Electroacupuncture ameliorates surgery-induced spatial memory deficits by promoting mitophagy in rats.

Background: This study sought to explore the mechanism underlying the therapeutic effects of electroacupuncture (EA) on spatial memory deficits caused by surgery. Methods: Hepatic apex resection was performed under propofol-based total intravenous anesthesia. Male Sprague-Dawley rats were subjected to EA treatment or EA + mitochondrial division inhibitor-1 (mdivi-1) treatment once a day for three consecutive days after surgery. The Morris water maze test was used to evaluate the spatial memory of the rats after surgery. Tissue from the hippocampus of each rat was frozen and used for transcriptomic and proteomic analyses to identify potential targets for EA treatment. Western blotting was used to confirm the protein expression levels. The levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP) were detected using commercial kits. The rat mitochondria were then isolated, and the activity of mitochondrial complex V was assessed. Results: EA attenuated surgery-induced spatial memory deficits on postoperative day 3, while these effects were reversed by treatment with the mdivi-1 (P<0.05). Ribonucleic acid (RNA)-sequencing revealed that EA upregulated multiple metabolic pathways and the phosphatidylinositol 3­kinas/protein kinase B signaling pathway. The proteomic and western blotting results suggested that the EA treatment substantially downregulated coiled-coil-helix-coiled-coil-helix domain containing 3 (ChChd3) expression in the hippocampus. The EA treatment significantly increased the autophagy-related protein levels, including phosphatase and tensin homolog-induced kinase 1, Parkin, MAP1LC3 (LC3), and Beclin1, and inhibited the production of ROS and inflammatory cytokine interleukin-1ß in the hippocampus (P<0.05). Conclusions: These results suggest that EA ameliorates postoperative spatial memory deficits and protects hippocampus from oxidative stress and inflammation through enhanced autophagy in an animal model of perioperative neurocognitive disorders (PNDs).

Electroacupuncture Alleviates Thalamic Pain in Rats by Suppressing ADCY1 Protein Upregulation.

BACKGROUND: Thalamic pain (TP), also known as central post-stroke pain, is a chronic neuropathic pain syndrome that follows a stroke and is a severe pain that is usually intractable. No universally applicable and effective therapies have been proposed. Emerging studies have reported that electroacupuncture (EA) can potentially be used as an effective therapy for the treatment of neuropathic pain. However, whether EA influences TP and if so, by what potential mechanism, remains poorly understood. OBJECTIVE: The aim of this study was to detect the efficacy of EA and explore possible mechanisms for treating TP. STUDY DESIGN: Controlled animal study. SETTING: The laboratory at the Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine. METHODS: Male Sprague Dawley rats were randomly divided into 3 groups (n = 15 / group): sham-operated (SH) group, thalamic pain model (TP) group, EA treatment (EA) group. After the TP rat model was successfully established, EA was used for intervention. During the experiment, the mechanical pain thresholds of rats were detected among the groups. The right thalamus of the rats was extracted on postoperative day 28 for RNA-sequencing (RNA-Seq) analysis to find the changes in gene expression in different groups of rats. The key genes were screened using reverse transcription-polymerase chain reaction (RT-PCR) detection and subsequently identified with western blotting and immunofluorescence. RESULTS: The mechanical withdrawal threshold (MWT) value of the right facial skin in the TP group and the EA group decreased significantly on the 3rd day after surgery, compared to the SH group (P < 0.01). From 7 to 28 days, the MWT value increased continually in the EA group; however, there was no significant change in the TP group. The results of RNA-seq showed that compared to the TP group, 377 genes changed in the EA group. Moreover, ADCY1 expression increased significantly in the TP group as compared to the SH group, while EA treatment reversed the expression of ADCY1. LIMITATIONS: In addition to ADCY1, the mechanism(s) of other signaling pathways in TP need to be explored in future research. CONCLUSIONS: EA treatment may promote the recovery of TP model rat by regulating ADCY1 expression.

A multicenter survey of perioperative anxiety in China: Pre- and postoperative associations.

OBJECTIVES: To describe patient characteristics associated with preoperative anxiety and subsequently assess the relationship between preoperative anxiety and postoperative anxiety, pain, sleep quality, nausea and vomiting. METHODS: The study collected data from patients undergoing elective operation from 12 hospitals in China. The State-Trait Anxiety Inventory (STAI) and the Athens Insomnia Scale (AIS) were used to assess anxiety and sleep quality before surgery. Evaluations of anxiety, pain, sleep quality, nausea and vomiting were quantified using the Visual Analogue Scale on postoperative days 1 and 2. RESULTS: Data from 997 patients were analyzed. Preoperatively, 258 (25.9%) patients had high anxiety (STAI-State>44). Multivariate analyses showed a significant relationship between high anxiety and female gender (OR: 1.66, 95% CI: 1.08-2.57, p = 0.02), highly invasive surgery (OR: 2.29, 95% CI: 1.29-4.06, p = 0.005), higher trait anxiety (OR: 1.24, 95% CI: 1.20-1.28, p < 0.001) and insomnia (AIS ≥ 6, OR: 1.79, 95% CI: 1.17-2.76, p = 0.008). Preoperative anxiety demonstrated a negative correlation with postoperative anxiety following highly invasive surgery; this became a positive relationship following less invasive surgery. Preoperative anxiety was also positively related to postoperative pain and poor sleep quality. The correlation between preoperative anxiety and postoperative nausea and vomiting was not statistically significant. CONCLUSION: Female gender, highly invasive surgery, higher trait anxiety and insomnia are independent risk factors for high preoperative anxiety. Surgical invasiveness influences association between pre- and postoperative anxiety. Higher preoperative anxiety is related to poorer sleep quality and more severe pain postoperatively.

Dexmedetomidine Reverses Postoperative Spatial Memory Deficit by Targeting Surf1 and Cytochrome c.

Anesthesia and surgery are associated with perioperative neurocognitive disorders (PND). Dexmedetomidine is known to improve PND in rats; however, little is known about the mechanisms. Male Sprague-Dawley rats were subjected to resection of the hepatic apex under propofol anesthesia to clinically mimic human abdominal surgery. The rats were divided into four groups: control group (C), anesthesia group (A), model group (M), and model + dex group (D). Cognitive function was evaluated with the Morris water maze (MWM). Neuronal morphology was observed with H&E staining, Nissl's staining and immunohistochemistry. Transcriptome analysis and quantitative real-time PCR were performed to investigate functional mitochondrial mRNA changes in the hippocampus. Protein levels were measured by Western blotting at 1, 3, and 7 days after surgery. Surgery-induced cognitive decline lasted for three days, but not seven days after surgery in the M group; however, rats in the D group were significantly improved by dexmedetomidine. No significant differences in the number of neurons were observed between the groups after surgery. Rats from the M group showed significantly greater expression levels of Iba-1 and GFAP compared with the C group and the D group. Rats in the M group demonstrated increased Surf1 and Cytochrome c expression on days 1 and 3, but not day 7; similar changes were not induced in rats in the D group. Dexmedetomidine appears to reverse surgery-induced behavior, mitigate the higher density of Iba-1 and GFAP, and downregulate the expression of Surf1 and Cytochrome c protein in the hippocampus of rats in a PND model.

Deep sternal wound infection after cardiac surgery: a comparison of three different wound infection types and an analysis of antibiotic resistance.

BACKGROUND: Deep sternal wound infection (DSWI) is a severe complication following cardiac surgery. We compared epidemiology, clinical features, and microbiology of three types of DSWI and examined the antibiotic resistance in DSWI patients. METHODS: From 2011 to 2015, 170 adult post-cardiac surgery DSWI patients were recruited for this study and underwent the pectoralis major muscle flap transposition in our department. RESULTS: Of 170 adult patients with DSWI (mean age of 54 years), the majority (99 patients, 58.2%) had type II DSWI. The three types of DSWI patients showed significant differences in terms of gender, smoking history, chronic obstructive pulmonary disease (COPD), length of intensive care unit (ICU) stay, and hospitalization cost (P<0.05). The most common symptoms of DSWI patients were fever and wound dehiscence accompanied by purulent secretions. Types I and II DSWI were more frequently associated with hypoproteinemia and high leucocyte count (P<0.05). Microbiological diagnosis was available for 77 of 170 patients (45.3%). Of 157 pathogens detected, 87 (55.4%) species of gram negative bacilli were identified and most commonly were Pseudomonas aeruginosa (25.5%) and methicillin-susceptible Staphylococcus aureus (20.4%). However, no statistically significant microbiological differences among the three DSWI types were observed (P>0.05). Notably, P. aeruginosa isolates showed 100% resistance to cefazolin and cefuroxime. Meanwhile, the resistance rate of Acinetobacter baumannii isolates to commonly used antibiotics was greater than 70%, while resistance rates of staphylococcus to penicillin-G were 100% and to clindamycin were over 70%. No isolates were resistant to vancomycin, linezolid, and tigecycline. CONCLUSIONS: Three types of DSWI exhibit differences in epidemiology and clinical features. P. aeruginosa and S. aureus are the most common pathogens in DSWI patients and antibiotic resistance is a serious concern in these patients. Therefore, prevention and treatment of DSWI should be closely tailored to clinical features, local microbiological characteristics, and resistance patterns of commonly encountered pathogens.

Ovarian Damages Produced by Aerosolized Fine Particulate Matter (PM2.5) Pollution in Mice: Possible Protective Medications and Mechanisms.

BACKGROUND: Ambient aerosol fine particulate matter (PM2.5) is associated with male reproductive toxicity in experiments and may have adverse effects in the female. However, studies evaluating the protective effects and precise mechanisms of aspirin, Vitamin C, Vitamin E, or ozone against toxic effects of PM2.5are sparse. This study was conducted to investigate the possible protective effects and mechanisms of aspirin, Vitamin C, Vitamin E, or ozone on fertility in female mice treated with PM2.5. METHODS: Eighty-four ICR mice were divided into six groups: control group, PM2.5group, PM2.5 + aspirin group, PM2.5 + Vitamin C group, PM2.5 + Vitamin E group, and PM2.5 + ozone group. PM2.5was given by intratracheal instillation every 2 days for 3 weeks. Aspirin, Vitamin C, and Vitamin E were given once a day by oral gavage for 3 weeks, and ozone was administered by intraperitoneal injection once a day for 3 weeks. The levels of anti-Müllerian hormone (AMH), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured using enzyme-linked immunosorbent assay. Western blotting analysis was used to analyze the expressions of Bcl-2, Bax, and caspase-3 in ovaries. Changes in histological structure were examined by light microscope and electron microscopy was used to detect ultramicrostructure. RESULTS: The results demonstrated that PM2.5 decreased AMH levels (P < 0.001); however, aspirin (P < 0.001), Vitamin C (P < 0.001), Vitamin E (P = 0.001), and ozone (P = 0.002) alleviated the decrease. Changes of IL-6, TNF-α, 8-OHdG, Bax/Bcl-2, and caspase-3 in PM2.5group were increased compared to control group (P < 0.001), while in PM2.5 + aspirin, PM2.5 + Vitamin C, PM2.5 + Vitamin E, and PM2.5 + ozone groups, they were statistically decreased compared to PM2.5group (P < 0.001 or P< 0.05). CONCLUSIONS: PM2.5cause the damage of ovaries, and aspirin, Vitamin C, Vitamin E, and ozone antagonizes the damage. The protective mechanism is probably due to its ability to blunt the inflammatory and oxidative stress caused by PM2.5, which subsequently suppressing the expression of apoptotic regulatory protein and reducing the incidence of ovary apoptosis.

Analgesic Effects and Neuropathology Changes of Electroacupuncture on Curing a Rat Model of Brachial Plexus Neuralgia Induced by Cobra Venom.

BACKGROUND: Electroacupuncture (EA) is widely applied to treat neuropathic pain. Brachial plexus neuralgia (BPN) is a common form of chronic persistent pain. Few studies have evaluated the analgesic effects and mechanism of EA using the novel animal model of BPN. OBJECTIVE: To observe the curative effects of repeated EA on curing BPN induced by administration of cobra venom to the lower trunk of the right brachial plexus. STUDY DESIGN: Controlled animal study. SETTING: Department of Anesthesiology, Pain Medicine & Critical Care Medicine, Aviation General Hospital of China Medical University. METHODS: Sixty-six adult male Sprague-Dawley rats were equally and randomly divided into the following groups: normal control (NC), brachial plexus neuralgia (BPN), BPN with sham EA stimulation, BPN with EA stimulation starting on postoperative day 1 (EA1), and BPN with EA stimulation starting on postoperative day 12 (EA12). The BPN model was established by administration of cobra venom to the lower trunk of the right brachial plexus. On postoperative day 1 or day 12, EA (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 - 1.5 - 2 mA) was applied to the right "Shousanli" (LI10) and "Quchi" (LI11) acupoints for 30 minutes, once every other day for 12 times in both groups. Mechanical withdrawal thresholds (MWT) were tested with von Frey filaments. Video recordings were conducted to analyze the spontaneous exploratory behaviors. Moreover, the organizational and structural alterations of the right brachial plexus and cervical cord (C8-T1) were examined via light and electron microscopy. RESULTS: Following the production of the BPN model, the MWT of both ipsilateral and contralateral paws demonstrated a profound decrease (P < 0.05). But after EA interventions, the MWT showed a significant increase (P < 0.05). In comparison to the EA12 group, the analgesic effects of the EA1 group were more significant, and similar results were observed in exploratory behaviors. However, grooming behaviors did not demonstrate significant differences. Meanwhile, on day 12 after surgery it was observed under light microscopy that the inflammatory response in the right brachial plexus and cervical cord (C8-T1) were significantly attenuated after EA stimulation. Furthermore, the demyelination of the brachial plexus and cervical cord (C8-T1) were also reversed. LIMITATIONS: Limitations include the fact that there was demyelination of the cervical cord (C8-T1) in the control group because of inappropriate manipulation. CONCLUSION: Repeated EA contributes significant analgesic effects in the treatment of BPN.

Trigeminal neuralgia induced by cobra venom in the rat leads to deficits in abilities of spatial learning and memory.

BACKGROUND: Patients with chronic pain usually suffer from cognitive impairment, with memory deterioration being the most common deficit that affects daily functioning and quality of life. The causes for this impairment are not clear despite intensive clinical studies. Few studies have evaluated impaired learning using animal models of persistent pain. OBJECTIVE: In this study, a new trigeminal neuralgia model induced by cobra venom was adopted to explore effects of chronic pain on spatial learning and memory in rats. STUDY DESIGN: Controlled animal study. SETTING: Department of Anesthesiology, Pain Medicine & Critical Care Medicine, Aviation General Hospital of China Medical University. METHODS: Thirty adult male Sprague-Dawley rats were randomly divided into 2 groups (n = 15): NS control group and cobra venom group, 0.9% sterile saline or cobra venom solution was injected into the sheath of the infraorbital nerve (ION), respectively. The development of trigeminal neuralgia was accessed by changes in free behavioral activity 3 days before the surgery and 3, 7, 12, 20, and 30 days after the surgery to identify whether the model was successful or not. Morris water maze test determined the abilities of spatial learning and memory at the time points before the surgery, and 2 weeks and 5 weeks after the surgery. We also observed the ultrastructure of the ION and medulla oblongata of rats following 8 weeks of chronic trigeminal neuropathic pain. RESULTS: Rats with the cobra venom injection displayed significantly more face grooming and fewer exploratory activities compared to the NS control group or baseline (P < 0.01). Both groups improved their latency to reach the platform with the largest difference on the first day (P < 0.01), but without memory deficits in a probe trial for the second water maze protocol. For the third water maze testing, the rats in the cobra venom group experienced decreased abilities of spatial learning and memory, a longer latency with spatial memory deficits during the probe trial (P < 0.05). At the ultrastructural level, we found changes in the medulla oblongata after cobra venom injection resulting in severe demyelination and loss of axons that might be implicated in the causes of cognitive deficits. LIMITATIONS: Limitations include partial vision loss in the eye on the lesion side of the rats that might be missed and the absence of evaluating the ultrastructural changes in other parts of the brain. CONCLUSIONS: The results of this study suggest that trigeminal neuralgia induced by cobra venom in adult rats can impair spatial learning and memory function over time and results in demonstrable changes in the ultrastructure of the medulla oblongata. This new animal model may be useful for future studies on the effect of chronic pain on learning and cognition.

Spine surgery may cause more spinal epidural hematomas than spinal puncture.

BACKGROUND: Spinal epidural hematoma (SEH) is a rare but acute and possibly devastating clinical event. The purpose of this study is to assess the multiple etiologies of SEH seen in an academic medical center over a 15-year span. We have examined the etiologies of SEH occurring in a single institution, the University of Pittsburgh Medical Center (UPMC) over the last fifteen years using an electronic record keeping system and database: the Medical Archive Retrieval System (MARS). METHODS: We screened MARS from 1986 - 2001 using key words: epidural, hematoma and spinal. All potential SEH cases were reviewed and only those confirmed by surgical intervention were identified as positive SEH and reported in this study. RESULTS: There were 17 cases of confirmed SEH. Among them, seven cases were from spontaneous bleeding, seven cases following spinal surgery, and three cases from traumatic spinal fracture. There were no findings of SEH that were related to spinal or epidural anesthesia. Among the seven patients with spontaneous SEH; two were receiving anti-coagulants for deep venous thrombosis (DVT) and had elevated prothrombin time (PT) and activated partial thromboplastine time (APTT), one had hemophilia (type B), four had hypertension, and three out of seven had chronic renal or liver disease. Among postoperative SEH patients, two of the seven patients were receiving chemotherapy and radiation therapy and one had ongoing hemodialysis for renal failure. Among three patients with traumatic SEH, two had ankylosing spondylitis. Six patients had a history of alcohol abuse. CONCLUSIONS: Spontaneous bleeding is by far the leading cause of SEH with spinal surgery being the second leading cause. Patients with multiple co-morbidities that result in coagulopathy from a variety of causes include liver or renal disease, alcohol abuse, radiation therapy, or chemotherapy. Neuraxial anesthesia is an extremely rare cause of SEH.

A new animal model of trigeminal neuralgia produced by administration of cobra venom to the infraorbital nerve in the rat.

BACKGROUND: Understanding the mechanism of trigeminal neuralgia may be elucidated by developing laboratory animal models that closely mimic the features of this specific type of neuropathic pain. We have developed an experimental animal model for trigeminal neuralgia using a technique of injecting cobra venom into the infraorbital nerve (ION) trunk. METHODS: Male Sprague-Dawley rats were subjected to the administration of cobra venom or saline into the ION trunk. Mechanical stimuli were applied to the ION territory in consecutive days after surgery. Mechanical thresholds were measured over a 90-day period on the bilateral facial region. Vascular permeability in the ION territory was measured using Evans blue dye. RESULTS: The cobra venom-treated rats developed mechanical allodynia 3 days after surgery that lasted for 60 days postoperatively at the ipsilateral side. The mechanical thresholds of the contralateral ION territory also showed a profound decrease but were sustained for only approximately 30 days. There was no change of mechanical thresholds in the control groups. The extravasation of Evans blue increased significantly in the skin after administration of cobra venom to the ION compared with control rats (P < 0.05). CONCLUSION: The cobra venom model may provide a reasonable model for investigating the mechanism of trigeminal neuropathic pain.

Intraoperative cardiac arrest during anesthesia: a retrospective study of 218,274 anesthetics undergoing non-cardiac surgery.

BACKGROUND: Patient safety has been gained much more attention in recent years. The authors reviewed patients who had cardiac arrest in the operating rooms undergoing noncardiac surgery between January 1989 and December 2001 at the University of Pittsburgh Medical Center, USA. The main objectives of the study were to determine the incidence of intraoperative cardiac arrest, to identify possible causes of cardiac arrest and to explore amenable modifications. METHODS: With approval by the University of Pittsburgh Institutional Review Board, patients experienced cardiac arrest during surgery were retrieved from medical records, surgical operation and anesthesia records and pathological reports by searching the Medical Archival Retrieval System (MARS), a hospital electronic searching system. Cases of cardiac arrest were collected over a period of thirteen years from the Presbyterian University Hospital (PUH), USA. RESULTS: We found 23 cases of intraoperative cardiac arrests occurred in 218 274 anesthesia cases (1.1 per 10 000). Fourteen patients (60.8%) died in the operating room, leading to a mortality rate from all causes of 0.64 per 10 000 anesthetics. Immediate overall survival rate after arrest was 39% (9/23). Half of the patients (12/23) were emergency cases with 41% survival rate (5/12). One fourth of the arrests were trauma patients (6/23). Most arrest patients (87%, 20/23) were American Society of Anesthesiologists Physical Status (ASA PS) IV and V, while only three patients were ASA PS-I, II and III, respectively. One case was attributable to an anesthesia-related cardiac arrest and recovered after successful resuscitation. CONCLUSIONS: Most intraoperative cardiac arrests were not due to anesthesia-related causes. Anesthesia-related cardiac arrests might have a higher survival rate when compared to other possible causes of cardiac arrest in the operating room.

Screening of differentially expressed genes in the hypothalamus of a rat neuropathic pain model following sciatic nerve injury.

BACKGROUND: Neuropathic pain is induced by injury or disease of the nervous system. Most studies have so far focused only on a few known molecules and signaling pathways among neurons. However, all signal transmissions involved in neuropathic pain appear to be an integral system at different molecular levels. This study was designed to screen the differentially expressed genes of the hypothalamus in chronic constriction injury (CCI) rats and analyze their functions in developing neuropathic pain. METHODS: Ten adult female Sprague-Dawley rats ((200 +/- 10) g) were used in experimental group and sham group (n = 5 in each group). Mechanical allodynia tests were performed to ensure that the CCI rat model was constructed successfully. Total hypothalamus RNAs were isolated from each group. Forward suppression subtractive hybridization (SSH) library of rat hypothalamus was constructed and up-regulated cDNA clones at neuropathic pain states were obtained via suppressed subtractive hybridization technique and the functions of these genes were analyzed bioinformatically. RESULTS: Mechanical allodynia tests showed that the experimental rats had a significantly reduced mechanical allodynia threshold 3 to 13 days after CCI vs sham surgery rats (P < 0.01), indicating that the model was successful. Forward SSH library of the rat hypothalamus was constructed successfully and 26 over-expressed expression sequence tags (ESTs) were obtained from these up-regulated cDNA clones. CONCLUSION: Twenty-six up-regulated genes, involved in the regulation of cell cycle and apoptosis, signal transduction, and neuroprotection, may play key roles in decreasing mechanical withdraw thresholds in CCI rats, which implicates a multidimensional and integrated molecular mechanism at gene level in developing neuropathic pain with the supraspinal contributions.