieved using either a thoracic paravertebral block(TPVB)or sufentanil(SUF)-based multimodal analgesia.However,the efficacy and impact of their combined use on postoperative pain and postoperative cognitive dysfunction(POCD)remain unclear.AIM To explore the analgesic effect and the influence on POCD of TPVB combined with SUF-based multimodal analgesia in patients undergoing thoracoscopic radical resection for LC to help optimize postoperative pain management and improve patient outcomes.METHODS This retrospective analysis included 107 patients undergoing thoracoscopic radical resection for LC at The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital between May 2021 and January 2023.Patients receiving SUF-based multimodal analgesia(n=50)and patients receiving TPVB+SUF-based multimodal analgesia(n=57)were assigned to the control group and TPVB group,respectively.We compared the Ramsay Sedation Scale and visual analog scale(VAS)scores at rest and with cough between the two groups at 2,12,and 24 h after surgery.Serum levels of epinephrine(E),angio-tensin Ⅱ(Ang Ⅱ),norepinephrine(NE),superoxide dismutase(SOD),vascular endothelial growth factor(VEGF),transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),and S-100 calcium-binding proteinβ(S-100β)were measured before and 24 h after surgery.The Mini-Mental State Examination(MMSE)was administered 1 day before surgery and at 3 and 5 days after surgery,and the occurrence of POCD was monitored for 5 days after surgery.Adverse reactions were also recorded.RESULTS There were no significant time point,between-group,and interaction effects in Ramsay sedation scores between the two groups(P>0.05).Significantly,there were notable time point effects,between-group differences,and interaction effects observed in VAS scores both at rest and with cough(P<0.05).The VAS scores at rest and with cough at 12 and 24 h after surgery were lower than those at 2 h after surgery and gradually decreased as postoperative time increased(P<0.05).The TPVB group had lower VAS scores than the control group at 2,12,and 24 h after surgery(P<0.05).The MMSE scores at postoperative days 1 and 3 were markedly higher in the TPVB group than in the control group(P<0.05).The incidence of POCD was significantly lower in the TPVB group than in the control group within 5 days after surgery(P<0.05).Both groups had elevated serum E,Ang Ⅱ,and NE and decreased serum SOD levels at 24 h after surgery compared with the preoperative levels,with better indices in the TPVB group(P<0.05).Marked elevations in serum levels of VEGF,TGF-β1,TNF-α,and S-100β were observed in both groups at 24 h after surgery,with lower levels in the TPVB group than in the control group(P<0.05).CONCLUSION TPVB combined with SUF-based multimodal analgesia further relieves pain in patients undergoing thoracoscopic radical surgery for LC,enhances analgesic effects,reduces postoperative stress response,and inhibits postoperative increases in serum VEGF,TGF-β1,TNF-α,and S-100β levels.This scheme also reduced POCD and had a high safety profile.

Small extracellular vesicles secreted by induced pluripotent stem cell-derived mesenchymal stem cells improve postoperative cognitive dysfunction in mice with diabetes

Postoperative cognitive dysfunction(POCD)is a common surgical complication.Diabetes mellitus(DM)increases risk of developing POCD after surgery.DM patients with POCD seriously threaten the quality of patients’life,however,the intrinsic mechanism is unclear,and the effective treatment is deficiency.Previous studies have demonstrated neuronal loss and reduced neurogenesis in the hippocampus in mouse models of POCD.In this study,we constructed a mouse model of DM by intraperitoneal injection of streptozotocin,and then induced postoperative cognitive dysfunction by transient bilateral common carotid artery occlusion.We found that mouse models of DM-POCD exhibited the most serious cognitive impairment,as well as the most hippocampal neural stem cells(H-NSCs)loss and neurogenesis decline.Subsequently,we hypothesized that small extracellular vesicles secreted by induced pluripotent stem cell-derived mesenchymal stem cells(iMSC-sEVs)might promote neurogenesis and restore cognitive function in patients with DM-POCD.iMSC-sEVs were administered via the tail vein beginning on day 2 after surgery,and then once every 3 days for 1 month thereafter.Our results showed that iMSC-sEVs treatment significantly recovered compromised proliferation and neuronal-differentiation capacity in H-NSCs,and reversed cognitive impairment in mouse models of DM-POCD.Furthermore,miRNA sequencing and qPCR showed miR-21-5p and miR-486-5p were the highest expression in iMSC-sEVs.We found iMSC-sEVs mainly transferred miR-21-5p and miR-486-5p to promote H-NSCs proliferation and neurogenesis.As miR-21-5p was demonstrated to directly targete Epha4 and CDKN2C,while miR-486-5p can inhibit FoxO1 in NSCs.We then demonstrated iMSC-sEVs can transfer miR-21-5p and miR-486-5p to inhibit EphA4,CDKN2C,and FoxO1 expression in H-NSCs.Collectively,these results indicate significant H-NSC loss and neurogenesis reduction lead to DM-POCD,the application of iMSC-sEVs may represent a novel cell-free therapeutic tool for diabetic patients with postoperative cognitive dysfunction.

Effects of surgical treatment modalities on postoperative cognitive function and delirium in elderly patients with extremely unstable hip fractures

BACKGROUND As the perioperative risk of elderly patients with extremely unstable hip fractures(EUHFs)is relatively high and therapeutic effect is not satisfactory,new therapeutic strategies need to be proposed urgently to improve the efficacy and clinical outcomes of such patients.AIM To determine the influence of two surgical treatment modalities on postoperative cognitive function(CF)and delirium in elderly patients with EUHFs.METHODS A total of 60 elderly patients consecutively diagnosed with EUHF between September 2020 and January 2022 in the Chongqing University Three Gorges Hospital were included.Of them,30 patients received conventional treatment(control group;general consultation+fracture type-guided internal fixation),and the other 30 received novel treatment(research group;perioperative multidisciplinary treatment diagnosis and treatment+individualized surgical plan+risk prediction).Information on hip function[Harris hip score(HHS)],perioperative risk of orthopedic surgery[Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity(POSSUM)],CF[Montreal cognitive assessment scale(MoCA)],postoperative delirium[mini-cognitive(Mini-Cog)],adverse events(AEs;internal fixation failure,infection,nonunion,malunion,and postoperative delirium),and clinical indicators[operation time(OT),postoperative hospital length of stay(HLOS),ambulation time,and intraoperative blood loss(IBL)]were collected from both groups for comparative analyses.RESULTS The HHS scores were similar between both groups.The POSSUM score at 6 mo after surgery was significantly lower in the research group compared with the control group,and MoCA and Mini-Cog scores were statistically higher.In addition,the overall postoperative complication rate was significantly lower in the research than in the control group,including reduced OT,postoperative HLOS,ambulation time,and IBL.CONCLUSION The new treatment modality has more clinical advantages over the conventional treatment,such as less IBL,faster functional recovery,more effectively optimized perioperative quality control,improved postoperative CF,mitigated postoperative delirium,and reduced operation-related AEs.

Development and validation of a screening instrument for cognitive fluctuation in patientswith neurocognitive disorder with Lewy bodies(NCDLB):the Mayo Fluctuations Scale-Thai version

Background Prevalence of neurocognitive disorder with Lewy bodies （NCDLB） is low in Asian populations, which may partially refect its diagnostic diffculty. The Mayo Fluctuations Scale, a short questionnaire that evaluates cognitive fuctuation, has been shown to signifcantly differentiate NCDLB from Alzheimer＇s disease.Aim This study aimed to develop the Mayo Fluctuations Scale-Thai version and assess its validity to screen NCDLB in an elderly population.Methods The Mayo Fluctuations Scale was translated into Thai. The process involved back-translation, cross-cultural adaptation, feld testing of the prefnal version, as well as fnal adjustments. From all patients attending the Psychiatric and Memory Clinic at Ramathibodi Hospital, 135 patients accompanied by their primary caregivers were included. Caregivers were interviewed by research assistants using a four-item scale, and psychiatrists determined patients＇ diagnosis based on the diagnostic and statistical manual of mental disorders （DSM）-5 criteria. Evaluations performed by psychiatrists and research assistants were blinded.Results Seventeen participants had been diagnosed with major NCDLB. At a cut-off score of 2 or over, the Mayo Fluctuations Scale exhibited excellent performance to differentiate major NCDLB from other major neurocognitive disorders （NCDs）, with a sensitivity of 94.1% and a specifcity of 71.4%, and acceptable performance to differentiate mild NCDLB from other mild NCDs, with a sensitivity of 60% and a specifcity of 93.1%.Conclusion The Mayo Fluctuations Scale-Thai version is an excellent screening tool for major NCDLB and an acceptable tool that may be used with other additional tests for mild NCDLB. The tool is practical for use in memory and psychiatric clinics. Further validation studies in participants with other specifc clinical conditions are required.

Verbal Communication in HIV-1 Patients： A New Perspective on the Study of Cognitive Disorders

The aims were： （1） to study verbal communication skills presenting with verbal communication deficits by applying the MEC in HIV-1 patients, and （2） to analyze the proportion of patients Protocol. The authors evaluated 20 patients over 18 years of age HIV-1 positive; native speakers of Spanish; without alterations in language acquisition, reading, writing or history of neurological or psychiatric disease; patients undergoing antiretroviral treatment （not efavirenz） with viral load 〉 50 copies/mL, and patients not undergoing treatment. Their verbal communication abilities were evaluated with Protocol MEC. The results demonstrate that some of the skills evaluated are more vulnerable in HIV-1 patients. The tasks that showed the most frequent and systematic deficits among patients were discourse-level tasks and those that evaluate lexical semantic processing. The authors compared patients＇ performances with the ＂cut-off＇. The scores were turned into score Z. A hierarchic cluster analysis was carried out to identify subgroups with different profiles according to the areas that were affected. The detection of communication deficit profiles in HIV-1 patients would be the starting point for the identification of disorders and the admission of the patients to health care system. This research constitutes an initial approach towards the identification of clinical profiles among HIV-1 patients.

Aspartic acid in the hippocampus:a biomarker for postoperative cognitive dysfunction

This study established an aged rat model of cognitive dysfunction using anesthesia with 2% iso- flurane and 80% oxygen for 2 hours. Twenty-four hours later, Y-maze test results showed that isoflurane significantly impaired cognitive function in aged rats. Gas chromatography-mass spectrometry results showed that isoflurane also significantly increased the levels of N,N-diethy- lacetamide, n-ethylacetamide, aspartic acid, malic acid and arabinonic acid in the hippocampus of isoflurane-treated rats. Moreover, aspartic acid, N,N-diethylacetamide, n-ethylacetamide and malic acid concentration was positively correlated with the degree of cognitive dysfunction in the isoflurane-treated rats. It is evident that hippocampal metabolite changes are involved in the formation of cognitive dysfunction after isoflurane anesthesia. To further verify these results, this study cultured hippocampal neurons in vitro, which were then treated with aspartic acid （100 μmol/L）. Results suggested that aspartic acid concentration in the hippocampus may be a biomarker for predicting the occurrence and disease progress of cognitive dysfunction.

Adaptive and regulatory mechanisms in aged rats with postoperative cognitive dysfunction

Inflammation may play a role in postoperative cognitive dysfunction. 5＇ Adenosine monophos- phate-activated protein kinase, nuclear factor-kappa B, interleukin-1β, and tumor necrosis factor-a are involved in inflammation. Therefore, these inflammatory mediators may be involved in postoperative cognitive dysfunction. Western immunoblot analysis revealed 5＇ adenosine mo- nophosphate-activated protein kinase and nuclear factor-kappa B in the hippocampus of aged rats were increased 1-7 days after splenectomy. Moreover, interleukin-1β and tumor necrosis fac- tor-α were upregulated and gradually decreased. Therefore, these inflammatory mediators may participate in the splenectomy model of postoperative cognitive dysfunction in aged rats.

Effects of Total Intravenous Anesthesia and Static Aspiration Combined General Anesthesia on Postoperative Cognitive Function and Psychological State of Elderly Patients with Esophageal Cancer

Objective: To compare the effects of total intravenous anesthesia and static aspiration combined general anesthesia on postoperative cognitive function and psychological state of elderly esophageal cancer patients. Methods: From July 2020 to April 2021, 180 elderly patients who underwent radical esophageal cancer surgery in our hospital were randomly divided into 90 cases in the control group and 90 in the observation group. The control group used static aspiration compound general anesthesia, and the patients in the observation group used intravenous anesthesia to compare the cognitive function and psychological state of the two groups of patients. Results: There was no statistical difference in the cognitive function score of patients in the observation group 30 minutes before anesthesia, 1 h and 24 hours after anesthesia compared with that in the control group, P > 0.05;there was no statistical difference between the Hamilton Anxiety Scale (HAMA) scores 30 minutes before and 24 hours after anesthesia in the observation group compared with the control group, P > 0.05;the cognitive function score of patients in the observation group of 4 h after surgery and 12 h after operation was significantly higher than that of the control group;the HAMA scores of patients in the observation group of 1 h, 4 h and 12 h after surgery were significantly lower than that of the control group, P Conclusion: The application of total intravenous anesthesia in elderly patients with esophageal cancer surgery can reduce the impact of anesthesia on their cognitive function and psychological state, which is worth popularizing and applying in clinical practice.

Evaluation of Efficacy and Safety of Electro-acupuncture Precondition on Postoperative Cognitive Dysfunction (POCD) Following Knee Replacement in Elderly: A Randomized Controlled Trial

OBJECTIVE: To investigate that whether electro-acupuncture(EA) precondition can reduce the incidence of postoperative cognitive dysfunction(POCD) following knee replacement and its safety in elderly. METHODS: A total of 60 participants met the inclusion criteria were enrolled in a randomized controlled trial with the ratio of 1:1, with 30 cases in the treatment group and 30 cases in the control group. The participants in the treatment group were provided with realEA therapy whereas participants in control group were provided with placebo-EA therapy. Interventions were offered 5 days prior to the surgery, once daily, and for a total of 5 days. The scores of Mini-Mental State Examination(MMSE), and contents of serumal inflammatory cytokines including interleukin 1β(IL-1β) and tumor necrosis factor-α(TNF-α) were observed at 24 hours prior-and posterior-to the surgery respectively for assessing the incidence of POCD among patients. Meanwhile, adverse effects were monitored and recorded. RESULTS:(1) After surgery, both treatment group and control group showed a significant decrease in MMSE global scores(P < 0.001, < 0.001, respectively), and the score in control group decreased more significantly than that in treatment group(P < 0.05);(2) Contents of serumal IL-1β and TNF-α were significantly increased in both groups after 24 hours posterior to the surgery(P < 0.001), and the contents in control group increased more significantly than that in treatment group(P < 0.001);(3) After surgery, the incidence of POCD was 20% in treatment group versus 36.67% in control group. There was no statistical difference between 2 groups(P > 0.05);(4) No serious adverse events were reported in this trial, except 1 patient from treatment group had a slight hematoma after receiving acupuncture. CONCLUSION: EA precondition might reduce cognitive impairments after 24 hours posterior to knee replacement surgery in elderly through inhibiting expression of inflammatory cytokines, including both IL-1β and TNF-α. However, there is insufficient evidence to support that EA precondition could reduce incidence of POCD.

Increased Cerebral Cortex Perfusion in Stroke Patients with Cognitive Disorder Following Cilostazol Administration, Two Cases Report

Objective: In our search for a new augmentation therapy for stroke patients, we administered cilostazol, an antiplatelet agent. Subjects: The patients suffered from mild hemiparesis or cognitive disorder showing reduced cerebral perfusion in the prefrontal cortex. Methods: We evaluated the functional cerebral blood flow (CBF) before and after the administration of cilostazol using near-infrared resonance spectroscopy (NIRS) during a verbal fluency task (VFT). Results: For the patient with cognitive disorder, statistically significant improvements were observed in the number of generated words in the VFT before and after administration of 50 mg cilostazol (p 0.05, Mann-Whitney U test). Another patient without cognitive disorder, however, showed no significant VFT improvement after administration of cilostazol. Effect size data revealed large or very large effects of cilostazol on brain activation (oxy-Hb levels) at the affected side prefrontal cortex for both patients. The patient with cognitive disorder showed significant improvement in VFT performance as well as an increase in bilateral prefrontal CBF after cilostazol administration. Discussion: These findings suggest that, for patients with cerebrovascular lesions suffering from cognitive disorder, cilostazol may be promising as a drug to improve cognitive function in addition to preventing recurrent cerebral infarction.

NP-23 Cascade Events for Delayed Postoperative Cognitive Dysfunction

Background:Postoperative cognitive dysfunction(POCD)can occur in patients with cardiac and non-cardiac surgeries.About 20%to 40%patients develop POCD at hospital discharge(a few days after surgery,acute POCD)and 10%elderly patients(>60 years old)have POCD at 3 months after surgery(delayed POCD).Age and degree of education are risk factors for delayed POCD.It has been shown that POCD is associated with increased mortality.Patients with POCD have a longer hospital stay and an increased rate of leaving job market.Thus,POCD is a very significant clinical syndrome during the perioperative period,which is recognized only in recent years.We and others have shown that neuroinflammation is a critical neuropathological process for POCD.However,neuroinflammation lasts for a few days after surgery.It is not known how such a short-lived neuropathological process lead to POCD a few months after surgery.To address this issue,a series of experiments were performed in my laboratory.Methods:Rats or mice were subjected to common carotid arterial exposure,a surgical component of carotid endarterectomy that is often performed in elderly patients.Their learning and memory were assessed at least one week after surgery.Their blood and brain tissues were harvested at various time after surgery for biochemical and structural analyses.Results:The surgery induced an increase of proinflammatory cytokines in the blood.The surgery also increased the expression of active matrix metallopeptidase 9(MMP-9)and its activity in the brain.This surgery induced POCD and neuroinflammation in wild-type mice but not in the MMP-9 knockout mice.P2X7 receptors and inflammasome were activated by the surgery.Inhibition of P2X7 receptors and P2X7 receptor knockout abolished POCD and neuroinflammation after surgery.The surgery decreased growth factor production and inhibition of neuroinflammation attenuated this decrease.The decreased growth factor expression occurred at 3 to 5 days after the surgery.Surgery increased histone deacetylase activity and inhibition of histone deacetylase attenuated the decrease of growth factor expression and the development of POCD.The surgery decreased neurogenesis in the hippocampus and application of growth factors to the brain attenuated this decrease and POCD.This decreased neurogenesis was observed 3 weeks after surgery.Finally,surgery impaired dendritic arborization that was assessed 3 weeks after surgery.Inhibition of histone deacetylases attenuated this impairment and POCD.Conclusion:Surgery induces a delayed POCD in rodents.Surgery results in systemic inflammation,which then activates MMP-9 to damage the brain-blood barrier to facilitate the systemic inflammation to be transmitted to the brain.Proinflammatory signals in the blood activate P2X7 receptors to induce neuroinflammation that inhibits growth factor expression through epigenetic regulation.Reduced growth factor expression results in decreased neurogenesis and dendritic arborization that then ultimately lead to the delayed POCD.Thus,surgery activates a series of cascade events to induce the delayed POCD.

Effects of Different Doses of BDNF on Postoperative Cognitive Function in Aged Rats Undergoing Abdominal Surgery

Objective:To investigate the effects of different doses of BDNF on postoperative cognitive function in aged rats undergoing abdominal surgery.Methods:72 aged healthy male SD rats of SPF grade were selected.According to the random number table method,the rats were randomly divided into the control group,model group,low dose BDNF injection group,and high dose BDNF injection group,with 18 rats in each group.The model group,low dose group,and high dose group underwent abdominal surgery after anesthesia,and 5μL/time of BDNF was intranasally administered to the rats in the low dose and high dose groups 6 hours after abdominal surgery,of which the dose of the low dose group was 0.1 g/L,while that of the high dose group was 0.2 g/L.The drug was administered alternately through both nostrils,with an interval of 2 minutes each time,for 5 times.The control group did not undergo surgery after anesthesia.The escape latency and swimming distance of the four groups of rats were compared before surgery,the first day,the third day,and the seventh day after surgery;similarly,the BDNF protein expression level in the hippocampus of the four groups of rats was compared on the first day,the third day,and the seventh day after surgery.Results:The escape latency and swimming distance of the control group were not statistically significant on the first day,the third day,and the seventh day after surgery,p>0.05;the escape latency and swimming distance of the model group,low dose group,and high dose group on the first day,the third day,and the seventh day after surgery were statistically significant,p<0.05.Before surgery,the escape latency and swimming distance of the four groups were not statistically significant,p>0.05;on the first day,the third day,and the seventh day after surgery,the escape latency and swimming distance of the model group>low dose group>high dose group>control group,p<0.05.The BDNF protein expression level in the hippocampus of the control group on the first day,the third day,and the seventh day after surgery showed no statistical significance p>0.05;the expression level of BDNF protein in the hippocampus of the model group,low dose group,and high dose group on the first day,the third day,and the seventh day after surgery was statistically significant,p<0.05.On the first day,the third day,and the seventh day after surgery,the expression level of BDNF protein in the hippocampus of the model group<low dose group<high dose group<control group,p<0.05.Conclusion:Compared with 0.1 g/L of BDNF,0.2 g/L of BDNF can improve the postoperative cognitive function of aged rats undergoing abdominal surgery.

Correlation Analysis Between BDNF and Postoperative Cognitive Dysfunction in Aged Rats

Objective:To investigate the relationship between BDNF and postoperative cognitive dysfunction among aged rats.Methods:36 SPF healthy aged male SD rats were randomly assigned to a control group and a model group,respectively,with 18 rats in each group.Abdominal exploration was performed on the rats in the model group after anesthesia,while the rats in the control group were not operated on after anesthesia.The escape latency and swimming distance of the two groups were analyzed on a day prior to surgery as well as on the first day,third day,and seventh day following surgery;the expression levels of BDNF protein in the hippocampus of rats in the two groups were compared on the first day,third day,and seventh day following surgery;the correlation between BDNF and escape latency and swimming distance was analyzed.Results:The escape latency and swimming distance of the rats in the control group on a day prior to surgery,the first day,third day,and seventh day following surgery did not differ significantly(p>0.05),but those in the model group had significant behavioral difference(p<0.05).On a day prior to surgery,the rats in both groups showed no significant behavioral difference in escape latency and swimming distance(p>0.05),but on the first day,third day,and seventh day following surgery,the escape latency and swimming distance of the rats in the model group were significantly longer than those in the control group(p<0.05).In the control group,there was no significant difference in the protein expression of BDNF in the hippocampus of rats on the first day,third day,and seventh day following surgery,but there was significant difference in the model group.On the first day,third day,and seventh day following surgery,the BDNF protein expression level in the rats’hippocampus of the control group was significantly higher than that of the model group(p<0.05).The data from Pearson correlation analysis confirmed that BDNF protein expression is negatively correlated with escape latency(r=-0.567,p<0.001)and swimming distance(r=-0.623,p<0.001).Conclusion:In aged rats,the BDNF protein expression level decreases,and the degree of cognitive dysfunction increases after surgery.

Effects of Surgical Anesthesia on Postoperative Cognitive Function of Elderly Patients

Postoperative cognitive dysfunction in elderly patients is a common complication after surgical anesthesia.The occurrence of complications is also related to many other factors,and the cause is still unclear.This paper reviews the influencing factors and corresponding measures for postoperative cognitive function of elderly patients caused by anesthesia.