Objective Previous research suggests a link between anesthetic exposure and Alzheimer’s disease exists. Since anesthetics are rarely given alone, we ask whether addition of surgery further modulates Alzheimer’s disease. Background Cognitive dysfunction occurs after surgery in humans. Anesthesia alone produces cognitive decline in both older wild-type mice and rats, and the addition of surgery produces transient decline in young adult wild type mice. Because neuroinflammation has been implicated, and occurs early in Alzheimer’s disease, we hypothesize that the neuroinflammatory stress associated with surgery will accelerate the progression of Alzheimer’s disease. Methods Cecal ligation and excision was performed on pre-symptomatic 5–11 month-old triple-transgenic Alzheimer (3xTgAD) and C57BL/6 wild type mice under desflurane anesthesia. Surgery animals were compared to aged matched 3xTgAD and WT mice exposed to air or desflurane alone. Cognitive function was assessed via Morris water maze at 2 and 13 weeks post-operatively. Amyloid and tau pathology, as well as inflammation and synaptic markers were quantified with immunohistochemistry, Luminex, ELISA or western blot assays. Results A significant cognitive impairment in 3xTgAD mice that underwent surgery compared with air or desflurane controls, persisted to at least 14 weeks after surgery. Microglial activation, amyloidopathy and tauopathy were enhanced by surgery as compared to desflurane alone. No differences between surgery, anesthetic or air controls were detected in WT mice Conclusions Surgery causes a durable increment in Alzheimer pathogenesis, primarily through a transient activation of neuroinflammation.

Background Experimental evidence suggests that anesthetics accelerate symptomatic neurodegenerative disorders like Alzheimer disease (AD). Since AD pathology precedes symptoms, we asked whether anesthetic exposure in the presymptomatic interval accelerates neuropathology and appearance of symptoms. Methods Triple transgenic Alzheimer mice exposed to the general aesthetics, halothane or isoflurane, at 2, 4 and 6 months of age, underwent water maze cognitive testing two months afterwards and their brains subsequently analyzed with ELISA, immunoblots, and immunohistochemistry for amyloid and tau pathology and biomarkers. Results Learning and memory improved after halothane exposure in the 2 month old group relative to controls, but no changes were noted in any isoflurane group. When gender was examined in all age groups, females exposed to halothane performed better than females exposed to isoflurane or controls. Thus, improvement in the 2 month exposure group is most likely due to a gender effect. Phospho-tau in the hippocampus was significantly increased two months after anesthesia, especially in the 6 month exposure group but changes in amyloid, caspase, microglia or synaptophysin were not detected. Conclusions These results indicate that exposure to two different inhalational anesthetics during the presymptomatic period of AD does not accelerate cognitive decline, two months later, and may cause a stress response, marked by hippocampal phosphorylated tau, resulting in preconditioning against the ongoing neuropathology, primarily in female mice.

BACKGROUND Multiple lines of evidence suggest that the adrenergic system can modulate sensitivity to anesthetic-induced immobility and anesthetic-induced hypnosis as well. However, several considerations prevent the conclusion that the endogenous adrenergic ligands norepinephrine and epinephrine alter anesthetic sensitivity. METHODS Using dopamine β-hydroxylase (Dbh−/−) mice genetically engineered to lack the adrenergic ligands and their siblings with normal adrenergic levels, we test the contribution of the adrenergic ligands upon volatile anesthetic induction and emergence. Moreover, we investigate the effects of intravenous dexmedetomidine in adrenergic-deficient mice and their siblings using both righting reflex and processed electroencephalographic measures of anesthetic hypnosis. RESULTS We demonstrate that the loss of norepinephrine and epinephrine and not other neuromodulators copackaged in adrenergic neurons is sufficient to cause hypersensitivity to induction of volatile anesthesia. However, the most profound effect of adrenergic deficiency is retarding emergence from anesthesia, which takes two to three times as long in Dbh−/− mice for sevoflurane, isoflurane, and halothane. Having shown that Dbh−/− mice are hypersensitive to volatile anesthetics, we further demonstrate that their hypnotic hypersensitivity persists at multiple doses of dexmedetomidine. Dbh−/− mice exhibit up to 67% shorter latencies to loss of righting reflex and up to 545% longer durations of dexmedetomidine-induced general anesthesia. Central rescue of adrenergic signaling restores control-like dexmedetomidine sensitivity. A novel continuous electroencephalographic analysis illustrates that the longer duration of dexmedetomidine-induced hypnosis is not due to a motor confound, but occurs because of impaired anesthetic emergence. CONCLUSIONS Adrenergic signaling is essential for normal emergence from general anesthesia. Dexmedetomidine-induced general anesthesia does not depend upon inhibition of adrenergic neurotransmission.

Carbon monoxide (CO) exposure at high concentrations results in overt neurotoxicity. Exposure to low CO concentrations occurs commonly yet is usually sub-clinical. Infants are uniquely vulnerable to a variety of toxins, however, the effects of postnatal sub-clinical CO exposure on the developing brain are unknown. Apoptosis occurs normally within the brain during development and is critical for synaptogenesis. Here we demonstrate that brief, postnatal sub-clinical CO exposure inhibits developmental neuroapoptosis resulting in impaired learning, memory, and social behavior. Three hour exposure to 5 ppm or 100 ppm CO impaired cytochrome c release, caspase-3 activation, and apoptosis in neocortex and hippocampus of 10 day old CD-1 mice. CO increased NeuN protein, neuronal numbers, and resulted in megalencephaly. CO-exposed mice demonstrated impaired memory and learning and reduced socialization following exposure. Thus, CO-mediated inhibition of neuroapoptosis might represent an important etiology of acquired neurocognitive impairment and behavioral disorders in children.

Sparging causes platelets to bind to air bubbles and each other. Surfactants added before sparging attenuate platelet-bubble and platelet-platelet binding. Surfactants may have a clinical role in attenuating gas embolism-induced platelet-bubble and platelet-platelet binding.