Progress in neuro-psychopharmacology & biological psychiatry
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Dec 2013
ReviewDual effects of neuroprotection and neurotoxicity by general anesthetics: role of intracellular calcium homeostasis.
Although general anesthetics have long been considered neuroprotective, there are growing concerns about neurotoxicity. Preclinical studies clearly demonstrated that commonly used general anesthetics are both neuroprotective and neurotoxic, with unclear mechanisms. ⋯ On the other hand, general anesthetics at high concentrations for prolonged duration are lethal stress factors which induce neuronal damage by over activation of InsP3R and excessive and abnormal Ca(2+) release from ER. This review emphasizes the dual effects of both neuroprotection and neurotoxicity via differential regulation of intracellular Ca(2+) homeostasis by commonly used general anesthetics and recommends strategy to maximize neuroprotective but minimize neurotoxic effects of general anesthetics.
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Alzheimer's disease (AD) is the most common form of dementia and remains a growing worldwide health problem. As life expectancy continues to increase, the number of AD patients presenting for surgery and anesthesia will steadily rise. The etiology of sporadic AD is thought to be multifactorial, with environmental, biological and genetic factors interacting together to influence AD pathogenesis. ⋯ Tau pathology is important in AD as it correlates very well with cognitive dysfunction. Lately, several studies have begun to elucidate the mechanisms by which anesthetic exposure might affect the phosphorylation, aggregation and function of this microtubule-associated protein. Here, we specifically review the literature detailing the impact of anesthetic administration on aberrant tau hyperphosphorylation as well as the subsequent development of neurofibrillary pathology and degeneration.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Dec 2013
ReviewAnesthesia, surgery, illness and Alzheimer's disease.
Patients and their families have, for many decades, detected subtle changes in cognition subsequent to surgery, and only recently has this been subjected to scientific scrutiny. Through a combination of retrospective human studies, small prospective biomarker studies, and experiments in animals, it is now clear that durable consequences of both anesthesia and surgery occur, and that these intersect with the normal processes of aging, and the abnormal processes of chronic neurodegeneration. It is highly likely that inflammatory cascades are at the heart of this intersection, and if confirmed, this suggests a therapeutic strategy to mitigate enhanced neuropathology in vulnerable surgical patients.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Dec 2013
ReviewHereditary vulnerabilities to post-operative cognitive dysfunction and dementia.
In view of multiple prospective investigations reporting an incidence of 10% or greater in elderly patients after cardiac and non-cardiac procedures, it is surprising that no families, twins or even individual cases have been reported with persistent post-operative cognitive dysfunction (POCD) or post-operative dementia (POD) that is otherwise unexplained. As POCD and POD research has shifted in recent years from surgical and anesthetic variables to predictors of intrinsic, patient-specific susceptibility, a number of markers based on DNA sequence variation have been investigated. Nevertheless, no heritable, genomic indices of persistent POCD or post-operative dementia lasting 3 months or longer after surgery have been identified to date. The present manuscript surveys challenges confronting the search for markers of heritable vulnerability to POCD and POD, and proposes steps forward to be taken now, including the addition of surgical and anesthetic descriptors to ongoing longitudinal dementia protocols and randomized clinical trials (RCTs) comprising serial psychometric testing, and a fresh focus on phenotypes and genotypes shared between outliers with "extreme" POCD and POD traits.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Dec 2013
ReviewA review of epidemiological evidence for general anesthesia as a risk factor for Alzheimer's disease.
Exposure to surgery and general anesthesia (GA) has been hypothesized to be a potential risk factor for the development of Alzheimer's disease (AD). Some basic science research studies have demonstrated AD pathology in animals following exposure to inhalational anesthetics. However, controversy exists as to whether GA is associated with an elevated risk of developing AD in human populations. ⋯ A limited number of retrospective cohort studies have likewise not provided definitive information supporting an association. Therefore, at the present time there is limited information to support the hypothesis of AD developing as a consequence of GA, although there are few high quality studies in this area. Given the high prevalence and impact of AD, and the relatively frequent exposure of large populations to surgical procedures, the association between AD and GA requires further study.