Laminin 925-933 receptor In a working group exposed month ol
In 2008, a working group exposed 12-month-old transgenic mice (mutation for human amyloid precursor protein expression) and their non-transgenic littermates to isoflurane and halothane for 120min per day for five days. It was concluded that in the transgenic mouse there was overload of amyloid protein plaques after halothane use and tau protein aggregation after exposure to isoflurane. However, no change in cognitive performance was found in mutant mice, no effect of volatile anesthetics on apoptosis was found in either the transgenic or control mice, and there was no dissociation between amyloid generation (halothane – mutant mice) versus decline of cognitive performance (isoflurane – control mice). Later, with the same mice model, the animals were exposed to isoflurane for 20–30min twice weekly for three months and were found to exhibit behavioral decrease and increased mortality. Similar responses to Alzheimer disease were also identified in transgenic mice, such as increased numbers of apoptotic cells, reduced autophagy, reduced astroglia and increased microglia response, as well as increased amyloid protein aggregates.
In 2011, a study using triple-mutated mice models for Alzheimer disease exposed one group to general anesthesia with halothane or isoflurane 5h a week for four weeks (at three different ages: 2, 4, and 6 months) and another had no exposure to inhaled anesthetics. No differences were found in cognitive decline of mutant mice exposed to volatile anesthetics compared to mutant mice that were not exposed. Although phosphorylated tau protein levels were increased in the hippocampus two months after surgery, no amyloid, caspase, microglia, or synaptophysin changes were found. These results appeared to indicate that exposure to these inhalational agents during the pre-symptomatic Laminin 925-933 receptor of Alzheimer disease is not related to cognitive decline acceleration.
Intravenous anesthetic agents, particularly propofol, are also associated with increased tau protein in rat hippocampus, and this effect appears to be due to a direct action of the drug and not to secondary physiological effects (such as hypothermia).
The presence of cognitive decline after surgery is reasonably well established and there are many animal studies examining this interaction. Post-surgical cognitive decline in aged mice has been associated with microgliosis, amyloid protein production, and tau protein hyperphosphorylation in the hippocampus. The role of neuroinflammation in post-surgical cognitive dysfunction and its relation to Alzheimer disease has also been studied. In wild type young mice, surgery, not anesthesia, caused neuroinflammation and acute cognitive losses, and both microgliosis and cognitive deficits were reduced by antiinflammatory agents.35, 36, 37 Surgery leads to the formation of tumor necrosis factor-α, which causes damage to the blood-brain barrier and allows the infiltration of inflammatory macrophages, especially in the hippocampus. Mice undergoing surgery compared to mice that were only anesthetized without undergoing any surgical intervention had increased levels of interleukin-1β and interleukin-6.
Science and scientific investigation in this area did not stagnate and as early as 2008 there was a study that supported the low concentrations of amyloid as a potential neurotransmitter modulating role, which contradicted the guilty attitude of the scientific community in general.
Currently New studies have emerged in this area. A prospective longitudinal study of 2016 involved first-time coronary bypass patients who were initially enrolled in a cognitive outcome comparison study after randomization to receive either low or high doses of fentanyl. After 12-month evaluation, the same patients were invited to participate in a follow-up study at 7.5 years after surgery. Of the 326 initial patients, aged 55 years or over, 193 were assessed. Patients were evaluated for development of dementia and postoperative cognitive dysfunction was also investigated at three months, 12 months, and 7.5 years after surgery. However, it was only possible to evaluate 113 patients for both dementia and postoperative cognitive dysfunction. At 7.5 years after surgery, the prevalence of dementia was 30.8% in patients aged over 55 years at the time of intervention. The authors attribute this high prevalence of dementia to anesthesia/surgery or the natural decline of cognitive abilities with aging and in patients with severe cardiovascular disease. They add that since there was no follow-up of a non-surgical control group, this will be an important limitation of the study. Postoperative cognitive dysfunction was detected in 32.8%. Of the 113 patients evaluated for both entities, 44% of those with dementia were also classified with postoperative cognitive dysfunction. Pre-existing cognitive deficit and peripheral vascular disease were both associated with dementia at 7.5 years after coronary artery bypass, and postoperative cognitive dysfunction at either three or eight months was associated with increased mortality at 7.5 years.