Aims: Hypoxic–ischemic brain injury (HIBI) often results in cognitive impairments. Herein, we investigated the roles of ferroptosis in HIBI and the underlying signaling pathways.Methods: Ferrostatin‐1 (Fer‐1) or resveratrol (Res) treatments were administered intracerebroventricularly 30 min before HIBI in 7‐day‐old rats. Glutathione peroxidase 4 (GPx4) expression, malondialdehyde (MDA) concentration, iron content, mitochondrial morphology, and the expression of silent information regulator factor 2‐related enzyme 1 (SIRT1) and nuclear factor erythroid‐2‐related factor 2 (Nrf2) were measured after HIBI. Additionally, the weight ratio of left/right hemisphere, brain morphology, Nissl staining, and the Morris water maze test were conducted to estimate brain damage.Results: At 24‐h post‐HIBI, GPx4 expression was decreased, and MDA concentration and iron content were increased in the hippocampus. HIBI led to mitochondrial atrophy, brain atrophy/damage, and resultant learning and memory impairments, which were alleviated by Fer‐1‐mediated inhibition of ferroptosis. Furthermore, Res‐mediated SIRT1 upregulation increased Nrf2 and GPx4 expression, thereby attenuating ferroptosis, reducing brain atrophy/damage, and improving learning and memory abilities.Conclusion: The results demonstrated that during HIBI, ferroptosis occurs via the SIRT1/Nrf2/GPx4 signaling pathway, suggesting it as a potential therapeutic target for inhibiting ferroptosis and ameliorating HIBI‐induced cognitive impairments.

Background: Postpartum depression (PPD) is a common mental disease happens in perinatal period. Ketamine as an anesthesia and analgesia drug has been used for a long time. In recent years, ketamine is proved to have an antidepression effect with a single administration. We hypothesized that intraoperative ketamine can reduce postpartum depressive symptoms after cesarean delivery.Methods: In a randomized, double‐blind, placebo‐controlled study trail, healthy women scheduled for cesarean delivery were randomly assigned to receive intravenous ketamine (0.25 mg/kg diluted to 5 ml with 0.9% saline) or placebo (5 ml of 0.9% saline) within 5 min following clamping of the neonatal umbilical cord. The primary outcome was the degree of postpartum depressive symptoms, which was evaluated by Edinburgh Postnatal Depression Scale (EPDS, a threshold of 9/10 was used) at 1 week, 2 weeks, and 1 month after delivery. The secondary outcome was the numerical rating scale (NRS) score of pain at 2 days postpartum. This trail is registered in the Chinese Clinical Trial Registry, number ChiCTR1900022464.Results: Between 26 January 2019 and 15 July 2019, 502 subjects were screened and 330 were randomly allocated: 165 (50%) to the ketamine group and 165 (50%) to the placebo group. There were significant differences in the degree of postpartum depressive symptoms between subjects in the ketamine group and the placebo group at 1 week postpartum (13.1% vs. 22.6%, respectively; p = .029). However, no difference was found between subjects in the two groups at 2 weeks (11.8% vs. 16.8%, respectively; p = .209) and 1 month postpartum (10.5% vs. 14.2%, respectively; p = .319). The NRS score of wound pain (3.0 ± 0.9 vs. 4.0 ± 1.0, respectively; p < .001) and uterine contraction pain (3.0 ± 0.9 vs. 4.1 ± 0.9, respectively; p < .001) was lower in the ketamine group at 2 days postpartum compared with placebo group. The prevalence of headache, hallucination, and dizziness was higher in the ketamine group than the placebo group during the operation.Conclusions: Operative intravenous ketamine (0.25 mg/kg) can reduce the postpartum depressive symptoms for 1 week. The long‐time effect is remained to be seen.

Objective: With an aging population and advances in medicine, more research focuses on health and longevity in geriatric adults. Recently, frailty has gradually emerged to assess physical conditions. Frailty can be generally described as a multi-dimensional situation of increased vulnerabilities to both endogenous and exogenous stressors. The objective of the review was to evaluate the predictive value of frailty on adverse outcomes in geriatric hip fracture patients.Materials and Methods: We searched PubMed, Embase, Web of Science, and the Cochrane library for relevant literature about the connection between frailty and poor outcomes in hip fracture elders.Results: Eleven studies involving a total of 45,979 participants were selected in our study. Our results indicated that frailty could significantly predict postoperative and in-patient complications (OR, 1.46; 95% CI, 1.13–1.90; I² = 77.4%). Frail elders had higher risk of inpatient mortality (OR, 1.68; 95% CI, 1.26–2.25; I² = 0.0%), 6-month mortality (OR, 1.46; 95% CI, 1.25–1.72; I² = 0.0%) and ≥1-year mortality (OR, 2.24; 95% CI, 1.66–3.04; I² = 91.3%). Furthermore, the risk of prolonged hospital stays was 1.15 times more likely in frail patients (95% CI, 1.03–1.28; I² = 14.8%).Conclusion: Frailty can predict adverse outcomes effectively in geriatric hip fracture patients.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails.

Sirt1, a member of the sirtuins family, is a nicotinamide adenosine dinucleotide (NAD⁺)-dependent deacetylase. It can be involved in the regulation of several processes including inflammatory response, apoptosis, oxidative stress, energy metabolism, and autophagy by exerting deacetylation. Nuclear factor-κB (NF-κB), a crucial nuclear transcription factor with specific DNA binding sequences, exists in almost all cells and plays a vital role in several biological processes involving inflammatory response, immune response, and apoptosis. As the hub of multiple intracellular signaling pathways, the activity of NF-κB is regulated by multiple factors. Sirt1 can both directly deacetylate NF-κB and indirectly through other molecules to inhibit its activity. We would like to emphasize that Sirt1/NF-κB is a signaling pathway that is closely related to neuroinflammation. Many recent studies have demonstrated the neuroprotective effects of Sirt1/NF-κB signaling pathway activation applied to the treatment of neurological related diseases. In this review, we focus on new advances in the neuroprotective effects of the Sirt1/NF-κB pathway. First, we briefly review Sirt1 and NF-κB, two key molecules of cellular metabolism. Next, we discuss the connection between NF-κB and neuroinflammation. In addition, we explore how Sirt1 regulates NF-κB in nerve cells and relevant evidence. Finally, we analyze the therapeutic effects of the Sirt1/NF-κB pathway in several common neuroinflammation-related diseases.

Numerous animal studies have demonstrated that commonly-used general anesthetics may result in cognitive impairment in the immature brain. The prevailing theory is that general anesthetics could induce developmental neurotoxicity via enhanced apoptosis. In addition, inhibited proliferation induced by anesthetics has also been reported. So far, whether autophagy, a well-conserved cellular process that is critical for cell fate, also participates in anesthesia-induced neurotoxicity remains elusive. Here, we first examined autophagy-related changes after sevoflurane exposure and the effect of autophagy on apoptosis and proliferation, and we also explored the underlying mechanisms of autophagy activation. Pregnant rats were exposed to 2% or 3.5% sevoflurane for 2 hours on gestational day 14 (G14); then, markers of autophagy and expression of autophagy pathway components were measured in fetal brains 2 hours, 12 hours, 24 hours, 48 hours after anesthesia. Changes in neural stem cell (NSC) apoptosis, neurogenesis, neuron quantity and learning and memory function were examined after administration of an autophagy or PTEN inhibitor. The expression of microtubule-associated protein 1 light chain 3 (LC3)-Ⅱ, Beclin-1 and phosphatase and tensin homolog on chromosome 10 (PTEN) were increased in the 3.5% sevoflurane group, while Sequestosome 1 (P62/SQSTM1), phospho-protein kinase B/protein kinase B (p-Akt/Akt) and mammalian target of rapamycin (mTOR) were decreased. 3-methyladenine (3-MA), an inhibitor of autophagy, or dipotassium bisperoxo-(5-hydroxypyridine-2-carboxyl)-oxovanadate (V) (bpV), a PTEN inhibitor, significantly attenuated the activation of autophagy, reversed the decreased expression of B-cell lymphoma-2 (Bcl-2) and reduced the number of terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) positive cells, ameliorated the decline of Nestin expression, Ki67 positive cell rate, neuron quantity and cross platform times, and shortened the prolonged escape latency. Our results demonstrated that 2 hours 3.5% sevoflurane exposure at G14 induced excessive autophagy in the fetal brain via the PTEN/Akt/mTOR pathway. Autophagy inhibition reversed anesthesia-induced neural stem cell apoptosis, proliferation decline and memory deficits.

Background: When neonatal rats suffer hypoxic-ischemic brain injury (HIBI), autophagy is over-activated in the hippocampus, and inhibition of autophagy provides neuroprotection. The aim of this study was to investigate the possible roles of autophagy and Ezh2-regulated Pten/Akt/mTOR pathway in sevoflurane post-conditioning (SPC)-mediated neuroprotection against HIBI in neonatal rats. Methods: Seven-day-old Sprague–Dawley rats underwent left common artery ligation followed by 2 h hypoxia as described in the Rice–Vannucci model. The roles of autophagy and the Ezh2-regulated Pten/Akt/mTOR signaling pathway in the neuroprotection conferred by SPC were examined by left-side intracerebroventricular injection with the autophagy activator rapamycin and the Ezh2 inhibitor GSK126. Results: SPC was neuroprotective against HIBI through the inhibition of over-activated autophagy in the hippocampus as characterized by the rapamycin-induced reversal of neuronal density, neuronal morphology, cerebral morphology, and the expression of the autophagy markers, LC3B-II and Beclin1. SPC significantly increased the expression of Ezh2, H3K27me3, pAkt, and mTOR and decreased the expression of Pten induced by HI. The Ezh2 inhibitor, GSK126, significantly reversed the SPC-induced changes in expression of H3K27me3, Pten, pAkt, mTOR, LC3B-II, and Beclin1. Ezh2 inhibition also reversed SPC-mediated attenuation of neuronal loss and behavioral improvement in the Morris water maze. Conclusion: These results indicate that SPC inhibits excessive autophagy via the regulation of Pten/Akt/mTOR signaling by Ezh2 to confer neuroprotection against HIBI in neonatal rats.