“…Mounting clinical and experimental evidence indicates that reactive oxygen species and reactive nitrogen species (eg nitric oxide, NO[*]) play important roles in many physiological and pathological conditions, resulting in oxidative stress, an important mediator of damage to cell structures, including lipids and membranes, proteins, and DNA . The brain is particularly susceptible because it has a large lipid content of myelin sheaths, a high rate of brain oxidative metabolism, and a low antioxidant capacity . Data suggest that oxidative stress and/or antioxidant deficiencies may increase the damage to cerebral tissue, leading to cognitive decline and possibly irreversible cerebral degeneration, potentially leading to the development of persistent delirium …”
The systems integration failure hypothesis attempts to explain how the various proposed delirium pathophysiologic theories interact with each other, causing various clinically observed delirium phenotypes. A better understanding of the underlying pathophysiology of delirium may eventually assist in designing better prevention and management approaches.
“…Mounting clinical and experimental evidence indicates that reactive oxygen species and reactive nitrogen species (eg nitric oxide, NO[*]) play important roles in many physiological and pathological conditions, resulting in oxidative stress, an important mediator of damage to cell structures, including lipids and membranes, proteins, and DNA . The brain is particularly susceptible because it has a large lipid content of myelin sheaths, a high rate of brain oxidative metabolism, and a low antioxidant capacity . Data suggest that oxidative stress and/or antioxidant deficiencies may increase the damage to cerebral tissue, leading to cognitive decline and possibly irreversible cerebral degeneration, potentially leading to the development of persistent delirium …”
The systems integration failure hypothesis attempts to explain how the various proposed delirium pathophysiologic theories interact with each other, causing various clinically observed delirium phenotypes. A better understanding of the underlying pathophysiology of delirium may eventually assist in designing better prevention and management approaches.
“…It is known that tissue damage resulting from surgery activates the peripheral innate immune system leading to activation of the cytokine cascade and the release of many inflammatory mediators including oxygen free radicals, arachadonic acid metabolites, cytokines, nitric oxide and endothelins (Giannoudis et al, 2006;Karlidag et al, 2006;Levy and Tanaka, 2003;Lin et al, 2000). However, it is not yet known if a peripheral immune response to surgical trauma results in an exaggerated neuroinflammatory response in the aged brain.…”
Following surgery, elderly patients often suffer from postoperative cognitive dysfunction (POCD) which can persist long after physical recovery. It is known that surgery-induced tissue damage activates the peripheral innate immune system resulting in the release of inflammatory mediators. Compared to adults, aged animals demonstrate increased neuroinflammation and microglial priming that leads to an exaggerated proinflammatory cytokine response following activation of the peripheral immune system. Therefore, we sought to determine if the immune response to surgical trauma results in increased neuroinflammation and cognitive impairment in aged mice. Adult and aged mice underwent minor abdominal surgery and 24 h later hippocampal cytokines were measured and working memory was assessed in a reversal learning version of the Morris water maze. While adult mice showed no signs of neuroinflammation following surgery, aged mice had significantly increased levels of IL-1β mRNA in the hippocampus. Minor surgery did not result in severe cognitive impairment although aged mice that underwent surgery did tend to perseverate in the old target during reversal testing suggesting reduced cognitive flexibility. Overall these results suggest that minor surgery leads to an exaggerated neuroinflammatory response in aged mice but does not result in significantly impaired performance in the Morris water maze.
“…Immune activation, oxidative stress, and disturbances of cerebral neurotransmitters due to serious illness and the process of aging have all been implicated in the pathogenesis of delirium …”
Preoperatively high neopterin levels predicted delirium after cardiac surgery in older adults, in addition to the well-known risk factors of poor cognitive function, high cardio-surgical risk, and combined CABG and valve surgery. Postoperative neopterin and HVA levels were also found to be associated with delirium, together with preoperative cognitive functioning. Plasma neopterin may be a candidate biomarker for delirium after cardiac surgery in these older adults.
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