UNASSIGNED: To review how anecdote and narrative medicine, primary cohort studies, epidemiological studies, and the dementia literature can be bridged to understand long-term postoperative cognitive decline.
UNASSIGNED: Primary cohort studies have measured recoverable declines in memory and executive function after major surgery, but less-appreciated sources also offer critical insights. Anecdote reveals that functionally-impactful cognitive decline may persist after physical recovery in some patients despite modern medications and monitoring, and that physicians are unprepared to address patients\' cognitive concerns. However, epidemiological studies reproducibly demonstrate that elective surgery has no, or a negligible, average impact on cognition in older patients. Cognitively provocative factors - like medical hospital admissions or health factors like diabetes and smoking - are common in late life, and surgery likely contributes minimally to long-term cognitive change for most patients.
UNASSIGNED: Patients should be reassured that, while anecdotes of durable cognitive change after surgery are easily accessible, most patients experience cognitive recovery after major surgery. However, those who do not recover deserve characterization of their symptoms and investigation of modifiable causes to facilitate cognitive recovery.

Postoperative cognitive dysfunction (POCD) is a kind of serious postoperative complication in surgery with general anesthesia and it may affect patients\' normal lives. Activated microglia are thought to be one of the key factors in the regulation of POCD process. Once activated, resident microglia change their phenotype and secrete kinds of cytokines to regulate inflammatory response in tissues. Among these secretory factors, brain-derived neurotrophic factor (BDNF) is considered to be able to inhibit inflammation response and protect nervous system. Therefore, the enhancement of BDNF expression derived from resident microglia is suggested to be potential treatment for POCD. In our study, we focused on the role of C8-ceramide (a kind of interventional drug) and assessed its regulatory effect on improving the expression of BDNF secreted from microglia to treat POCD. According to the results of our study, we observed that C8-ceramide stimulated primary microglia to up-regulate the expression of BDNF mRNA after being treated with lipopolysaccharide (LPS) in vitro. We proved that C8-ceramide had ability to effectively improve POCD of mice after being accepted carotid artery exposure and their abnormal behavior recovered better than that of mice from the surgery group. Furthermore, we also demonstrated that C8-ceramide enhanced the cognitive function of mice via the PKCδ/NF-κB signaling pathway. In general, our study has confirmed a potential molecular mechanism that led to the occurrence of POCD caused by surgery and provided a new clinical strategy to treat POCD.

Postoperative cognitive dysfunction (POCD) is a common postoperative complication in elderly patients. Liraglutide (LRG) has high homology (97%) with natural glucagon like peptide-1, and it has been proved to be effective in some nervous system diseases. Whether LRG could regulate POCD has not been reported.
Sevoflurane (Sev) was used to simulate postoperative cognitive dysfunction (POCD) model. Morris water maze test was performed to evaluate the memory ability and neurological function of rats. Escape latency, swim distance, crossing platform times, average velocity, and targeting quadrant time were analyzed. The cell apoptosis, mRNA and protein expression were measured through flow cytometry, PCR, and western blotting, respectively.
LRG significantly improved the memory ability and neurological function of Sev-treated rats, but 3-MA reversed the effects of LRG. LRG remarkably inhibited apoptosis but up-regulated autophagy related proteins both in vivo and in vitro levels. However, knocking down AMPK could markedly reverse the influence of LRG on apoptosis, autophagy, and cell apoptosis.
LRG induced autophagy activation can maintain cell homeostasis and promote cell survival by blocking the apoptotic pathway. LRG could improve Sev-induced POCD via activating autophagy, inhibiting apoptosis, and regulating AMPK/mTOR signaling pathway. This study provides a novel therapeutic strategy for the prevention and treatment of POCD.

Postoperative cognitive dysfunction (POCD) commonly occurs after surgery, particularly in elderly individuals. It is characterized by a notable decline in cognitive performance, encompassing memory, attention, coordination, orientation, verbal fluency, and executive function. This reduction in cognitive abilities contributes to extended hospital stays and heightened mortality. The prevalence of POCD can reach 40% within 1 week following cardiovascular surgery and remains as high as 17% 3 months post-surgery. Furthermore, POCD exacerbates the long-term risk of Alzheimer\'s disease (AD). As a result, numerous studies have been conducted to investigate the molecular mechanisms underlying POCD and potential preventive strategies. This article provides a review of the research progress on POCD.

UNASSIGNED: Post-operative cognitive dysfunction (POCD) is a common central nervous system complication after surgery. Inhaled anesthetic sevoflurane is thought to have harmful effects on the developing and aged nerves, but its effects on adults\' nervous system are less studied and the mechanism is not clear.
UNASSIGNED: Male adult rats were divided into control group and sevoflurane group. Rats from sevoflurane group were received 3.2% sevoflurane + carrier gas (1 L/min O2+1 L/min air) for 2 h, while control group received carrier gas for 2 h. Each group was subsequently divided into 3 subgroups according to the Day 1, Day 3, Day 7 after sevoflurane anesthesia. Morris Water Maze, amyloid-beita (Abeta) and apolipoprotein E (ApoE) mRNA in hippocampus were analyzed. Then, adult ApoE-/- rats were also divided into control group and sevoflurane group. Each group was divided into 3 subgroups according to Day 1, Day 3 and Day 7. Abeta mRNA and protein expression in hippocampus were analyzed.
UNASSIGNED: Compared with the control group, hippocampal Abeta mRNA and protein expression in rats from sevoflurane group significantly increased in hippocampus on Day 7, while ApoE mRNA and protein expression increased on Day 1 and Day 3. There was no difference in times of crossing platforms, time during platform, times across platform quadrant and time percent during platform quadrant between each group. Compared with the control group, hippocampal Abeta and ApoE-/- rats in sevoflurane group did not change.
UNASSIGNED: ApoE modulates hippocampal Abeta deposition and stabilizes learning and memory ability in adult rats after sevoflurane exposure, but this effect is not constant.

The present prospective randomized study was designed to investigate whether the development of Post Operative Cognitive Decline (POCD) is related to anesthesia type in older adults. All patients were screened for delirium and mental status, received baseline neuropsychological assessment, and evaluation of activities of daily living (ADLs). Follow-up assessments were performed at 3-6 months and 12-18 months. Patients were randomized to receive either inhalation anesthesia (ISO) with isoflurane or total intravenous anesthesia (TIVA) with propofol for maintenance anesthesia. ISO (n = 99) and TIVA (n = 100) groups were similar in demographics, preoperative cognition, and incidence of post-operative delirium. Groups did not differ in terms of mean change in memory or executive function from baseline to follow-up. Pre-surgical cognitive function is the only variable predictive of the development of POCD. Anesthetic type was not predictive of POCD. However, ADLs were predictive of post-operative delirium development. Overall, this pilot study represents a prospective, randomized study demonstrating that when examining ISO versus TIVA for maintenance of general anesthesia, there is no significant difference in cognition between anesthetic types. There is also no difference in the occurrence of postoperative delirium. Postoperative cognitive decline was best predicted by lower baseline cognition and functional status.

We investigated the mechanism, whereby tumor necrosis factor-like ligand 1A (TL1A) mediates the A1 differentiation of astrocytes in postoperative cognitive dysfunction (POCD).
The cognitive and behavioral abilities of mice were assessed by Morris water maze and open field tests, while the levels of key A1 and A2 astrocyte factors were detected by RT-qPCR. Immunohistochemical (IHC) staining was used to examine the expression of GFAP, western blot was used to assay the levels of related proteins, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory cytokines.
The results showed that TL1A could promote the progression of cognitive dysfunction in mice. Astrocytes differentiated into A1 phenotype, while unobvious changes were noted in astrocyte A2 biomarkers. Knockout of NLRP3 or intervention with NLRP3 inhibitor could inhibit the effect of TL1A, improving the cognitive dysfunction and suppressing the A1 differentiation.
Our results demonstrate that TL1A plays an important role in POCD in mice, which promotes the A1 differentiation of astrocytes through NLRP3, thereby exacerbating the progression of cognitive dysfunction.

Postoperative cognitive dysfunction (POCD) is a common complication of cognitive decline after surgery and anesthesia. Sevoflurane, as a commonly used anesthetic, was found to cause POCD. Nudix Hydrolase 21 (NUDT21), a conserved splicing factor, has been reported to exert important functions in multiple diseases\' progression. In this study, the effect of NUDT21 on sevoflurane-induced POCD was elucidated. Results showed that NUDT21 was down-regulated in the hippocampal tissue of sevoflurane-induced rats. Morris water maze test results revealed that overexpression of NUDT21 improved sevoflurane-induced cognitive impairment. In addition, TUNEL assay results indicated that enhanced NUDT21 alleviated sevoflurane-induced apoptosis of hippocampal neurons. Furthermore, overexpression of NUDT21 suppressed the sevoflurane-induced LIMK2 expression. Taken together, NUDT21 alleviates sevoflurane-induced neurological damage in rats by down-regulating LIMK2, providing a novel target for the prevention of sevoflurane-induced POCD.

UNASSIGNED: Anesthetic exposure causes learning and memory impairment, the mechanisms of which remain unknown. It has been reported that tumor necrosis factor-α-inducer protein 8-like 2 (TIPE2) is a newly discovered immune negative regulator that is essential for maintaining immune homeostasis. This study aimed to examine the role of TIPE2 in isoflurane-induced postoperative cognitive decline (POCD).
UNASSIGNED: An AAV empty vector and AAV shTIPE2 vector for the knockdown of TIPE2 were injected into the dorsal hippocampus of mice. Mice were continuously exposed to 1.5% isoflurane followed by abdominal exploration. Behavioral tests including the open field test and fear conditioning test were performed on the third and fourth day post-operation. Apoptosis was detected by terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling staining. The kits were used to detect the activity of antioxidant enzymes. Inflammatory cytokine levels were detected by enzyme-linked immunosorbent assay. Signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB (NF-κB) signaling pathway activities were detected by western blotting.
UNASSIGNED: TIPE2 expression increased after isoflurane anesthesia and surgery. TIPE2 deficiency aggravated cognitive impairment in mice and further caused apoptosis and oxidative stress in hippocampal neurons. TIPE2 deficiency induced microglial activation and increased secretion of proinflammatory cytokines. In addition, TIPE2 deficiency promoted STAT3 and NF-κB signaling activation induced by isoflurane anesthesia and after surgery.
UNASSIGNED: TIPE2 may play a neuroprotective role in POCD by regulating STAT3 and NF-κB pathways.

OBJECTIVE: To investigate the effect of energy intake restriction on postoperative cognitive dysfunction (POCD) after internal fixation of tibial fractures in mice.
METHODS: Thirty mice were divided into model groups of internal fixation of tibial fractures with 0%, 20%, 30% and 40% energy intake restriction and sham operation group (n = 6). Novel object recognition task and elevated plus maze test were used to assess the ability of recognition memory and anxiety-related behavior before and one week after surgery. The blood samples were collected from mice on days 1, 3 and 7 after surgery, and the mice were euthanized on the 8th day after surgery. RT-PCR and Western blot were employed to detect the expression of AMPK-SIRT1 pathway-related genes and proteins in the hippocampus. ELISA was used to detect the levels of inflammatory factors in the peripheral blood of mice. Hematoxylin-eosin (H&E) staining and immunofluorescence (IF) staining were used to detect the proliferation, differentiation and injury of hippocampal cells.
RESULTS: The results showed that 20% and 30% energy intake restriction significantly improved the POCD after internal fixation of tibial fractures in mice. Significantly, 30% energy intake restriction reduced the expression of AP-1, NF-κB, CD45, IBA-1, and inflammatory factors IL-1β, IL-6, IL-8 and TNF-α, and increased the expression of AMPK and SIRT1 after the operation. H&E and IF staining showed that 30% energy intake restriction reduced postoperative hippocampal neuronal damage.
CONCLUSIONS: Energy intake restriction can significantly improve POCD after internal fixation of tibial fractures in mice and may provide a new treatment paradigm for POCD patients.