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Memory impairment is one of the main characteristics of postoperative cognitive dysfunction. It remains elusive how postoperative pathological changes of the brain link to the memory impairment. The clinical setting of perioperation was mimicked via partial hepatectomy under sevoflurane anaesthesia together with preoperative restraint stress (Hep‐Sev‐stress) in mice. Memory changes were assessed with fear conditioning. The medial prefrontal cortex (mPFC)‐dorsal hippocampus connectivity was evaluated with injecting neurotracer 28 days before surgery. Astrocytic activation was limited via injecting AAV‐GFAP‐hM4Di‐eGFP into the mPFC. Astrocytic and microglial phagocytosis of synapses were visualised with co‐labelling hippocampal neuronal axon terminals with PSD‐95 and S100β or Iba1. Neuroinflammation and oxidative stress status were also detected. Hep‐Sev‐stress impaired the memory consolidation (mean [standard error], 49.91 [2.55]% vs. 35.40 [3.97]% in the contextual memory, p = 0.007; 40.72 [2.78]% vs. 27.77 [2.22]% in cued memory, p = 0.002) and the cued memory retrieval (39.00 [3.08]% vs. 24.11 [2.06]%, p = 0.001) in mice when compared with these in the naïve controls. Hep‐Sev‐stress damaged the connectivity from the dorsal hippocampus to mPFC but not from the mPFC to the dorsal hippocampus and increased the astrocytic but not microglial phagocytosis of hippocampal neuronal axon terminals in the mPFC. The intervention also induced neuroinflammation and oxidative stress in the dorsal hippocampus and the mPFC in a regional‐dependent manner. Limiting astrocyte activation in the mPFC alleviated memory consolidation impairment induced by Hep‐Sev‐stress. Postoperative memory consolidation was impaired due to astrocytic phagocytosis‐induced connectivity injury from the dorsal hippocampus to the medial prefrontal cortex. [ABSTRACT FROM AUTHOR]

Malfunction of neutrophil apoptosis and elevated serum lactate levels are the key cellular mechanism of immune suppressive status in septic patients. However, whether increased lactate affects apoptosis of neutrophils and aggravates sepsis development, and the molecular mechanism remain unknown. In this study, first, we analyzed the transcriptional profiles of blood cells in sepsis patients (n = 39) and healthy volunteers (n = 40) to reveal that there is close correlation between the lactate‐related gene expression changes associated with lactate production and immune function in leukocytes, especially in neutrophils. Further, we explored the close relationship between lactate and delayed neutrophil apoptosis in human neutrophils. Programmed cell death 1 legand (PD‐L1) was highly expressed in septic patients compared with healthy volunteers. Then, we indicated that elevated levels of lactate in human neutrophils decreased neutrophil apoptosis (P <.001) by upregulating PD‐L1 expression. Inhibition of monocarboxylate transporter 1 (MCT1) significantly attenuated neutrophil apoptosis caused by lactate (P <.001). We further performed in vivo experiments in sepsis mice model and determined that increased lactate decreased neutrophil apoptosis (P <.05) and reduces mice survival rate (P <.001), which could also be rescued by MCT1 inhibitor (P <.05). This study revealed that elevated level of lactate in sepsis upregulates PD‐L1 expression to decrease apoptosis through MCT1 in neutrophils, which provides new insight into sepsis treatment strategy by reducing lactate accumulation. [ABSTRACT FROM AUTHOR]

Aims To explore the association between plasma concentrations of brain-derived neurotrophic factor (BDNF) and the occurrence of emergence agitation (EA) in the elderly after gastrointestinal surgery. Methods Seventy-two patients were recruited, who received gastrointestinal surgery and general anesthesia. BDNF level of blood was detected by ELISA before anesthesia (baseline), 10 min after tracheal intubation before the start of surgery, at skin closure, 10 min after tracheal extubation, and 24 h postoperatively. Patients with a Ricker Sedation-Agitation Scale (RSAS) score [greater than or equal to]5 at any time in the post anesthesia care unit were considered to have emergence agitation. Results The incidence of EA in this population was 40 % (29/72). The EA group had higher plasma BDNF levels at skin closure (497.86 ± 69.65 vs. 307.86 ± 51.91, p < 0.05) and especially at 10 min after tracheal extubation (900 ± 224.6 vs. 476.28 ± 107.15, p < 0.001). Moreover, the levels of plasma BDNF at skin closure, 10 min after tracheal extubation and postoperative pain, were positively related with RSAS scores. Conclusions Our results suggest that plasma BDNF is associated with the occurrence of emergence agitation after gastrointestinal surgery., Author(s): Xi Mei[sup.1] , Jianbin Tong[sup.1] Author Affiliations: (1) Department of Anesthesiology, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Yuelu District, 410013, Changsha, HunanChina Introduction Emergence [...]

Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron degeneration, which ultimately leads to paralysis and death. Mutation of TAR DNA binding protein 43 (TDP-43) has been linked to the development of an inherited form of ALS. Existing TDP-43 transgenic animals develop a limited loss of motor neurons and therefore do not faithfully reproduce the core phenotype of ALS. Here, we report the creation of multiple lines of transgenic rats in which expression of ALS-associated mutant human TDP-43 is restricted to either motor neurons or other types of neurons and skeletal muscle and can be switched on and off. All of these rats developed progressive paralysis reminiscent of ALS when the transgene was switched on. Rats expressing mutant TDP-43 in motor neurons alone lost more spinal motor neurons than rats expressing the disease gene in varying neurons and muscle cells, although these rats all developed remarkable denervation atrophy of skeletal muscles. Intriguingly, progression of the disease was halted after transgene expression was switched off; in rats with limited loss of motor neurons, we observed a dramatic recovery of motor function, but in rats with profound loss of motor neurons, we only observed a moderate recovery of motor function. Our finding suggests that mutant TDP-43 in motor neurons is sufficient to promote the onset and progression of ALS and that motor neuron degeneration is partially reversible, at least in mutant TDP-43 transgenic rats., Introduction Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of motor neurons and denervation atrophy of skeletal muscles. The disease inexorably progresses to paralysis and to death, often within [...]