Khalid Saad Alharbi, Waleed Hassan Almalki, Sami I Alzarea, Imran Kazmi, Fahad A Al-Abbasi, Obaid Afzal, Abdulmalik Saleh Alfawaz Altamimi, Mohammed Albratty, Asim Najmi, Gaurav Gupta
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引用次数: 0
摘要
全身麻醉剂(GA)已在临床上持续使用了 170 多年,数以百万计的年轻人和老年人接触过全身麻醉剂,以缓解围手术期的不适和进行侵入性检查。临床前研究表明,急性和慢性暴露于 GA 的新生啮齿动物会出现记忆和学习障碍,这可能是由于兴奋性和抑制性神经递质之间的不平衡造成的,而这种不平衡与神经发育障碍有关。然而,麻醉诱导出生后晚期小鼠发生改变背后的机制尚未确定。在这篇叙述性综述中,我们介绍了关于生命早期麻醉暴露介导的基因表达改变的知识现状,重点是对异丙酚、氯胺酮和异氟醚的深入了解,以及网络效应和随后导致长期神经认知异常的生化变化之间的关系。我们的综述为麻醉剂的病理事件和相关转录变化提供了有力的证据和清晰的图景,这将为研究人员阐明核心观点、深入了解分子和遗传机制提供新的见解。这些发现也有助于为了解急性和慢性接触麻醉剂导致的神经病理加剧、认知受损和 LTP 提供更多证据,这将有利于预防和治疗阿尔茨海默病等多种疾病。鉴于医疗实践中有许多程序需要连续或多次接触麻醉剂,我们的综述将为了解这些物质对人脑和认知可能产生的不利影响提供重要启示。
Anaesthesia-induced Changes in Genomic Expression Leading to Neurodegeneration.
General anaesthetics (GA) have been in continuous clinical use for more than 170 years, with millions of young and elderly populations exposed to GA to relieve perioperative discomfort and carry out invasive examinations. Preclinical studies have shown that neonatal rodents with acute and chronic exposure to GA suffer from memory and learning deficits, likely due to an imbalance between excitatory and inhibitory neurotransmitters, which has been linked to neurodevelopmental disorders. However, the mechanisms behind anaesthesia-induced alterations in late postnatal mice have yet to be established. In this narrative review, we present the current state of knowledge on early life anaesthesia exposure-mediated alterations of genetic expression, focusing on insights gathered on propofol, ketamine, and isoflurane, as well as the relationship between network effects and subsequent biochemical changes that lead to long-term neurocognitive abnormalities. Our review provides strong evidence and a clear picture of anaesthetic agents' pathological events and associated transcriptional changes, which will provide new insights for researchers to elucidate the core ideas and gain an in-depth understanding of molecular and genetic mechanisms. These findings are also helpful in generating more evidence for understanding the exacerbated neuropathology, impaired cognition, and LTP due to acute and chronic exposure to anaesthetics, which will be beneficial for the prevention and treatment of many diseases, such as Alzheimer's disease. Given the many procedures in medical practice that require continuous or multiple exposures to anaesthetics, our review will provide great insight into the possible adverse impact of these substances on the human brain and cognition.
期刊介绍:
Aims & Scope
CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes.
CNS & Neurological Disorders - Drug Targets publishes guest edited thematic issues written by leaders in the field covering a range of current topics of CNS & neurological drug targets. The journal also accepts for publication original research articles, letters, reviews and drug clinical trial studies.
As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal is essential reading for all pharmaceutical scientists involved in drug discovery and development.