Monocyte-Derived Macrophages Aggravate Cardiac Dysfunction After Ischemic Stroke in Mice.

BACKGROUND: Cardiac damage induced by ischemic stroke, such as arrhythmia, cardiac dysfunction, and even cardiac arrest, is referred to as cerebral-cardiac syndrome (CCS). Cardiac macrophages are reported to be closely associated with stroke-induced cardiac damage. However, the role of macrophage subsets in CCS is still unclear due to their heterogeneity. Sympathetic nerves play a significant role in regulating macrophages in cardiovascular disease. However, the role of macrophage subsets and sympathetic nerves in CCS is still unclear. METHODS AND RESULTS: In this study, a middle cerebral artery occlusion mouse model was used to simulate ischemic stroke. ECG and echocardiography were used to assess cardiac function. We used Cx3cr1GFPCcr2RFP mice and NLRP3-deficient mice in combination with Smart-seq2 RNA sequencing to confirm the role of macrophage subsets in CCS. We demonstrated that ischemic stroke-induced cardiac damage is characterized by severe cardiac dysfunction and robust infiltration of monocyte-derived macrophages into the heart. Subsequently, we identified that cardiac monocyte-derived macrophages displayed a proinflammatory profile. We also observed that cardiac dysfunction was rescued in ischemic stroke mice by blocking macrophage infiltration using a CCR2 antagonist and NLRP3-deficient mice. In addition, a cardiac sympathetic nerve retrograde tracer and a sympathectomy method were used to explore the relationship between sympathetic nerves and cardiac macrophages. We found that cardiac sympathetic nerves are significantly activated after ischemic stroke, which contributes to the infiltration of monocyte-derived macrophages and subsequent cardiac dysfunction. CONCLUSIONS: Our findings suggest a potential pathogenesis of CCS involving the cardiac sympathetic nerve-monocyte-derived macrophage axis.

Boron Cluster Renders Organic Radicals Water-Stable for Photothermal Anti-Infections.

Water-stable organic radicals are promising photothermal conversion candidates for photothermal therapy (PTT). However, organic radicals are usually unstable in biological environments, which greatly hinders their wide application. Here, we have developed a chaotropic effect-based and photoinduced water-stable supramolecular radical (MB12-2) for efficient antibacterial PTT. The supramolecular radical precursor MB12-1 was constructed by the chaotropic effect between closo-dodecaborate cluster (B12H122-) and N,N'-dimethylated dipyridinium thiazolo [5,4-d] thiazole (MPT2+). Subsequently, with triethanolamine (TEOA) serving as an electron donor, MB12-1 could transform to its radical form MB12-2 through photoinduced electron transfer (PET) under 435-nm laser irradiation. The N2 adsorption-desorption analysis confirmed that MB12-2 was tightly packed through the introduction of B12H122-, which effectively enhanced its stability via a spatial site-blocked effect. Moreover, the half-life of MB12-2 in water was calculated through ultraviolet-visible light (UV-vis) absorption spectra results for periods as long as 20 days. In addition, in the skin infection model, MB12-2, as a wound dressing, showed remarkable photothermal antibacterial activity (>97%) under 660-nm laser irradiation and promoted wound healing. This study presents a simple method for designing long-term water-stable supramolecular radicals, offering a novel avenue for noncontact treatments for bacterial infections.

Decreased connexin 40 expression of the sinoatrial node mediates ischemic stroke-induced arrhythmia in mice.

BACKGROUND: Arrhythmia is the most common cardiac complication after ischemic stroke. Connexin 40 is the staple component of gap junctions, which influences the propagation of cardiac electrical signals in the sinoatrial node. However, the role of connexin 40 in post-stroke arrhythmia remains unclear. METHODS: In this study, a permanent middle cerebral artery occlusion model was used to simulate the occurrence of an ischemic stroke. Subsequently, an electrocardiogram was utilized to record and assess variations in electrocardiogram measures. In addition, optical tissue clearing and whole-mount immunofluorescence staining were used to confirm the anatomical localization of the sinoatrial node, and the sinoatrial node tissue was collected for RNA sequencing to screen for potential pathological mechanisms. Lastly, the rAAV9-Gja5 virus was injected with ultrasound guidance into the heart to increase Cx40 expression in the sinoatrial node. RESULTS: We demonstrated that the mice suffering from a permanent middle cerebral artery occlusion displayed significant arrhythmia, including atrial fibrillation, premature ventricular contractions, atrioventricular block, and abnormal electrocardiogram parameters. Of note, we observed a decrease in connexin 40 expression within the sinoatrial node after the ischemic stroke via RNA sequencing and western blot. Furthermore, rAAV9-Gja5 treatment ameliorated the occurrence of arrhythmia following stroke. CONCLUSIONS: In conclusion, decreased connexin 40 expression in the sinoatrial node contributed to the ischemic stroke-induced cardiac arrhythmia. Therefore, enhancing connexin 40 expression holds promise as a potential therapeutic approach for ischemic stroke-induced arrhythmia.

Chaotropic Effect-Induced Sol-Gel Transition and Radical Stabilization for Bacterially Sensitive Near-Infrared Photothermal Therapy.

Deep-seated bacterial infections (DBIs) are stubborn and deeply penetrate tissues. Eliminating deep-seated bacteria and promoting tissue regeneration remain great challenges. Here, a novel radical-containing hydrogel (SFT-B Gel) cross-linked by a chaotropic effect was designed for the sensing of DBIs and near-infrared photothermal therapy (NIR-II PTT). A silk fibroin solution stained with 4,4',4″-(1,3,5-triazine-2,4,6-triyl)tris(1-methylpyridin-1-ium) (TPT3+) was employed as the backbone, which could be cross-linked by a closo-dodecaborate cluster (B12H122-) through a chaotropic effect to form the SFT-B Gel. More interestingly, the SFT-B Gel exhibited the ability to sense DBIs, which could generate a TPT2+• radical with obvious color changes in the presence of bacteria. The radical-containing SFT-B Gel (SFT-B★ Gel) possessed strong NIR-II absorption and a remarkable photothermal effect, thus demonstrating excellent NIR-II PTT antibacterial activity for the treatment of DBIs. This work provides a new approach for the construction of intelligent hydrogels with unique properties using a chaotropic effect.

Inhibition of PARP1 improves cardiac function after myocardial infarction via up-regulated NLRC5.

The incidence and mortality rate of myocardial infarction are increasing per year in China. The polarization of macrophages towards the classically activated macrophages (M1) phenotype is of utmost importance in the progression of inflammatory stress subsequent to myocardial infarction. Poly (ADP-ribose) polymerase 1(PARP1) is the ubiquitous and best characterized member of the PARP family, which has been reported to support macrophage polarization towards the pro-inflammatory phenotype. Yet, the role of PARP1 in myocardial ischemic injury remains to be elucidated. Here, we demonstrated that a myocardial infarction mouse model induced cardiac damage characterized by cardiac dysfunction and increased PARP1 expression in cardiac macrophages. Inhibition of PARP1 by the PJ34 inhibitors could effectively alleviate M1 macrophage polarization, reduce infarction size, decrease inflammation and rescue the cardiac function post-MI in mice. Mechanistically, the suppression of PARP1 increase NLRC5 gene expression, and thus inhibits the NF-κB pathway, thereby decreasing the production of inflammatory cytokines such as IL-1ß and TNF-α. Inhibition of NLRC5 promote infection by effectively abolishing the influence of this mechanism discussed above. Interestingly, inhibition of NLRC5 promotes cardiac macrophage polarization toward an M1 phenotype but without having major effects on M2 macrophages. Our results demonstrate that inhibition of PARP1 increased NLRC5 gene expression, thereby suppressing M1 polarization, improving cardiac function, decreasing infarct area and attenuating inflammatory injury. The aforementioned findings provide new insights into the proinflammatory mechanisms that drive macrophage polarization following myocardial infarction, thereby introducing novel potential targets for future therapeutic interventions in individuals affected by myocardial infarction.

Chaotropic Effect-Induced Self-Assembly of the Malachite Green and Boron Cluster for Toxicity Regulation and Photothermal Therapy.

Malachite green (MG), a toxic antibacterial agent, is widely used in the farming industry. Effectively regulating the biotoxicity of this highly water-soluble cationic dye is challenging. Here, we present a novel strategy to reduce the biotoxicity of MG through the self-assembly of MG and the closo-dodecaborate cluster ([B12H12]2-) driven by the chaotropic effect. [B12H12]2- and MG in an aqueous solution can rapidly form an insoluble cubic-type supramolecular complex (B12-MG), and the original toxicity of MG is completely suppressed. Surprisingly, this supramolecular complex, B12-MG, has a strong UV-vis absorption peak at 600-800 nm and significant photothermal conversion efficiency under 660 nm laser irradiation. On this basis, B12-MG, the supramolecular complex, can be used as an efficient photothermal agent for antimicrobial photothermal therapy (PTT) both in vitro and in vivo. As a molecular chaperone of MG, [B12H12]2- not only can be applied as an antidote to regulate the biotoxicity of MG but also provides a novel method for the construction of photothermal agents for PTT based on the chaotropic effect.

Intrathecal rapamycin attenuates the mechanical hyperalgesia of paclitaxel-induced peripheral neuropathy in mice.

Paclitaxel is an extensively used chemotherapy antitumor drug and paclitaxel-induced peripheral neuropathy (PIPN) is one of the most common side effect. Rapamycin, originally used as an adjuvant drug for chemotherapy, has recently been found to possess potential neuroprotective activities. Our purposes of this study are to verify the effect of rapamycin on PIPN, which contributes to a new target for PIPN treatment. Mice were given paclitaxel or rapamycin with different injection methods. Paw withdrawal threshold was tested at different time points for mechanical sensitivity assessment. Administration of paclitaxel, both 2 mg/kg and 5 mg/kg, could induce mechanical hypersensitivity. 0.01 mg intrathecal injection of rapamycin showed the best effect on attenuate the mechanical hyperalgesia of PIPN. Intrathecal injection of only rapamycin would not induce the mechanical hyperalgesia while when rapamycin and paclitaxel were used together the mechanical hyperalgesia induced by paclitaxel could be attenuated. Paclitaxel could induce mechanical hyperalgesia in mice and rapamycin could attenuate such mechanical hyperalgesia of PIPN.

Fentanyl inhibits cell invasion and migration by modulating NF-κB activation in glioma.

Fentanyl is widely used for anesthesia and analgesia in cancer patients. Recent studies have revealed its anti-growth effect in several categories of cancer. Gliomas are the most common primary tumors in the central nervous system with poor prognosis. To investigate the effects of fentanyl on gliomas, glioma cells were treated with different concentrations of fentanyl both in vitro and in vivo. Consequences of proliferation and invasive phenotypes, and related protein expression were evaluated in two human glioma cell lines (U251 and U87). Naloxone, Mu Opioid Receptor (MOR) antagonist, was introduced into culture media to assess the involvement of MOR in Fentanyl-mediated changes. When compared with control group, it could be found that Fentanyl inhibited function of glioma cells only at high concentrations. Western blot and immunofluorescence results revealed that Fentanyl exerted its action via modulating NF-κB (P65) activation which is likely independent of MOR. Moreover, overexpression of P65 by transfection P65-expressing vector restored the invasion and migration of glioma cells, which were inhibited by Fentanyl. In summary, this study showed that opioid pain medication Fentanyl was capable of decreasing invasiveness of glioma cells at a high concentration both in vitro and in vivo, likely via modulating P65 activation.

Supramolecularly assisted chlorhexidine-bacterial membrane interaction with enhanced antibacterial activity and reduced side effects.

Bacterial infection has emerged as a grievous threat to public health, and lots of antibacterial agents were developed to solve this issue. However, enhancing the antibacterial activity of antibacterial agents while reducing their side effects remains a challenge. Herein, a supramolecular antibacterial agent based on the host-guest interaction between cucurbit[7]uril (CB[7]) and chlorhexidine (CHX) was designed. CHX can be encapsulated in the cavity of CB[7] to form a 1:3 host-guest complex (CHX-3CB[7]). It was amazingly found that this supramolecular complex could display higher antibacterial activity than CHX alone. Electrospray mass spectrometry and UV-vis spectra revealed that the introduction of CB[7] promoted the protonation of N-atoms on CHX, resulting in stronger ion interaction with phospholipids and thus enhancing the destruction of the bacterial membrane. Scanning electron microscopy (SEM), surface ζ-potentials and outer/inner membrane integrity assays also reveal that the introduction of CB[7] aggravates the rupture of membrane. What is more, the cytotoxicity and irritation of CHX were decreased by forming the host-guest complex with CB[7]. This work provides a paradigm for enhancing antibacterial activity and reducing side effects of drugs through supramolecular chemistry.

Isoflurane Attenuates Cerebral Ischaemia-Reperfusion Injury via the TLR4-NLRP3 Signalling Pathway in Diabetic Mice.

Ischaemic stroke is a severe disease worldwide. Restoration of blood flow after ischaemic stroke leads to cerebral ischaemia-reperfusion injury (CIRI). Various operations, such as cardiac surgery with deep hypothermic circulatory arrest, predictably cause cerebral ischaemia. Diabetes is related to the occurrence of perioperative stroke and exacerbates neurological impairment after stroke. Therefore, the choice of anaesthetic drugs has certain clinical significance for patients with diabetes. Isoflurane (ISO) exerts neuroprotective and anti-neuroinflammatory effects in patients without diabetes. However, the role of ISO in cerebral ischaemia in the context of diabetes is still unknown. Toll-like receptor 4 (TLR4) and NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome activation play important roles in microglia-mediated neuroinflammatory injury. In this study, we treated a diabetic middle cerebral artery occlusion mouse model with ISO. We found that diabetes exacerbated cerebral ischaemia damage and that ISO exerted neuroprotective effects in diabetic mice. Then, we found that ISO decreased TLR4-NLRP3 inflammasome activation in microglia and the excessive autophagy induced by CIRI in diabetic mice. The TLR4-specific agonist CRX-527 reversed the neuroprotective effects of ISO. In summary, our study indicated that ISO exerts neuroprotective effects against the neuroinflammation and autophagy observed during diabetic stroke via the TLR4-NLRP3 signalling pathway.

Cerebral-Cardiac Syndrome and Diabetes: Cardiac Damage After Ischemic Stroke in Diabetic State.

Cerebral-cardiac syndrome (CCS) refers to cardiac dysfunction following varying brain injuries. Ischemic stroke is strongly evidenced to induce CCS characterizing as arrhythmia, myocardial damage, and heart failure. CCS is attributed to be the second leading cause of death in the post-stroke stage; however, the responsible mechanisms are obscure. Studies indicated the possible mechanisms including insular cortex injury, autonomic imbalance, catecholamine surge, immune response, and systemic inflammation. Of note, the characteristics of the stroke population reveal a common comorbidity with diabetes. The close and causative correlation of diabetes and stroke directs the involvement of diabetes in CCS. Nevertheless, the role of diabetes and its corresponding molecular mechanisms in CCS have not been clarified. Here we conclude the features of CCS and the potential role of diabetes in CCS. Diabetes drives establish a "primed" inflammatory microenvironment and further induces severe systemic inflammation after stroke. The boosted inflammation is suspected to provoke cardiac pathological changes and hence exacerbate CCS. Importantly, as the key element of inflammation, NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome is indicated to play an important role in diabetes, stroke, and the sequential CCS. Overall, we characterize the corresponding role of diabetes in CCS and speculate a link of NLRP3 inflammasome between them.

Malaria: elimination tale from Yunnan Province of China and new challenges for reintroduction.

BACKGROUND: Eradication of infectious disease is the sanctified public health and sustainable development goal around the world. MAIN BODY: Three antimalarial barriers were developed to control imported malarial cases, and an effective surveillance strategy known as the "1-3-7 approach" was developed to eliminate malaria from the Chinese population. From 2011 to 2019, 5254 confirmed malaria cases were reported and treated in Yunnan Province, China. Among them, 4566 cases were imported from other countries, and 688 cases were indigenous from 2011 to 2016. Since 2017, no new local malarial case has been reported in China. Thus, malaria has been completely eliminated in Yunnan Province. However, malaria is detected in overseas travellers on a regular basis, such as visitors from neighbouring Myanmar. CONCLUSION: Hence, the strategies should be further strengthened to maintain a robust public health infrastructure for disease surveillance and vector control programs in border areas. Such programs should be supported technically and financially by the government to avert the possibility of a malarial resurgence in Yunnan Province.

Exaggerated activities of TRPM7 underlie bupivacaine-induced neurotoxicity in the SH-SY5Y cells preconditioned with high glucose.

Hyperglycemia is considered a risk factor for the enhancement of local anesthetic-induced neurotoxicity. Transient receptor potential melastatin 7 (TRPM7), a kinase-coupled cation channel, has been implicated in a variety of neuropathological processes, including intracellular calcium disturbance and high glucose-induced neuropathy. In this study, we investigated whether TRPM7-related pathophysiology is involved in bupivacaine-induced neurotoxicity in SH-SY5Y cells and how hyperglycemia acts as a risk factor. For initial neurotoxicity evaluation, it was confirmed that cell damage and apoptosis induced by acute exposure to bupivacaine were dependent on its concentration and glucose preconditioning. High glucose preconditioning facilitated the bupivacaine-induced fast and temporary rise in intracellular free calcium concentration ([Ca2+ ]i ), which was attributed to both calcium influx through TRPM7 and calcium store release. Additionally, bupivacaine was shown to increase TRPM7-like currents, particularly in cells preconditioned with high glucose. Bupivacaine-induced neurotoxicity in hyperglycemia was correlated with extracellular signal-regulated kinase (ERK), but not protein kinase B (AKT) activation. Inhibition of TRPM7 and ERK activity alleviates bupivacaine neurotoxicity. These results suggest that therapeutically targeting TRPM7-related pathophysiological changes could be a potential strategy for treating local anesthetic-induced neurotoxicity exacerbated by hyperglycemia.

Macrophage-NLRP3 Inflammasome Activation Exacerbates Cardiac Dysfunction after Ischemic Stroke in a Mouse Model of Diabetes.

Ischemic stroke is one of the leading causes of death worldwide. In the post-stroke stage, cardiac dysfunction is common and is known as the brain-heart interaction. Diabetes mellitus worsens the post-stroke outcome. Stroke-induced systemic inflammation is the major causative factor for the sequential complications, but the mechanism underlying the brain-heart interaction in diabetes has not been clarified. The NLRP3 (NLR pyrin domain-containing 3) inflammasome, an important component of the inflammation after stroke, is mainly activated in M1-polarized macrophages. In this study, we found that the cardiac dysfunction induced by ischemic stroke is more severe in a mouse model of type 2 diabetes. Meanwhile, M1-polarized macrophage infiltration and NLRP3 inflammasome activation increased in the cardiac ventricle after diabetic stroke. Importantly, the NLRP3 inflammasome inhibitor CY-09 restored cardiac function, indicating that the M1-polarized macrophage-NLRP3 inflammasome activation is a pathway underlying the brain-heart interaction after diabetic stroke.

Response of Chinese Anesthesiologists to the COVID-19 Outbreak.

The coronavirus disease 2019, named COVID-19 officially by the World Health Organization (Geneva, Switzerland) on February 12, 2020, has spread at unprecedented speed. After the first outbreak in Wuhan, China, Chinese anesthesiologists encountered increasing numbers of infected patients since December 2019. Because the main route of transmission is via respiratory droplets and close contact, anesthesia providers are at a high risk when responding to the devastating mass emergency. So far, actions have been taken including but not limited to nationwide actions and online education regarding special procedures of airway management, oxygen therapy, ventilation support, hemodynamic management, sedation, and analgesia. As the epidemic situation has lasted for months (thus far), special platforms have also been set up to provide free mental health care to all anesthesia providers participating in acute and critical caring for COVID-19 patients. The current article documents the actions taken, lesson learned, and future work needed.

High Glucose Enhances Bupivacaine-Induced Neurotoxicity via MCU-Mediated Oxidative Stress in SH-SY5Y Cells.

Bupivacaine, a typical local anesthetic, induces neurotoxicity via reactive oxygen species regulation of apoptosis. High glucose could enhance bupivacaine-induced neurotoxicity through regulating oxidative stress, but the mechanism of it is not clear. Mitochondrial calcium uniporter (MCU), a key channel for regulating the mitochondrial Ca2+ (mCa2+) influx, is closely related to oxidative stress via disruption of mCa2+ homeostasis. Whether MCU is involved in high glucose-sensitized bupivacaine-induced neurotoxicity remains unknown. In this study, human neuroblastoma (SH-SY5Y) cells were cultured with high glucose and/or bupivacaine, and the data showed that high glucose enhanced bupivacaine-induced MCU expression elevation, mCa2+ accumulation, and oxidative damage. Next, Ru360, an inhibitor of MCU, was employed to pretreated SH-SY5Y cells, and the results showed that it could decrease high glucose and bupivacaine-induced mCa2+ accumulation, oxidative stress, and apoptosis. Further, with the knockdown of MCU with a specific small interfering RNA (siRNA) in SH-SY5Y cells, we found that it also could inhibit high glucose and bupivacaine-induced mCa2+ accumulation, oxidative stress, and apoptosis. We propose that downregulation expression or activity inhibition of the MCU channel might be useful for restoring the mitochondrial function and combating high glucose and bupivacaine-induced neurotoxicity. In conclusion, our study demonstrated the crucial role of MCU in high glucose-mediated enhancement of bupivacaine-induced neurotoxicity, suggesting the possible use of this channel as a target for curing bupivacaine-induced neurotoxicity in diabetic patients.

Effects of baicalin on diabetic neuropathic pain involving transient receptor potential vanilloid 1 in the dorsal root ganglia of rats.

Diabetic peripheral neuropathy is the most common complication of diabetes mellitus and leads to sensory symptoms, including diabetic neuropathic pain (DNP). DNP is a major public health problem because it has a considerable impact on life quality of diabetes mellitus patients. Therefore, development of novel effective analgesics for DNP relief and treatment is warranted. Transient receptor potential vanilloid 1 (TRPV1) has a crucial role in nociceptive transmission under pathological forms of pain. Baicalin is a flavonoid compound extracted from a medicinal herb, Huang Qin, it possesses antioxidant properties and has an analgesic effect on nitroglycerin-induced migraine in rats and neuropathic pain in spinal nerve ligation rats. However, the effects of baicalin on DNP are unclear. Therefore, the aim of this study is to examine the effects of baicalin on DNP. Our data show that a single dose of baicalin (40 µg/kg) had a transient analgesic effect on streptozotocin (STZ)-induced DNP rats. Moreover, cumulative injection of baicalin prevented the development of STZ-induced DNP in rats in a dose-dependent manner. In addition, baicalin dose-dependently suppressed the expression of TRPV1 in dorsal root ganglia of STZ-induced DNP rats. Therefore, the analgesic role of baicalin in DNP probably occurred through TRPV1. Baicalin may play an important analgesic role in DNP and might serve as a potential compound in clinical treatment and prevention of DNP.

Inhibition of NLRP3 Inflammasome Ameliorates Cerebral Ischemia-Reperfusion Injury in Diabetic Mice.

Sustained activation of NLRP3 inflammasome is closely related to diabetes and stroke. However, it is unknown whether NLRP3 inflammasome plays an essential role in stroke in diabetes. We aim to investigate the effect and the potential mechanism of NLRP3 inflammasome in diabetic mice with cerebral ischemia-reperfusion injury. A type 2 diabetic mouse model was induced by a high-fat diet and streptozotocin (STZ). Diabetic mice received MCC950 (the specific molecule NLRP3 inhibitor) or vehicle 60 minutes before the middle cerebral artery occlusion (MCAO) and reperfusion. MCC950 reduced the neurological deficit score of 24 h after cerebral ischemia reperfusion and improved the 28-day survival rate of cerebral ischemia-reperfusion injury in diabetic mice. Furthermore, we found that the mRNA transcription levels of NLRP3, IL-1ß, and caspase-1 in the core ischemic area were remarkably amplified in diabetic mice with cerebral ischemia-reperfusion injury, whereas this phenomenon was obviously attenuated by MCC950 pretreatment. In conclusion, the NLRP3 inflammasome was involved in the complex diseases of diabetic stroke. MCC950, the NLRP3 specific inhibitor, ameliorated diabetic mice with cerebral ischemia-reperfusion injury and improved the 28-day survival rate during the recovery stage of ischemic stroke.

Waste anesthetic gas exposure and strategies for solution.

As inhaled anesthetics are widely used, medical staff have inevitably suffered from exposure to anesthetic waste gases (WAGs). Whether chronic exposure to WAGs has an impact on the health of medical staff has long been a common concern, but conclusions are not consistent. Many measures and equipment have been proposed to reduce the concentration of WAGs as far as possible. This review aims to dissect the current exposure to WAGs and its influence on medical staff in the workplace and the environment, and summarize strategies to reduce WAGs.

Dexmedetomidine mitigates isoflurane-induced neurodegeneration in fetal rats during the second trimester of pregnancy.

Dexmedetomidine has significant neuroprotective effects. However, whether its protective effects can reduce neurotoxicity caused by isoflurane in fetal brain during the second trimester of pregnancy remains unclear. In this study, timed-pregnancy rats at gestational day 14 spontaneously inhaled 1.5% isoflurane for 4 hours, and were intraperitoneally injected with dexmedetomidine at dosages of 5, 10, 20, and 20 µg/kg 15 minutes before inhalation and after inhalation for 2 hours. Our results demonstrate that 4 hours after inhaling isoflurane, 20 µg/kg dexmedetomidine visibly mitigated isoflurane-induced neuronal apoptosis, reversed downregulation of brain-derived neurotrophic factor expression, and lessened decreased spatial learning and memory ability in adulthood in the fetal rats. Altogether, these findings indicate that dexmedetomidine can reduce neurodegeneration induced by isoflurane in fetal rats during the second trimester of pregnancy. Further, brain-derived neurotrophic factor participates in this process.