Inhaled Anesthetic Potency in Aged Alzheimer Mice

Bianchi, Shannon L.; Caltagarone, Breanna M.; LaFerla, Frank M.; Eckenhoff, Roderic G.; Kelz, Max B.

doi:10.1213/ane.0b013e3181b5a292

Cited by 21 publications

(19 citation statements)

References 16 publications

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“…We started the study with approximately equal numbers of mice in all groups (≥10), but had significant mortality in the DMSO- and dantrolene-treated groups when they underwent surgery for the Alzet pump replacement, primarily during the anesthetic induction. Excess mortality in this transgenic animal has been documented before [2]. This suggests that, given the loss of nearly the same number of vehicle and dantrolene treated animals, the 3xTg-AD mouse model may be more vulnerable to the effects of anesthesia.…”

mentioning

confidence: 67%

Dantrolene ameliorates cognitive decline and neuropathology in Alzheimer triple transgenic mice

Peng

Inan

et al. 2012

Neuroscience Letters

103

115

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Disruption of intracellular calcium homeostasis via abnormal and excessive activation of ryanodine receptors plays an important role in the neuropathology of Alzheimer’s disease. We investigated the therapeutic effect of dantrolene, a ryanodine receptor antagonist, on cognitive dysfunction and neuropathology in the triple transgenic Alzheimer mouse model (3xTg-AD). 3xTg-AD mice were treated with dantrolene from 2 to 13 months of age. Learning and memory were measured with the Morris Water Maze at 6, 10, and 13 months of age. Amyloid and tau neuropathology and biomarkers for synaptic dysfunction and neurodegeneration were examined in the brain using immunoblotting or immunohistochemistry. Dantrolene treatment for 11 months significantly reduced both memory deficits and amyloid plaque load in the hippocampus in 13 month old 3xTg-AD mice. Dantrolene treatment, however, had no effect on phosphorylated tau, phosphorylated or total GSK-3β, synaptic markers, or mitochondrial or cytosolic cytochrome C. Our results suggest that dantrolene significantly improves cognition in a murine model of Alzheimer’s disease and is associated with a reduction in amyloid plaque burden, forming the basis for a novel therapeutic approach for Alzheimer’s disease.

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mentioning

confidence: 67%

Dantrolene ameliorates cognitive decline and neuropathology in Alzheimer triple transgenic mice

Peng

Inan

et al. 2012

Neuroscience Letters

103

115

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“…1). Recent studies have shown different sensitivity of inhaled anesthetics in transgenic models of AD (Bianchi et al, 2010). We did not find any difference in anesthetic sensitivity in control and AD rats.…”

Section: Discussionmentioning

confidence: 99%

Functional MRI and neural responses in a rat model of Alzheimer's disease

et al. 2013

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Based on the hypothesis that brain plaques and tangles can affect cortical functions in Alzheimer's disease (AD) and thus modify functional activity, we investigated functional responses in an AD rat model (called the Samaritan Alzheimer’s rat achieved by ventricular infusion of amyloid peptide) and age-matched healthy control. High-field functional magnetic resonance imaging (fMRI) and extracellular neural activity measurements were applied to characterize sensory-evoked responses. Electrical stimulation of the forepaw led to BOLD and neural responses in the contralateral somatosensory cortex and thalamus. In AD brain we noted much smaller BOLD activation patterns in the somatosensory cortex (i.e., about 50% less activated voxels compared to normal brain). While magnitudes of BOLD and neural responses in the cerebral cortex were markedly attenuated in AD rats compared to normal rats (by about 50%), the dynamic coupling between the BOLD and neural responses in the cerebral cortex, as assessed by transfer function analysis, remained unaltered between the groups. However thalamic BOLD and neural responses were unaltered in AD brain compared to controls. Thus cortical responses in the AD model were indeed diminished compared to controls, but the thalamic responses in the AD and control rats were quite similar. Therefore these results suggest that Alzheimer’s disease may affect cortical function more than subcortical function, which may have implications for interpreting altered human brain functional responses in fMRI studies of Alzheimer’s disease.

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“…However, this may be difficult, since the minimal alveolar concentration values for animal models of AD are increased relative to their non-AD counterparts. 59,60 Although a recent study did not find an association between depth of anesthesia and development of POCD, 61 further research is certainly needed. Use of regional anesthesia instead of general anesthesia has been suggested to avoid volatile anesthetic exposure.…”

Section: Do We Need To Change Clinical Practice?mentioning

confidence: 99%

Brief review: Anesthetic neurotoxicity in the elderly, cognitive dysfunction and Alzheimer’s disease

Bittner

Yue

Xie

2010

Can J Anesth/J Can Anesth

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Purpose Postoperative cognitive decline in the elderly has emerged as a major health concern. In addition, there is a growing interest in the potential relationship between general anesthetic exposure and the onset and progression of Alzheimer’s disease (AD). The available evidence of a possible association between anesthesia, surgery, and long-term cognitive effects, including AD, deserves consideration. In this review, we summarize the evidence for anesthesia-induced neurotoxicity in the elderly, while highlighting the limitations of existing data, and we put the literature into perspective for the clinician. Principal findings A growing body of evidence suggests that general anesthetics may be neurotoxic to both young and aging brains. Much of the evidence originates from in vitro and in vivo studies with cells, rodents, and nonhuman primates. Despite the animal data suggesting a relationship between anesthesia and neurotoxicity in the elderly, a definitive link remains elusive in humans. Conclusions The possible relation between anesthetic neurotoxicity, postoperative cognitive dysfunction, and AD remains elusive. It remains unclear whether postoperative cognitive decline in the elderly is related more to perioperative stress and related medical co-morbidities.

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Inhaled Anesthetic Potency in Aged Alzheimer Mice

Cited by 21 publications

References 16 publications

Dantrolene ameliorates cognitive decline and neuropathology in Alzheimer triple transgenic mice

Dantrolene ameliorates cognitive decline and neuropathology in Alzheimer triple transgenic mice

Functional MRI and neural responses in a rat model of Alzheimer's disease

Brief review: Anesthetic neurotoxicity in the elderly, cognitive dysfunction and Alzheimer’s disease

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