Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and obstructive sleep apnea: a cross-sectional study from NHANES.

BACKGROUND: Obstructive Sleep Apnea (OSA) is a widespread sleep disturbance linked to metabolic and cardiovascular conditions. The Non-High-Density Lipoprotein Cholesterol to High-Density Lipoprotein Cholesterol Ratios (NHHR) has been proposed as being a potential biomarker to gauge cardiovascular risk. However, its relationship with OSA remains unclear. METHODS: This survey investigated the link NHHR to OSA in American citizens aged 20 and older using information collected via the National Health and Nutrition Examination Survey (NHANES) during the years 2017 to 2020. Logistic regression models with multivariable adjustments were employed to assess this relationship. Nonlinear associations were explored using smooth curve fitting, with a two-part linear regression model identifying a threshold effect. Subgroup analyses were conducted to evaluate population-specific differences. RESULTS: The survey encompassed 6763 participants, with an average age of 50.75 ± 17.32. The average NHHR stood at 2.74, accompanied by a standard deviation of 1.34, while the average frequency of OSA was 49.93%. Upon adjusting for covariates, each unit increase in NHHR may be associated with a 9% rise in OSA incidence. (95% confidence intervals 1.04-1.14; P < 0.0001). Notably, a U-shaped curve depicted the NHHR-OSA relationship, with an inflection point at 4.12. Subgroup analyses revealed consistent associations, with educational attainment and diabetes status modifying the NHHR-OSA relationship. CONCLUSION: The study highlights NHHR as a potential tool for OSA prediction, presenting avenues for advanced risk evaluation, tailored interventions, personalized treatment approaches, and preventive healthcare.

Anesthesia and surgery-induced elevation of CSF sTREM2 is associated with early cognitive dysfunction after thoracoabdominal aortic dissection surgery.

PURPOSE: Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) concentration is increased in cerebrospinal fluid (CSF) in early symptomatic phase of Alzheimer's disease (AD). This study investigated whether CSF sTREM2 has a relationship with early cognitive dysfunction following surgery in cardiac surgery patients. METHODS: A total of 82 patients undergoing thoracoabdominal aortic replacement were recruited in this study. Neuropsychological testing battery was conducted before and after surgery. Postoperative cognitive dysfunction (POCD) was defined as a Z-score > 1.96 on at least 2 different tests or Telephone Interviews for Cognitive Status-Modified (TICS-M) score < 27. The CSF and serum sTREM2, Aß42, T-tau and P-tau were collected and measured by ELISA on day before surgery and postoperative day 3. RESULTS: Patients were classified into POCD (n = 34) and non-POCD (n = 48) groups according to Z-score. Compared to non-POCD group, the levels of CSF sTREM2 (p < 0.001) and serum sTREM2 (p = 0.001) were significantly higher in POCD group on postoperative day 3. The levels of Aß42 (p = 0.005) and Aß42/T-tau ratio (p = 0.036) were significantly lower in POCD group on postoperative day 3. Multivariate logistic regression analysis revealed that higher value of postoperative CSF sTREM2 (odds ratio: 1.06, 95% confidence interval: 1.02-1.11, p = 0.009), age (OR: 1.15, 95%CI: 1.03-1.28, p = 0.014) and POD duration (OR: 2.47, 95%CI: 1.15-5.29, p = 0.02) were the risk factors of POCD. CONCLUSION: This study indicates that anesthesia and surgery-induced elevation of CSF sTREM2 is associated with an increased risk of early cognitive dysfunction following surgery.

A comparison of paravertebral block, erector spinae plane block and the combination of erector spinae plane block and paravertebral block for post-operative analgesia after video-assisted thoracoscopic surgery: A randomised controlled trial.

BACKGROUND: This study was to determine the analgesic effect of ultrasound-guided erector spinae plane block (ESPB) and paravertebral block (PVB) as well as the combination of PVB and ESPB (P + E) after video-assisted thoracoscopic surgery (VATS). PATIENTS AND METHODS: Patients were randomly assigned to receive ESPB, PVB or PVB combined with ESPB with 0.5% ropivacaine (20 ml). The primary outcomes were cumulative hydromorphone consumption and Visual Analogue Scale (VAS) scores at rest and while coughing at 0 h, 12 h, 24 h, 48 h and 72 h postoperatively. The secondary outcomes were effective PCA usage count and rescue analgesia requirement at the same time points. RESULTS: The median (interquartile range) hydromorphone consumption, including converted oxycodone, was significantly different at 48 h postoperatively among the three groups (ESPB, 10.24 [9.53-11.71] mg; PVB, 9.94 [9.19-10.75] mg; P + E, 9.44 [8.96-9.97] mg; P = 0.011). Hydromorphone consumption in P + E group was lower compared with that in ESPB group at 12 h, 24 h and 48 h (P < 0.001, P = 0.004 and P = 0.003, respectively). VAS scores at rest were significantly higher for ESPB group compared to P + E group at 0 h postoperatively (P = 0.009). VAS scores while coughing were significantly higher for ESPB group compared to P + E group at 0 h and 12 h postoperatively (P = 0.015 and P < 0.001) and to the PVB group at 12 h postoperatively (P = 0.002). The effective PCA usage count in P + E group was lower than in ESPB group in 0-12 h (P < 0.001). More patients needed rescue analgesia in ESPB group compared to those in P + E group in 0-12 h, 0-24 h and 0-48 h (P = 0.022, 0.035 and 0.035, respectively). CONCLUSIONS: Ultrasound-guided PVB combined with ESPB provided superior analgesia to ESPB for VATS. The combination of PVB and ESPB had a similar analgesic effect compared with PVB alone.

Autophagy Dysfunction and mTOR Hyperactivation Is Involved in Surgery: Induced Behavioral Deficits in Aged C57BL/6J Mice.

Autophagy is crucial for cell survival, development, division, and homeostasis. The mammalian target of rapamycin (mTOR), which is the foremost negative controller of autophagy, plays a key role in many endogenous processes. The present study investigated whether rapamycin can ameliorate surgery-induced cognitive deficits by inhibiting mTOR and activating autophagy in the hippocampus. Both adult and aged C57BL/6J mice received an intraperitoneal injection of rapamycin (10 mg/kg/day) for 5 days per week for one and a half months. Mice were then subjected to partial hepatectomy under general anesthesia. Behavioral performance was assessed on postoperative days 3, 7, and 14. Hippocampal autophagy-related (Atg)-5, phosphorylated mTOR, and phosphorylated p70S6K were examined at each time point. Brain derived neurotrophic factor (BDNF), synaptophysin, and tau hyperphosphorylation (T396) in the hippocampus were also examined. Surgical trauma and anesthesia exacerbated spatial learning and memory impairment in aged mice on postoperative days 3 and 7. Following partial hepatectomy, the levels of phosphorylated mTOR, phosphorylated 70S6K, and phosphorylated tau were all increased in the hippocampus. A corresponding decline in BDNF and synaptophysin were observed. Rapamycin treatment restored autophagy function, attenuated phosphorylation of tau protein, and increased BDNF and synaptophysin expression in the hippocampus of surgical mice. Furthermore, surgery and anesthesia induced spatial learning and memory impairments were also reversed by rapamycin treatment. Autophagy impairments and mTOR hyperactivation were detected along with surgery-induced behavioral deficits. Inhibiting the mTOR signaling pathway with rapamycin successfully ameliorated surgery-related cognitive impairments by sustaining autophagic degradation, inhibiting tau hyperphosphorylation, and increasing synaptophysin and BDNF expression.

Anesthesia Considerations and Infection Precautions for Trauma and Acute Care Cases During the COVID-19 Pandemic: Recommendations From a Task Force of the Chinese Society of Anesthesiology.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide. During the ongoing COVID-19 epidemic, most hospitals have postponed elective surgeries. However, some emergency surgeries, especially for trauma patients, are inevitable. For patients with suspected or confirmed COVID-19, a standard protocol addressing preoperative preparation, intraoperative management, and postoperative surveillance should be implemented to avoid nosocomial infection and ensure the safety of patients and the health care workforce. With reference to the guidelines and recommendations issued by the National Health Commission and Chinese Society of Anesthesiology, this article provides recommendations for anesthesia management of trauma and emergency surgery cases during the COVID-19 pandemic.

Upregulation of TREM2 Ameliorates Neuroinflammatory Responses and Improves Cognitive Deficits Triggered by Surgical Trauma in Appswe/PS1dE9 Mice.

BACKGROUND/AIMS: TREM2 plays a crucial role in modulating microglial function through interaction with DAP12, the adapter for TREM2. Emerging evidence has demonstrated that TREM2 could suppress neuroinflammatory responses by repression of microglia-mediated cytokine production. This study investigated the potential role of TREM2 in surgery-induced cognitive deficits and neuroinflammatory responses in wild-type (WT) and APPswe/PS1dE9 mice. METHODS: Adult APPswe/PS1dE9 transgenic male mice (a classic transgenic model of Alzheimer's disease, 3 months old) and their age-matched WT mice received intracerebral lentiviral particles encoding the mouse TREM2 gene and then were subjected to partial hepatectomy at 1 month after the lentiviral particle injection. The behavioral changes were evaluated with an open-field test and Morris water maze test on postoperative days 3, 7, and 14. Hippocampal TREM2, DAP12, and interleukin (IL)-1ß were measured at each time point. Ionized calcium-binding adapter molecule 1 (Iba-1), microglial M2 phenotype marker Arg1, synaptophysin, tau hyperphosphorylation (T396), and glycogen synthase kinase-3ß (GSK-3ß) were also examined in the hippocampus. RESULTS: Surgical trauma induced an exacerbated cognitive impairment and enhanced hippocampal IL-1ß expression in the transgenic mice on postoperative days 3 and 7. A corresponding decline in the levels of TREM2 was also found on postoperative days 3, 7, and 14. Overexpression of TREM2 downregulated the levels of IL-1ß, ameliorated T396 expression, inhibited the activity of GSK-3ß, and improved sickness behavior. Increased Arg1 expression and a high level of synaptophysin were also observed in the transgenic mice following TREM2 overexpression. CONCLUSION: The downregulation of TREM2 exacerbated surgery-induced cognitive deficits and exaggerated neuroinflammatory responses in this rodent model. Overexpression of TREM2 potentially attenuated these effects by decreasing the associated production of proinflammatory cytokines, inhibiting tau hyperphosphorylation, and enhancing synaptophysin expression.

An update on the management of postoperative nausea and vomiting.

Postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting (PDNV) remain common and distressing complications following surgery. PONV and PDNV can delay discharge and recovery and increase medical costs. The high incidence of PONV has persisted in part because of the tremendous growth in ambulatory surgery and the increased emphasis on earlier mobilization and discharge after both minor and major operations. Pharmacological management of PONV should be tailored to the patients' risk level using the PONV and PDNV scoring systems to minimize the potential for these adverse side effects in the postoperative period. A combination of prophylactic antiemetic drugs should be administered to patients with moderate-to-high risk of developing PONV in order to facilitate the recovery process. Optimal management of perioperative pain using opioid-sparing multimodal analgesic techniques and preventing PONV using prophylactic antiemetics are key elements for achieving an enhanced recovery after surgery. Strategies that include reductions of the baseline risk (e.g., adequate hydration, use of opioid-sparing analgesic techniques) as well as a multimodal antiemetic regimen will improve the likelihood of preventing both PONV and PDNV.

An update on pain management for elderly patients undergoing ambulatory surgery.

PURPOSE OF REVIEW: The aim of this review is to provide an overview of the drugs and techniques used for multimodal postoperative pain management in the older population undergoing surgery in the ambulatory setting. RECENT FINDINGS: Interest has grown in the possibility of adding adjuncts to a single shot nerve block in order to prolong the local anesthetic effect. The rapid and short-acting local anesthetics for spinal anesthesia are potentially beneficial for day-case surgery in the older population because of shorter duration of the motor block, faster recovery, and less transient neurologic symptoms. Another recent advance is the introduction of intravenous acetaminophen, which can rapidly achieve rapid peak plasma concentration (<15 min) following infusion and analgesic effect in ∼5 min with a duration of action up to 4 h. SUMMARY: The nonopioid analgesic therapies will likely assume an increasingly important role in facilitating the recovery process and improving the satisfaction for elderly ambulatory surgery patients. Strategies to avoid the use of opioids and minimize opioid-related side-effects is an important advance as we expand on the use of ambulatory surgery for the aging population.

Co-expression of Oct-4 and Nestin in human breast cancers.

The aim is to investigate the clinical implications of the Oct-4 and Nestin protein in human breast cancers. A total of 346 cases including 26 fresh and 320 paraffin-embedded tumor tissues were selected for characterizing the frequency of CD44(+)CD24(-) tumor cells by flow cytometry and the differential expression of the stem cell-related genes between CD44(+)CD24(-) and non-CD44(+)CD24(-) tumor cells was analyzed by PCR Array and immunofluorescence. In comparison with the non-CD44(+)CD24(-) tumor cells, the CD44(+)CD24(-), particularly for those with high percentage of Oct-4(+) and Nestin(+), tumor cells had higher tumorigenicity by forming mammospheres in vitro. More importantly, 42 (13.125%) out of 320 tumor tissues were positive for Oct-4 and Nestin staining. Universal analysis and multivariate analysis revealed that the expression of Oct-4 and Nestin was associated significantly with younger age, pathogenic degrees, lymph node metastasis and triple-negative breast cancer independently (P < 0.05) as well as shorter survival (P = 0.001). Oct-4 and Nestin were important regulators of the development of breast cancer, and Oct-4 and Nestin may be used as predictors for the prognosis of breast cancers.

A comparison of the analgesic efficacy of serratus anterior plane block vs. paravertebral nerve block for video-assisted thoracic surgery: a randomized controlled trial.

INTRODUCTION: Patients who undergo video-assisted thoracic surgery (VATS) frequently experience moderate to severe postoperative pain. Serratus anterior plane block (SAPB) is a relatively novel technique that can block the lateral cutaneous branches of the intercostal nerves as well as the long thoracic nerve. AIM: To evaluate the analgesic efficiency of deep serratus plane block (DSPB) and superficial serratus anterior plane block (SSPB) as well as paravertebral nerve block (PVB) in patients undergoing VATS. MATERIAL AND METHODS: A total of 74 patients aged 16-80 undergoing VATS were randomized to receive either DSPB or SSPB as well as PVB. Ultrasound (US) guided DSPB or SSPB as well as PVB was performed preoperatively on the patients according to their groups. All patients were provided with patient-controlled intravenous analgesia (PCIA) for postoperative analgesia. The primary outcomes were the levels of postoperative pain at rest and on coughing evaluated by the visual analog scale (VAS), and intraoperative and postoperative opioid consumption. The secondary outcomes included PCIA pressing times, side effects and satisfaction with analgesia, duration of nerve block, intraoperative hemodynamic changes and vasoactive drug dosage. RESULTS: No significant differences of VAS score were found. During the operation, PVB reduced consumption of opioids (27.23 ±5.10 mg) compared to DSPB (31.20 ±3.80 mg) and SSPB (32.61 ±5.28 mg). The effective pressing times of PCIA in the SSPB group (0.18 ±0.65) were significantly lower compared to the PVB group (1.09 ±1.50) at 12 h postoperatively. Accordingly, SSPB also reduced the dosage of PCIA (26.55 ±4.72 ml) compared to PVB (31.45 ±7.60 ml). Time of the PVB procedure was longer (11.14 ±1.66 min) than DSPB (5.68 ±1.10 min) and SSPB (4.77 ±1.04 min). CONCLUSIONS: DSPB and SSPB are easy to perform and can serve as a promising alternative technique to PVB that may offer comparable analgesic effectiveness for patients undergoing VATS.

TREM2 improves neurological dysfunction and attenuates neuroinflammation, TLR signaling and neuronal apoptosis in the acute phase of intracerebral hemorrhage.

Neuroinflammation contributes to secondary brain injury following intracerebral hemorrhage (ICH). Triggering receptor expressed on myeloid cells 2 (TREM2) confers strong neuroprotective effect by suppressing neuroinflammatory response in experimental ischemic stroke. This study aimed to clarify the neuroprotective role of TREM2 and potential underlying mechanism in a mouse model of ICH and in vitro. Adeno-associated virus (AAV) and green fluorescent protein-lentivirus (GFP-LV) strategies were employed to enhance TREM2 expression in the C57/BL6 mice and BV2 cells, respectively. The adult male C57/BL6 mice were subjected to ICH by administration of collagenase-IV in 1 month after the AAV particles injection. An in vitro ICH model was performed with oxygen hemoglobin in BV2 cells. Toll-like receptor 4 (TLR4) antagonist TAK242 was applied at 6 h following ICH. Neurological function, TREM2, pro-inflammatory cytokines, brain water content and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were evaluated at 24 h following ICH. TLR4, NF-κB and mitogen-activated protein kinases (MAPK) signaling pathways were also determined by Western blot analysis at the same time point. The levels of TREM2 were increased at 12 h, peaked at 24 h and recovered on 7d following ICH. TREM2 overexpression ameliorated ICH induced neurological dysfunction, inhibited neuroinflammation, and attenuated apoptosis and brain edema. Further mechanistic study revealed that TREM2 overexpression inhibited TLR4 activation and NF-κB and MAPK signaling pathways. ICH increased the percentage of TUNEL-positive cells, which was markedly decreased by TREM2 overexpression. A similar improvement was also observed by the administration of TAK242 following ICH. TREM2 improves neurological dysfunction and attenuates neuroinflammation and neuronal apoptosis in the acute phase of ICH, which is, at least in part, mediated by negatively regulating TLR4 signaling pathway. These findings highlight TREM2 as a potential target for early brain injury following ICH.

TREM2 ameliorates anesthesia and surgery-induced cognitive impairment by regulating mitophagy and NLRP3 inflammasome in aged C57/BL6 mice.

Postoperative cognitive dysfunction (POCD) is a major postoperative complication. Triggering receptor expressed on myeloid cells 2 (TREM2) exerts a neuroprotective function against neuro-inflammatory responses. The present study investigated the role of TREM2 in anesthesia and surgery-induced cognitive impairment and the potential related mechanism. Our results revealed that TREM2 was downregulated, coupled with activation of the NLRP3 inflammasome and subsequent IL-1ß expression on postoperative day 3. A corresponding decline in PSD-95 and BDNF was found at the same time point. The key regulator of mitophagy PINK1 and Parkin protein levels were significantly decreased following surgery and anesthesia. TREM2 overexpression partially reversed postoperative cognitive impairment and enhanced PSD-95 and BDNF expression. TREM2 overexpression also improved mitophagy function and inhibited activation of the NLRP3 inflammasome and associated production of IL-1ß. Our findings demonstrate that TREM2 rescues anesthesia and surgery-induced spatial learning and memory impairment and neuro-inflammation in aged C57/BL6 mice, which may be at least partially mediated through the activation of mitophagy and subsequent inhibition of the NLRP3 inflammasome.

TREM2 Ameliorates Lipopolysaccharide-Induced Oxidative Stress Response and Neuroinflammation by Promoting Sirtuin3 in BV2 Cells.

Triggering receptor expressed on myeloid cells 2 (TREM2) plays a crucial role in modulating microglial-mediated neuroinflammation. The NAD-dependent deacetylase protein Sirtuin 3 (SIRT3) regulates mitochondrial oxidative stress response and neuroinflammation. TREM2 deficiency impairs the denovo synthesis pathway of NAD+. Therefore, the aim of this study was to investigate the potential role of TREM2 and SIRT3 in LPS-induced oxidative stress and neuroinflammation in BV2 cells. Lentivirus vector-mediated TREM2 overexpression (TREM2-OE) and corresponding negative control vector (TREM2-NC) were synthesized. BV2 cells were treated with LPS and/or TREM2-OE. 3-TYP, a selective SIRT3 inhibitor, was applied to determine the role of SIRT3 in the anti-oxidant and anti-inflammatory effects of TREM2. TREM2, SIRT3, NLRP3 inflammasome, caspase-1, postsynaptic density-95 (PSD-95), and brain derived neurotrophic factor (BDNF) were measured by Western blot analysis. Superoxide dismutase (SOD) was tested by SOD Assay Kit. Reactive oxygen species (ROS) expression was examined by immunofluorescence. Interleukin 1ß (IL-1ß) was determined by ELISA. Contents of NAD+ and NADH were detected by WST-8 method. LPS (1ug/ml for 24 h) significantly decreased TREM2 expression at both RNA and protein levels (p < 0.01 and p < 0.05, respectively). Lower levels of SIRT3 protein and NAD+ were also detected following LPS stimulation (p < 0.05 and p < 0.05, respectively). LPS significantly enhanced ROS, NLRP3, caspase-1, and IL-1ß expression (p < 0.01, p < 0.05, p < 0.05, and p < 0.01, respectively). PSD-95 and BDNF expression were decreased triggered by LPS (p < 0.05 and p < 0.05, respectively). TREM2 overexpression enhanced NAD+ and SIRT3 protein expression following LPS challenge in BV2 cells (p < 0.01 and p < 0.05, respectively). TREM2 alleviated LPS-induced oxidative stress and neuroinflammation (p < 0.01 and p < 0.05, respectively). Similarly, TREM2 overexpression upregulated PSD-95 and BDNF expression (p < 0.05 and p < 0.05, respectively). The anti-oxidant and anti-inflammatory effects of TREM2 were partially abrogated by SIRT3 antagonist 3-TYP (p < 0.05 and p < 0.05, respectively). Similarly, selective SIRT3 inhibition also partially abrogated TREM2-induced BDNF protein upregulation (p < 0.05) but failed to influence PSD-95 protein expression following LPS stimulation. LPS induces oxidative stress and neuroinflammation in BV2 cells, which may be mediated in part by the downregulation of TREM2 and SIRT3. TREM2 overexpression ameliorates LPS-induced oxidative stress and neuroinflammation through enhancing SIRT3 function via NAD+.

Gut Microbial Metabolite Short-Chain Fatt Acids Partially Reverse Surgery and Anesthesia-Induced Behavior Deficits in C57BL/6J Mice.

Accumulating evidence has demonstrated that damages of gut microbiota are strongly associated with central nervous system (CNS) diseases, such as perioperative neurocognitive disorders (PND). The present study investigated the role of gut microbial metabolite short-chain fatty acids (SCFAs) in surgery-induced cognitive deficits and neuroinflammation in the hippocampus. Adult male C57BL/6J mice received either SCFA mixture or saline orally for 4 weeks, and then partial hepatectomy was performed. The fecal supernatant of surgical mice was transplanted to normal mice for 3 weeks. The Morris water maze (MWM) and open-field tests were used to evaluate behavioral performance on postoperative or post-transplantation days 3 and 7. In the MWM test, pretreatment with exogenous SCFAs partially reversed surgery-induced impairments in crossing times and the time spent in the target quadrant on postoperative day 3 (p < 0.05, p < 0.05, respectively). In the open-field test, compared with the surgical mice, exogenous SCFA administration prior to surgery partially improved the locomotor activity (p < 0.05) and anxiety-like behavior (p < 0.05) on postoperative day 3. Surgical trauma and anesthesia enhanced ionized calcium-binding adapter molecule 1 (Iba-1) expression (p < 0.001), increased the levels of interleukin (IL)-1ß (p < 0.001) and IL-6 (p < 0.001), and inhibited SCFA production (p < 0.001) on postoperative day 3. The expression of the brain-derived neurotrophic factor (BDNF) was also decreased (p < 0.001). Overall, surgical trauma and anesthesia exacerbated cognitive impairment, enhanced neuroinflammatory responses, and inhibited SCFA production. Pretreatment with SCFAs attenuated these effects partially by reversing microglial overactivation, inhibiting neuroinflammatory responses, and enhancing BDNF expression.

Protective effects of lithium treatment for spatial memory deficits induced by tau hyperphosphorylation in splenectomized rats.

1. Postoperative cognitive dysfunction has become more prevalent in recent years. We used a splenectomized rat model with postoperative spatial learning and memory deficits to investigate the role of tau hyperphosphorylation and glycogen synthase kinase-3ß (GSK-3ß) within the hippocampus. 2. Cognitive function was assessed in a Y-maze 1 day before and 1, 3 and 7 days after surgery. We measured site-specific phosphorylation of hippocampal tau (Thr-205 and Ser-396), GSK-3ß activity and expression of interleukin-1ß (IL-1ß), tumour necrosis factor-α (TNF-α) mRNA and protein as markers of inflammation. We also tested the effects of treatment with lithium chloride (LiCl), a GSK-3ß inhibitor. 3. Splenectomy was associated with learning and memory impairment 3 days later, as well as a rapid and massive hyperphosphorylation of hippocampal tau at Thr-205 and Ser-396, activated GSK-3ß, and increased IL-1ß and TNF-α expression. LiCl completely restored tau hyperphosphorylation to control levels. 4. These data from the splenectomized rat model suggest that inflammatory factors affect tau pathology through the GSK-3ß signalling pathway and that LiCl is a promising treatment for postoperative cognitive deficits.

Tau hyperphosphorylation is associated with memory impairment after exposure to 1.5% isoflurane without temperature maintenance in rats.

BACKGROUND AND OBJECTIVE: There is increasing interest in studying the role of tau hyperphosphorylation associated with memory impairment. We examined the involvement of tau hyperphosphorylation in memory impairment after hypothermia following isoflurane anaesthesia in rats. METHODS: Adult rats were randomly divided into three groups: the control group received no treatment and others were subjected to 1.5% isoflurane anaesthesia with or without temperature control for 2 h. On the day before anaesthesia and on postanaesthetic days 1, 3 and 7, cognitive functions were assessed in a Y-maze test paradigm. To find the relationship between memory results and tau, we measured the site-specific phosphorylation of tau at Thr-205 and Ser-396 and the activity of protein phosphatase 2A within the hippocampus. RESULTS: The spatial learning and memory of animals with hypothermia were impaired at day 1 after anaesthesia, compared with nonanaesthetized rats. Anaesthesia and hypothermia led to tau hyperphosphorylation at the Thr-205 and Ser-396 epitopes in the hippocampus. There was no significant difference in the protein phosphatase 2A activity between the control and the postanaesthetic rat hippocampal samples, whereas nearly 45% protein phosphatase 2A inhibition was detected in the anaesthetized without temperature maintenance rat samples. CONCLUSION: Our results indicate that tau phosphorylation is not a direct result of anaesthesia per se, but it is due to anaesthesia-induced hypothermia and this leads to the inhibition of phosphatase activity as well as tau hyperphosphorylation. Tau hyperphosphorylation is associated with the observed deficits in spatial learning and memory following anaesthesia in hypothermic rats.

Exendin-4 improves behaviorial deficits via GLP-1/GLP-1R signaling following partial hepatectomy.

Recent studies indicate that glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonists exhibit neurotrophic and neuroprotective effects. The aim of this study was to explore whether the GLP-1R agonist exendin-4 can alter surgery-induced behavioral deficits and exert neuroprotective effects via the activation of the hippocampal GLP-1/GLP-1R pathway. 120 male Sprague-Dawley rats (aged 18-20 months old) were randomly divided into four groups: control group, exendin-4 group, surgery group, and surgery + exendin-4 group. The animals received either exendin-4 (5 µg/kg/day) or saline intra-peritoneally for 14 days, and then were subjected to partial hepatectomy 24 h after the last injection. Behavioral changes were evaluated with Morris Water Maze and Open field testing on postoperative days 7 and 14. The levels of IL-1ß, NF-κB, Iba-1, Synaptophysin, GLP-1/GLP-1R, GSK-3ß, p-GSK-3ß (Ser9), p-Tau (Ser396), and p-Tau (Ser202/199) in the hippocampus were measured at the same time point. Surgical trauma induced an exacerbated spatial learning and memory impairment, increased the levels of depressive performance, and enhanced hippocampal NF-κB and IL-1ß expression in the aged rats on postoperative day 7. A corresponding decline in GLP-1R was also found following surgical challenge on postoperative day 7. Exendin-4 treatment partly reversed surgery-induced postoperative behavioral impairment, downregulated the levels of NF-κB and IL-1ß, ameliorated tau hyperphosphorylation and enhanced the activity of p-GSK-3ß (Ser9). Together, the downregulation of GLP-1R exacerbated surgery-induced behavior deficits. Exendin-4 treatment attenuated these effects by inhibiting neuroinflammation and tau hyperphosphorylation. These findings suggest that pretreatment with exendin-4 is a potential adjuvant for preventing surgery-induced behavioral deficits.

Downregulation of LncRNA TUG1 Inhibited TLR4 Signaling Pathway-Mediated Inflammatory Damage After Spinal Cord Ischemia Reperfusion in Rats via Suppressing TRIL Expression.

Toll-like receptor 4 (TLR4) and TLR4 interactor with leucine-rich repeats (TRIL) play a crucial role in the inflammatory response. This study investigated the role of long noncoding RNA taurine-upregulated gene 1 (lncRNA TUG1) in TRIL/TLR4 signaling in spinal cord ischemia reperfusion (IR) injury. IR injury was induced in experimental rats; knockdown of TUG1 and TRIL was induced by intrathecal injection of siRNAs and overexpression of TRIL was induced by pcDNA3.3-TRIL. The results showed that the mRNA levels of TUG1 were increased at 12 hours after IR; this was accompanied by increased expression of the TRIL- and TLR4-mediated NF-κB/IL-1ß signaling pathway. Activated microglia, detected with increased ionized calcium-binding adapter molecule 1 as a marker, exacerbated the hind-limb neurological impairment and blood-spinal cord barrier (BSCB) leakage after IR. TUG1 knockdown inhibited expression of TRIL and TLR4 signaling proinflammatory cytokines and microglial activation, and attenuated neurological deficit and BSCB leakage. TRIL knockdown inhibited the TLR4-mediated inflammatory response, while TRIL expression reversed the inhibited inflammatory effect caused by TUG1 knockdown. These data suggest that TUG1 knockdown inhibited inflammatory damage of the TLR4-mediated NF-κB/IL-1ß signaling pathway after IR via suppressing TRIL expression.

Surgical Trauma Exacerbates Cognitive Deficits and Neuroinflammation in Aged Rats: The Role of CX3CL1-CX3CR1 Signaling.

Age is the most prominent risk factor for the development of postoperative cognitive dysfunction. The present study investigated the role of CX3CL1-CX3CR1 signaling in age-related differences in surgery-induced cognitive deficits and neuroinflammation. Adult and aged male Sprague-Dawley rats were subjected to partial hepatectomy or partial hepatectomy with intracerebroventricular infusion of CX3CL1. On postoperative days 3, 7, and 14, the rats were subjected to an open field test and the Morris water maze test. Hippocampal interleukin-1ß, CX3CL1, CX3CR1, brain derived neurotrophic factor (BDNF), ionized calcium-binding adapter molecule 1 (Iba-1), and Arginase-1 (Arg1) levels were measured. Age exacerbated cognitive impairment and increased neuroinflammation following surgery. Surgery-induced decreases in CX3CL1 and CX3CR1 proteins were accompanied by increased microglial activation, as indicated by increased Iba-1 expression. Corresponding decline in Arg1 and BDNF levels were observed. Treatment with CX3CL1 decreased proinflammatory cytokines expression, increased BDNF and Arg1 levels in the brain, and enhanced behavioral recovery. The surgery-induced decreases in CX3CL1 and CX3CR1 expression exacerbated postoperative cognitive deficits and exaggerated neuroinflammatory responses in this rodent model. Treatment with CX3CL1 attenuated these effects, at least partly by inhibiting microglial activation, decreasing the associated production of proinflammatory cytokines, and enhancing BDNF expression.