Anesthetic neurotoxicity

PURPOSE: Neurotoxicity concerns have been raised over general anesthesia and sedation medication use in children. Such concerns are largely based on animal studies, historical anesthetic agents, and assessment tools, thus warranting further investigations. Blood biomarkers in detecting neuronal inflammation and apoptosis are novel methods for detecting neuronal damage. Therefore, the aim of this feasibility study was to assess the usefulness of the levels of four plasma biomarkers in dental general anesthesia (DGA) as surrogate markers of neurotoxicity in children...

The potential neurotoxic effects of propofol, an extensively utilized anesthetic, underline the urgency to comprehend its influence on neuronal health. Insights into the role of the RARα-Snhg1-Bdnf network can offer significant advancements in minimizing these effects. The study targets the exploration of the RARα and Snhg1 regulatory network's influence on Bdnf expression in the realm of propofol-induced neurotoxicity. Harnessing the GEO database and utilizing JASPAR and RPISeq for projections, the study embarks on an in-depth analysis employing both in vitro and in vivo models...

Bupivacaine (BUP) is an anesthetic commonly used in clinical practice that when used for spinal anesthesia, might exert neurotoxic effects. Thioredoxin-interacting protein (TXNIP) is a member of the α-arrestin protein superfamily that binds covalently to thioredoxin (TRX) to inhibit its function, leading to increased oxidative stress and activation of apoptosis. The role of TXNIP in BUP-induced oxidative stress and apoptosis remains to be elucidated. In this context, the present study aimed to explore the effects of TXNIP knockdown on BUP-induced oxidative stress and apoptosis in the spinal cord of rats and in PC12 cells through the transfection of adeno-associated virus-TXNIP short hairpin RNA (AAV-TXNIP shRNA) and siRNA-TXNIP, respectively...

Etomidate (ETO) is used as an anesthetic in surgery, but it is being abused in some populations. The damage caused by long-term intake of ETO to intestinal and brain functions is not yet clear, and it remains to be determined whether the drug affects the central nervous system through the gut-brain axis. This study aimed to investigate the neurotoxic and gastrointestinal effects of ETO at doses of 1mg/kg and 3mg/kg in mice over 14 consecutive days. The results showed that long-term injection of ETO led to drug resistance in mice, affecting their innate preference for darkness and possibly inducing dependence on ETO...

BACKGROUND: There are only six past reports of super-refractory status epilepticus induced by spinal anesthesia. None of those patients have died. Only < 15 mg of bupivacaine was administered to all six of them and to our case. Pathophysiology ensuing such cases remains unclear. CASE PRESENTATION: A 27 year old gravida 2, para 1, mother at 37 weeks of gestation came to the operating theater for an elective cesarean section. She had no significant medical history other than controlled hypothyroidism and one episode of food allergy...

Although anesthesia makes painful or uncomfortable diagnostic and interventional health care procedures tolerable, it may also disrupt key cellular processes in neurons and glia, harm the developing brain, and thereby impair cognition and behavior in children. Many years of studies using in vitro, animal behavioral, retrospective database studies in humans, and several prospective clinical trials in humans have been invaluable in discerning the potential toxicity of anesthetics. The objective of this scoping review was to synthetize the evidence from preclinical studies for various mechanisms of toxicity across diverse experimental designs and relate their findings to those of recent clinical trials in real-world settings...

OBJECTIVE: Anesthetics have been linked to cognitive alterations, particularly in the elderly. The current research delineates how Fibroblast Growth Factor 2 (Fgf2) modulates tau protein phosphorylation, contributing to cognitive impairments in aged rats upon sevoflurane administration. METHODS: Rats aged 3, 12, and 18 months were subjected to a 2.5% sevoflurane exposure to form a neurotoxicity model. Cognitive performance was gauged, and the GEO database was employed to identify differentially expressed genes (DEGs) in the 18-month-old cohort post sevoflurane exposure...

BACKGROUND: Bupivacaine (BUP), a long-acting local anesthetic, has been widely used in analgesia and anesthesia. However, evidence strongly suggests that excessive application of BUP may lead to neurotoxicity in neurons. Sphingosine kinase 2 (SPHK2) has been reported to exert neuroprotective effects. In this study, we intended to investigate the potential role and mechanism of SPHK2 in BUP-induced neurotoxicity in dorsal root ganglion (DRG) neurons. METHODS: DRG neurons were cultured with BUP to simulate BUP-induced neurotoxicity  in vitro ...

Surgery and anesthesia are vital medical interventions, but concerns over their potential cognitive side effects, particularly with the use of inhalational anesthetics like sevoflurane, have surfaced. This study delves into the neuroprotective potential of Echinatin against sevoflurane-induced neurotoxicity and the underlying mechanisms. Echinatin, a natural compound, has exhibited anti-inflammatory, antioxidant, and anticancer properties. Sevoflurane, while a popular anesthetic, is associated with perioperative neurocognitive disorders (PND) and neurotoxicity...

Propofol is a frequently used anesthetic. It can induce neurodegeneration and inhibit neurogenesis in the hippocampus. This effect may be temporary. It can, however, become permanent in vulnerable populations, such as the elderly, who are more susceptible to Alzheimer's disease, and neonates and children, whose brains are still developing and require neurogenesis. Current clinical practice strategies have failed to provide an effective solution to this problem. In addition, the molecular mechanism of this toxicity is not fully understood...

The development of local anesthetics revolutionized the performance of painful interventions. Local anesthetics have an effect on voltage-gated sodium channels in nerve fibers and modulate the conduction of impulses. With respect to the chemical structure, local anesthetics can be divided into amide and ester types. The structural differences of local anesthetics have an influence on the duration of action, the degradation pathways and specific side effects. Severe adverse events include cardiotoxicity and neurotoxicity...

BACKGROUND: Chlorpyrifos (CPF) is an organophosphate pesticide that inhibits acetylcholinesterase (AChE) activity. Investigations have also focused on its neurotoxicity, which is independent of AChE inhibition. Here, we evaluated the effect of CPF on oxidative indices in the brain tissue and explored the protective effect of curcumin (Cur) against its toxicity. METHODS: Forty male Wistar rats were divided into five groups, each consisting of eight rats (n = 8) per group...

In recent years, sevoflurane and isoflurane are the most popular anesthetics in general anesthesia for their safe, rapid onset, and well tolerant. Nevertheless, many studies reported their neurotoxicity among pediatric and aged populations. This effect is usually manifested as cognitive impairment such as perioperative neurocognitive disorders. The wide application of sevoflurane and isoflurane during general anesthesia makes their safety a major health concern. Evidence indicates that iron dyshomeostasis and ferroptosis may establish a role in neurotoxicity of sevoflurane and isoflurane...

Sevoflurane, the predominant pediatric anesthetic, has been linked to neurotoxicity in young mice, although the underlying mechanisms remain unclear. This study focuses on investigating the impact of neonatal sevoflurane exposure on cell-type-specific alterations in the prefrontal cortex (PFC) of young mice. Neonatal mice were subjected to either control treatment (60% oxygen balanced with nitrogen) or sevoflurane anesthesia (3% sevoflurane in 60% oxygen balanced with nitrogen) for 2 hours on postnatal days (PNDs) 6, 8, and 10...

Bupivacaine, a common amide local anesthetic, can provide effective analgesia or pain relief but can also cause neurotoxicity, which remains a mounting concern in clinic and animal care. However, the precise underlying mechanisms have not been fully elucidated. A natural compound, notoginsenoside R1 (NG-R1) has been reported to exhibit a neuroprotective role in stress conditions. In this study, we explored the function and mechanism of NG-R1 in alleviating bupivacaine-induced neurotoxicity in mouse hippocampal neuronal (HT-22) and mouse neuroblastoma (Neuro-2a) cell lines...

We have recently shown that the volatile anesthetics isoflurane and sevoflurane acutely enhance the brain uptake of the hydrophilic markers sucrose and mannitol about two-fold from an awake condition, while the combined injection of the anesthetic agents ketamine and xylazine has no effect. The present study investigated two small-molecule hydrophilic drugs with potential neurotoxicity, the antibiotic agents ceftazidime and gentamicin. Transport studies using an in vitro blood-brain barrier (BBB) model, a monolayer of induced pluripotent stem cell-derived human brain microvascular endothelial cells seeded on Transwells, and LC-MS/MS analysis demonstrated the low permeability of both drugs in the range of sucrose, with permeability coefficients of 6...

Perioperative neurocognitive impairment (PND) is a common medical complication in the postoperative period. General anesthesia through volatile anesthetics poses a high risk of POCD. Moreover, the developing brain is especially vulnerable to anesthesia-induced neurotoxicity. Therefore, finding a practical approach to prevent or alleviate neonatal isoflurane (ISO) exposure-induced brain injury and cognitive decline is essential for reducing medical complications following major surgery during the early postnatal period...

INTRODUCTION: Local anesthetic-induced neurotoxicity contributes to perioperative nerve damage; however, the underlying mechanisms remain unclear. Here, we investigated the role of the paraventricular thalamus (PVT)-nucleus accumbens (NAc) projections in neurotoxicity induced by ropivacaine, a local anesthetic agent. METHODS: Ropivacaine (58 mg/kg, intraperitoneal administration) was used to construct the local anesthetic systemic toxicity (LAST) mice model...

Sevoflurane can produce toxicity to the hippocampal tissues of brain, leading to nerve damage, causing learning and cognitive dysfunction. CircRNAs have been indicated to act as a key mediator in anesthetic neurotoxicity. This study focused on the effect of circ_0016760 on sevoflurane‑induced neurological impairment. The GEO database (GSE147277) and RT‑qPCR were used to predict and  measure the circ_0016760 expression. The interaction of circ_0016760 and miR‑145 was verified by dual‑luciferase reporter assay...

Sevoflurane is one of the most widely used inhaled anesthetics. MicroRNAs (miRNAs) have been demonstrated to affect sevoflurane anesthesia-induced neuron damage. The purpose of this study was to investigate the role and mechanism of miR-181a-5p in sevoflurane-induced hippocampal neuronal injury. Primary hippocampal neurons were identified using microscopy and immunofluorescence. The viability and apoptosis of sevoflurane anesthesia-induced neurons were detected by cell counting kit-8 (CCK-8) assay and terminal-deoxynucleoitidyl transferase-mediated nick end-labeling (TUNEL) staining assay, respectively...