OBJECTIVE: To explore the relationship between serum sodium level and the risk of delirium in patients with sepsis. METHODS: Based on the Medical Information Mart for Intensive Care-IV (MIMIC-IV), adult patients with sepsis in the intensive care unit (ICU) were enrolled. The serum sodium level prior to the onset of sepsis during hospitalization was used as the exposure variable. Delirium was assessed using the ICU-confusion assessment method (ICU-CAM) as the primary outcome. Patients were divided into delirium and non-delirium groups based on the occurrence of delirium. The relationship between serum sodium level and delirium risk was described using restricted cubic spline (RCS) to determine the optimal reference range for serum sodium. Logistic regression analysis was used to evaluate the effect of blood sodium levels on delirium in sepsis patients. Subgroup analyses were performed to explore potential interactions and further validate the robustness of the results. Receiver operator characteristic curve (ROC curve) analysis was performed to assess the predictive value of serum sodium level for delirium occurrence in patients with sepsis. RESULTS: A total of 13 889 patients with sepsis were included, of which 4 831 experienced delirium. The maximum and mean serum sodium values were significantly higher in the delirium group compared to the non-delirium group, while there were no statistically significant differences in terms of initial and minimum serum sodium values between the two groups. Compared with the non-delirium group, the delirium group had a higher mortality and longer hospital stay. The RCS curve showed that a "U"-shaped relationship between serum sodium level and delirium risk in patients with sepsis, with the optimal reference range for average serum sodium was 135.3-141.3 mmol/L. Group based on this reference range, compared to the group with 135.3 mmol/L ≤ serum sodium ≤ 141.3 mmol/L, the delirium incidence and mortality were significantly higher, and the hospital stay was longer in the groups with serum sodium < 135.3 mmol/L and serum sodium ≥ 141.3 mmol/L [delirium incidence: 36.92%, 40.88% vs. 31.22%; 28-day mortality: 23.08%, 20.15% vs. 13.39%; 90-day mortality: 30.75%, 24.81% vs. 18.26%; in-hospital mortality: 19.53%, 17.48% vs. 11.61%; ICU mortality: 14.35%, 14.05% vs. 9.00%; hospital length of stay (days): 10.1 (6.1, 17.7), 9.4 (5.4, 17.0) vs. 8.9 (5.5, 15.4), length of ICU stay (days): 3.7 (2.1, 7.1), 4.0 (2.1, 8.9) vs. 3.2 (1.9, 6.8); all P < 0.01]. Logistic regression analysis showed that, in the initial model and each factor-adjusted models, compared to the reference group with 135.3 mmol/L ≤ serum sodium < 141.3 mmol/L, serum sodium < 135.3 mmol/L increased the risk of delirium in septic patients by 21% to 29% [odds ratio (OR) was 1.21-1.29, all P < 0.01], while serum sodium ≥ 141.3 mmol/L increased the delirium risk by 28%-52% (OR was 1.28-1.52, all P < 0.01). Subgroup analyses based on gender, age, race, diuretic use, and sequential organ failure assessment (SOFA) score revealed there was no significant interactions between subgroup variables and serum sodium, and the results supported that both serum sodium < 135.3 mmol/L and serum sodium ≥ 141.3 mmol/L were risk factors for delirium in septic patients. ROC curve analysis showed that the area under the curve (AUC) for predicting delirium in septic patients based on serum sodium was 0.614, with a cut-off value of 139.5 mmol/L yielding a specificity of 67.5% and sensitivity of 50.9%. CONCLUSIONS The risk of delirium in patients with sepsis is associated with serum sodium level in a "U"-shaped manner. Both high and low serum sodium levels are associated with increased risk of delirium, higher all-cause mortality, and prolonged hospital stays in patients with sepsis. Abnormal serum sodium levels may have predictive value for sepsis-associated delirium and could serve as an early biomarker for identifying delirium in septic patients, although further validation is needed.
Humans ; Delirium/etiology* ; Sepsis/complications* ; Sodium/blood* ; Intensive Care Units ; Risk Factors ; Male ; Middle Aged ; Female ; Aged ; Logistic Models ; Adult

Objective:To evaluate the effect of losartan on acute kidney injury (AKI) and the relationship with mitochondrial fusion-fission in septic mice.Methods:One hundred and twenty-eight SPF male C57BL/6J mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=32 each) using a random number table method: sham operation group (Sham group), sham operation+ losartan group (Sham+ LOS group), sepsis-associated AKI group (SA-AKI group), and sepsis-associated AKI+ losartan group (SA-AKI+ LOS group). Sepsis was induced by cecal ligation and puncture in anesthetized mice. Sham+ LOS group and SA-AKI+ LOS group received intraperitoneal injection of losartan 5 mg/kg, once a day, for 3 consecutive days, starting from 3 days before sham operation or developing the model. The equal volume of solvent was given instead in Sham group and SA-AKI group. Twenty mice were randomly selected to observe the survival 7 days after surgery. At 24 h after sham operation or establishing the model, serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations were determined by the colorimetric method, and serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and high-mobility group box 1 protein (HMGB1) were measured using enzyme-linked immunosorbent assay. Renal tissues were obtained for microscopic examination of pathological changes which were scored and for determination of mitochondrial membrane potential (using JC-1 method) and expression of dynamin-related protein 1 (Drp1) and mitofusin-2 (Mfn2) (using Western blot). Results:Compared with Sham group, the survival rate was significantly decreased, the serum BUN, Cr, TNF-α, IL-6 and HMGB1 concentrations and renal tubular injury score were increased, the ATP content and MMP were decreased, the expression of Drp1 was up-regulated, the expression of Mfn2 was down-regulated ( P<0.05), and pathological changes were found in renal tissues in SA-AKI group and SA-AKI+ LOS group. Compared with SA-AKI group, the survival rate was significantly increased, serum concentrations of BUN, Cr, TNF-α, IL-6 and HMGB1 and renal tubular injury score were decreased, the ATP content and MMP were increased, the expression of Drp1 was down-regulated, the expression of Mfn2 was up-regulated ( P<0.05), and the pathological changes of renal tissues were significantly attenuated in SA-AKI+ LOS group. Conclusions:Losartan can alleviate AKI in septic mice, and the mechanism may be related to promoting mitochondrial fusion and inhibiting mitochondrial fission.

Objective:To investigate and analysis of the occurrence and influencing factors of sarcopenia in elderly critically ill patients in the intensive care unit (ICU).Methods:A prospective cohort study was conducted. Elderly patients (aged ≥ 60 years) admitted to the ICU of Tianjin Medical University General Hospital from November 2023 to June 2024 were enrolled. Clinical records were collected, and conduct muscle mass and strength measurements, as well as upper arm circumference and calf circumference were measured. Appendicular skeletal muscle index (ASMI) of less than 7.0 kg/m 2 for males and less than 5.7 kg/m 2 for females was defined as reduced muscle mass, grip strength of less than 28 kg for males and less than 18 kg for females was defined as decreased muscle strength, patients meeting both low muscle mass and low muscle strength criteria were diagnosed with sarcopenia. According to the diagnostic criteria for sarcopenia, patients were divided into sarcopenia group and non-sarcopenia group. Multivariate Logistic regression analysis was applied to identify risk factors for sarcopenia in the elderly and to develop a predictive model for the occurrence of sarcopenia. The predictive value of various risk factors for sarcopenia in elderly critically ill patients were evaluated by receiver operator characteristic curve (ROC curve). The Kaplan-Meier curve for the length of ICU stay of two groups patients were drawn. Results:Finally, 540 elderly critically ill patients were included, including 43 patients with sarcopenia, and the incidence of sarcopenia was 8.0%. Univariate analysis showed that there were significantly differences in body mass index (BMI), number of hospitalizations in the past year, the length of ICU stay, ventilation mode, duration of mechanical ventilation, pre-admission exercise habits, nutritional support methods, upper arm circumference, calf circumference, and albumin infusion between the sarcopenia group and the non-sarcopenia group. Multivariate Logistic regression analysis showed that BMI [odds ratio ( OR) = 0.79, 95% confidence interval (95% CI) was 0.67-0.93, P = 0.004], calf circumference ( OR = 0.64, 95% CI was 0.54-0.76, P < 0.001), and duration of mechanical ventilation ( OR = 1.06, 95% CI was 1.01-1.12, P = 0.034) were associated with an increased risk of sarcopenia in elderly critically ill patients. The ROC curve results showed that the area under the curve (AUC) and 95% CI of BMI, calf circumference, and duration of mechanical ventilation for predicting sarcopenia in elderly critically ill patients were 0.828 (0.767-0.888), 0.889 (0.844-0.933), and 0.397 (0.299-0.496), respectively, with cut-off values of 22.95 kg/m 2, 28.25 cm, and 50.50 days, respectively. The Kaplan-Meier curve showed that the cumulative survival rate of patients with sarcopenia was significantly lower than that of the non-sarcopenia group (Log-Rank test: χ 2 = 5.619, P = 0.018). Conclusion:Lower BMI, smaller calf circumference, and longer duration of mechanical ventilation are associated with an increased risk of sarcopenia in critically ill elderly patients.

Objective:To compare the efficacy of closed-loop target-controlled deep versus moderate neuromuscular blockade in gynecological laparoscopic surgery.Methods:This was a prospective study. Fifty American Society of Anesthesiologists Physical Status classification I or Ⅱ patients, aged 18-64 yr, with body mass index of 18-30 kg/m 2, scheduled for elective gynecological laparoscopic surgery in the General Hospital of Tianjin Medical University from March 2020 to March 2021, were allocated into 2 groups ( n=25 each) using a random number table method: closed-loop target-controlled moderate neuromuscular blockade group (group TOF) and closed-loop target-controlled deep neuromuscular blockade group (group PTC). Rocuronium was given by closed-loop target-controlled infusion in both groups. In group TOF, the target muscle relaxation was considered as train-of-four stimulation (TOF) of 1 or 2. In group PTC, the target muscle relaxation was considered as post-titanic count of 1 or 2. The score for operator′s satisfaction with muscle relaxation, grading, satisfaction rate, mean pneumo-peritoneum pressure, consumption of rocuronium, recovery index, recovery time to a TOF ratio 0.9 and time to extubation were recorded. The postoperative visual analogue scale score for abdominal pain and use of rescue analgesics were recorded, and the occurrence of complications such as shoulder pain, arm pain, nausea, vomiting and hypoxemia was also recorded within 48 h after surgery. Results:Compared with group TOF, the score for operator′s satisfaction with muscle relaxation, grading and satisfaction rate were significantly increased, the mean pneumo-peritoneum pressure was decreased, the total and average consumption of rocuronium was increased, the recovery time of a TOF ratio 0.9 was prolonged, and the postoperative visual analogue scale score for abdominal pain and usage rate of flurbiprofenate were decreased in group PTC ( P<0.05). There were no significant differences in the recovery index, tracheal extubation time or postoperative incidence of hypoxemia, shoulder pain, arm pain and nausea and vomiting between the two groups ( P>0.05). Conclusions:Compared with the closed-loop target-controlled moderate neuromuscular blockade, the closed-loop target-controlled deep neuromuscular blockade provides more satisfactory surgical conditions for gynecological laparoscopic surgery, decreases pneumoperitoneum pressure and reduces related complications, without increasing the development of postoperative adverse reactions.

Objective:To evaluate the role of the autophagy in hydrogen-induced reduction of myocardial injury in septic mice.Methods:A total of 192 clean-grade healthy male C57BL/6J mice, aged 6-8 weeks, weighing 20-25 g, were divided into 6 groups ( n=32 each) using a random number table method: sham operation group (group Sham), sham operation plus hydrogen group (group Sham+ H 2), sepsis group (group S), sepsis plus hydrogen group (group S+ H 2), sepsis plus bafilomycin A1 group (group S+ BafA1) and sepsis plus hydrogen plus bafilomycin A1 group (group S+ H 2+ BafA1). Sepsis was produced by cecal ligation and puncture (CLP) after anesthesia. The mice inhaled 2% hydrogen for 1 h starting from 1 and 6 h after operation in group Sham+ H 2, group S+ H 2 and group S+ H 2+ BafA1. Bafilomycin A1 1 mg/kg was intraperitoneally injected at 1 h after operation in S+ BafA1 and S+ H 2+ BafA1 groups. Twenty mice in each group were selected to record the 7-day survival rates after operation. Then the mice were sacrificed at 24 h after operation to observe the pathological changes of myocardial tissues which were scored and detect the serum cardiac troponin I (cTnI) concentration (by enzyme-linked immunosorbent assay) and determine the level of microtubule-associated protein 1 light chain 3 B (LC3B) and P62 (by Western blot). LC3Ⅱ/LC3Ⅰratio was calculated. Results:Compared with group Sham, the 7-day survival rate after operation was significantly decreased, the serum cTnI concentrations and pathological scores of myocardial tissues were increased, the expression of P62 was up-regulated ( P<0.05), no significant change was found in LC3Ⅱ/LC3Ⅰratio ( P>0.05), and no significant change was found in the parameters mentioned above in group Sham+ H 2 ( P>0.05). Compared with group S, the 7-day survival rate after operation was significantly increased, the serum cTnI concentrations and pathological scores of myocardial tissues were decreased, LC3Ⅱ/LC3Ⅰratio was increased, and the expression of P62 was down-regulated in group S+ H 2, and LC3Ⅱ/LC3Ⅰratio was significantly decreased, and the expression of P62 was up-regulated in group S+ BafA1 ( P<0.05). Compared with group S+ H 2, the 7-day survival rate was significantly decreased, the serum cTnI concentrations and pathological scores of myocardial tissues were increased, LC3Ⅱ/LC3Ⅰratio was decreased, and the expression of P62 was up-regulated in group Sham+ H 2 ( P<0.05). Conclusions:The mechanism by which hydrogen alleviates myocardial damage may be related to promoting autophagy in septic mice.

Objective:To evaluate the effects of inhaling high concentration hydrogen on myocardial injury and mitochondrial biogenesis in septic mice.Methods:One hundred and twenty-eight clean-grade healthy male C57BL/6J mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=32 each) using a random number table method: sham operation group (group Sham), sham operation + hydrogen group (group Sham+ H), sepsis group (group Sep), and sepsis+ hydrogen group (group Sep+ H). The sepsis model was developed by cecal ligation and puncture in anesthetized animals. In Sham+ H and Sep+ H groups, 67% H 2 was inhaled for 1 h starting from 1 and 6 h after operation, respectively. Twenty mice in each group were randomly selected to observe the survival conditions at 7 days after operation. Blood samples were taken from the remaining mice at 24 h after operation for determination of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), cardiac troponin I (cTnI) and creatine kinase isoenzyme (CK-MB) (by enzyme-linked immunosorbent assay), for examination of the pathological changes of myocardial tissues (by HE staining), and for determination of the mitochondrial membrane potential (MMP) (by fluorescence spectrophotometry), ATP content (by luciferase assay), and expression of myocardial peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), nuclear respiratory factor 2 (NRF2) and mitochondrial transcription factor A (TFAM) (by Western blot). Results:Compared with Sham group, the survival rate was significantly decreased, the serum concentrations of TNF-α, IL-1β, cTnI and CK-MB and pathological score were increased, the MMP and content of ATP in myocardial mitochondria were decreased, and the expression of PGC-1α, NRF2 and TFAM in myocardial tissues was down-regulated in Sep group ( P<0.05), and no significant change was found in the parameters mentioned above in Sham+ H group ( P>0.05). Compared with group Sep, the survival rate was significantly increased, the serum concentrations of TNF-α, IL-1β, cTnI and CK-MB and pathological score were decreased, the MMP and content of ATP in myocardial mitochondria were increased, and the expression of PGC-1α, NRF2 and TFAM in myocardial tissues was up-regulated in group Sep+ H ( P<0.05). Conclusions:Inhaling high concentration hydrogen can attenuate sepsis-induced myocardial injury in mice, and the mechanism may be related to promotion of mitochondrial biosynthesis and improvement in mitochondrial function.

Objective:To evaluate the effects of inhalation of high-concentration hydrogen on acute kidney injury (AKI) and mitochondrial dynamics in septic mice.Methods:One hundred and twenty-eight male C57BL/6J mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=32 each) using a random number table method: sham operation group (group Sham), sham operation + hydrogen group (group Sham+ H), sepsis AKI group, and sepsis AKI+ hydrogen group (group S-AKI+ H). A mouse model of sepsis-induced AKI was developed by cecal ligation and puncture in anesthetized animals. In Sham+ H and S-AKI+ H groups, 67% H 2+ 33% O 2 was inhaled for 1 h starting from 1 and 6 h after sham operation or developing the model, respectively. Twenty mice were selected to observe the survival at 7 days after developing the model. At 24 h after developing the model, blood samples were collected for determination of serum BUN and Cr concentrations (by colorimetric analysis), and renal tissues were obtained for determination of the contents of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and high mobility group protein B1 (HMGB1) (by enzyme-linked immunosorbent assay), activities of superoxide dismutase (SOD) and catalase (CAT) (by spectrophotometry) and expression of dynamin-related protein 1 (Drp1) and mitofusin 2 (Mfn2) (by Western blot). The damage to the renal tubules was scored after HE staining. Results:Compared with Sham group, the survival rate was significantly decreased, the serum BUN and Cr concentrations, renal tubular damage score and contents of TNF-α, IL-1β and HMGB1 were increased, the activities of SOD and CAT were decreased, the expression of Drp1 was up-regulated, and the expression of Mfn2 was down-regulated in S-AKI group ( P<0.05), and no significant change was found in the parameters mentioned above in Sham+ H group ( P>0.05). Compared with S-AKI group, the survival rate was significantly increased, the serum BUN and Cr concentrations, renal tubular injury score and contents of TNF-α, IL-1β and HMGB1 were decreased, the activities of SOD and CAT were increased, the expression of Drp1 was down-regulated, and the expression of Mfn2 was up-regulated in S-AKI+ H group ( P<0.05). Conclusions:Inhalation of high-concentration hydrogen can alleviate AKI in septic mice, and the mechanism may be related to inhibition of renal mitochondrial fission and promotion of mitochondrial fusion.

Objective:To evaluate the effect of high concentration hydrogen on myocardial injury and expression of mammalian STE20-like protein kinases 1 (Mst1) in septic mice.Methods:One hundred and five clean-grade healthy male C57BL/6J mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=35 each) using a random number table method: sham operation group (group Sham), sepsis group (group SEP), and sepsis+ high concentration hydrogen group (group SEP+ HCH). The model of sepsis-induced myocardial injury was developed by cecal ligation and perforation in anesthetized mice. In SEP+ HCH group, high concentration hydrogen (66.7%) was inhaled for 1 h starting from 1 and 6 h after the successful preparation of the model. Twenty mice were taken from each group to observe the survival rate at day 7 after operation. Blood samples from the medial canthus were collected after deep anesthesia at 24 h after surgery for determination of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) concentrations (by enzyme-linked immunosorbent assay). Then the animals were sacrificed, and the heart tissues were taken for examination of the pathological results (with a light microscope) which were scored and for determination of apoptosis in myocardial cells (by TUNEL) and expression of Mst1, dynamic-related protein 1 (Drp1) and mitofusin 2 (Mfn2) in myocardium (by Western blot). Results:Compared with group Sham, the survival rate at 7 days after operation, pathological score, apoptosis index and concentrations of TNF-α and IL-6 were significantly increased, Mst1 and Drp1 expression was up-regulated, and Mfn2 expression was down-regulated in group SEP ( P<0.05). Compared with group SEP, the survival rate at 7 days after operation, pathological score, apoptosis index and concentrations of TNF-α and IL-6 were significantly decreased, Mst1 and Drp1 expression was down-regulated, and Mfn2 expression was up-regulated in group SEP+ HCH ( P<0.05). Conclusions:Inhalation of high-concentration hydrogen can attenuate the myocardial injury in septic mice, and the mechanism may be related to down-regulation of Mst1 expression, improvement in mitochondrial dynamics, and inhibition of apoptosis in myocardial cells.

Objective:To evaluate the relationship between B-cell lymphoma/adenovirus E1B19 kDa-interacting protein 3-like protein (BNIP3L)/adenovirus E1B-interacting protein and mitochondrial dysfunction in the hippocampus of mice with sepsis-associated encephalopathy (SAE).Methods:One hundred and eighty C57BL/6J mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=45 each) using a random number table method: control group (C group), sham operation group (Sham group), SAE group, and SAE+ BNIP3L agonist carfilzomib group (SC group). The sepsis model was developed by cecal ligation and puncture (CLP) in anesthetized animals. In SC group, carfilzomib 2 mg/kg was intraperitoneally injected at 2 h after CLP. Twenty mice in each group were selected, and the survival at 7 days after operation was recorded. Eight surviving mice in each group were selected at 1 week after CLP for Morris water maze test. The remaining mice were sacrificed at 24 h after surgery, and the hippocampal tissues were harvested for determination of the expression of BNIP3L (by immunofluorescence) and BNIP3L in mitochondrial protein (by Western blot) and for microscopic examination of the morphological structure of mitochondria. The mitochondrial ATP content was measured by fluorescein-fluorescence enzyme luminescence method, and the mitochondrial membrane potential (MMP) was measured by fluorescence spectrophotometry. Results:Compared with C and Sham groups, the survival rate was significantly decreased, the escape latency was prolonged, the time of staying at the original platform quadrant was shortened, and the number of crossing the original platform region was decreased, the expression of BNIP3L in the hippocampal mitochondria was down-regulated, the MMP and content of mitochondrial ATP were decreased ( P<0.05), the intensity of fluorescence of BNIP3L in the hippocampus was decreased, and the damage to mitochondrial ultrastructure was marked in SAE group. Compared with SAE group, the survival rate was significantly increased, the escape latency was shortened, the time of staying at the original platform quadrant was prolonged, and the number of crossing the original platform region was increased, the expression of BNIP3L in the hippocampal mitochondria was up-regulated, the MMP and content of mitochondrial ATP were increased ( P<0.05), the intensity of fluorescence of BNIP3L in the hippocampus was decreased, and the damage to mitochondrial ultrastructure was attenuated in SC group. Conclusions:BNIP3L-mediated mitochondrial dysfunction may be involved in the mechanism of SAE developed in mice.

Objective:To evaluate the effect of sleep fragmentation on postoperative cognitive dysfunction (POCD) and hippocampal glutaminergic metabolism in aged mice anesthetized with isoflurane.Methods:Forty healthy SPF-grade male C57BL/6J mice, aged 18 months, weighing 20-30 g, were divided into 4 groups ( n= 10 each) by the random number table method: normal control group (group C), sleep fragmentation group (group SF), isoflurane anesthesia/surgery group (group I/S), and sleep fragmentation plus isoflurane anesthesia/surgery group (group SF+ I/S). Group C did not received any treatment. Group SF received sleep fragmentation for 24 h. The right carotid artery exposure was performed under isoflurane anesthesia in group I/S. Group SF+ I/S received isoflurane anesthesia/right carotid artery exposure at 24 h after sleep fragmentation. The metabolic levels of glutamate (Glu), glutamine (Gln), Glu/Gln complex (Glx), and N-acetylaspartate (NAA) and their ratio to creatine (Cr) were measured by in vivo 9.4T hydrogen proton magnetic resonance spectroscopy at 2 h after anaesthesia. Y maze and Morris water maze tests were used to evaluate the cognitive function at 1-7 days after surgery. The mice were sacrificed after the behavioral testing, brain tissues were immediately obtained, and the number of Nissl bodies and density of dendritic spines in the hippocampal CA1 region were measured by Nissl staining and Golgi staining, respectively. Results:Compared with group C, the percentage of exploration time and shuttle times at the novel arm were significantly decreased, the number of crossing the original platform was decreased, the time of stay at the target quadrant was shortened, the ratios of Glu/Cr, Gln/Cr and Glx/Cr in the hippocampal CA1 region were increased, and the ratio of NAA/Cr was decreased, and the number of Nissl bodies and density of dendritic spines were decreased in SF, I/S and SF+ I/S groups ( P<0.05). Compared with group SF and group I/S, the percentage of exploration time and shuttle times at the novel arm were significantly decreased, the number of crossing the original platform was decreased, the time of stay at the target quadrant was shortened, the ratios of Glu/Cr and Glx/Cr in hippocampal CA1 region was increased, the ratio of NAA/Cr was decreased, and the number of Nissl bodies and density of dendritic spines were decreased in group SF+ I/S ( P<0.05). Conclusions:Sleep fragmentation exacerbates POCD in aged mice anesthetized with isoflurane, and the mechanism is related to nerve injury induced by abnormality in hippocampal glutaminergic metabolism excitability.