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Alzheimer's disease (AD) is one of the greatest public health problems in the US, and its impact will only increase with demographic changes anticipated in the coming decades. Post-operative cognitive dysfunction (POCD), a disorder including impairment of learning and memory following anesthesia and surgery, can significantly affect post-operative recovery of patients. The short-term and long-term effects of general anesthesia on aging brain function represent a burgeoning area of research interest.
The long-term mission of our lab (The Geriatric Anesthesia Research Unit) is to improve the perioperative experience of the elderly patient undergoing surgery. Our research focus on determining the neuropathogenesis of AD and POCD, and assessing the potential neurotoxicity of anesthesia. Specifically, we study the effects of anesthetics on apoptosis, cell death, beta-amyloid protein metabolism and neuroinflammation in cultured cells, animals and humans.
Description of Research
Our own laboratory studies have suggested that perioperative factors such as hypoxia, hypocapnia, surgery, anesthetics, sleep deprivation and pain may contribute to neuropathogenesis of Alzheimer's disease (AD), postoperative cognitive dysfunction (POCD), and delirium. Future projects in the Geriatric Anesthesia Research Unit in the Department of Anesthesia, Critical Care and Pain Medicine at MGH will explore the nature of the relationship between these perioperative factors and AD, work that may shed more light on AD neuropathogenesis; we will investigate the perioperative factors associated with POCD and attempt to establish a possible association between these factors and delirium. Our work proceeds at both the cellular and molecular levels in cultured cells, neurons, mice and human subjects, and we employ such techniques as somatic gene transfer, genetic modification of animal models, RNA interference, RT-PCR, and immunocytochemistry; we also use various pharmacological tools and behavioral evaluations (e.g., Morris Water Maze and Fear Conditioning Test) when these are indicated. These efforts may illustrate whether general anesthesia, surgery and other perioperative factors can initiate or accelerate the development of AD, POCD and delirium. The results of these studies will ultimately guide clinicians with regard to how to provide the safest anesthesia care for patients.
A team of researchers from Massachusetts General Hospital and the Rowland Institute at Harvard University have used a specialized nanoprobe developed by the Harvard/Rowland investigators to directly measure levels of key proteins within living, cultured cells.
The pain caused by a surgical incision may contribute to the risk of postoperative cognitive dysfunction, a sometimes transient impairment in learning and memory that affects a small but significant number of patients in the days following a surgical procedure.
Two studies in mice suggest that several factors may combine to induce impairments in learning and memory, accompanied by the inflammation of brain tissue, in young mammals receiving general anesthesia and that the offspring of animals that received general anesthesia during pregnancy may show the same effects.
The association of the inhaled anesthetic isoflurane with Alzheimer's-disease-like changes in mammalian brains may by caused by the drug's effects on mitochondria, the structures in which most cellular energy is produced.
The Department of Anesthesia, Critical Care and Pain Medicine spotlights Zhongcong Xie, MD.
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