Effects of anesthesia on cerebral blood flow, metabolism, and neuroprotection

Slupe, Andrew M.; Kirsch, Jeffrey R.

doi:10.1177/0271678x18789273

Cited by 235 publications

(224 citation statements)

References 265 publications

(282 reference statements)

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“…In this study, OCT and TPM imaging were only performed in the cortex of mice due to the relatively shallow imaging depth of these modalities. Notably, the effect of isoflurane should also be considered, as it may induce capillary stalling, as previously reported 4,44 . Nevertheless, our results clearly show the significant alterations in the microcirculation of SVaD mice compared to control.…”

Section: Discussionmentioning

confidence: 83%

Increased capillary stalling is associated with endothelial glycocalyx loss in subcortical vascular dementia

Yoon

Shin

et al. 2020

Preprint

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Proper regulation and patency of cerebral microcirculation is crucial for maintaining a healthy brain. Capillary stalling, i.e., the brief interruption of microcirculation mainly by leukocytes, has been observed in several diseases and contributes to disease pathogenesis or progression. However, the underpinning mechanism for leukocyte capillary plugging remains elusive. Therefore, we investigated the mechanism of capillary stalling in mice during the development of subcortical vascular dementia (SVaD), the most common type of vascular dementia characterized by impaired microcirculation and associated pathological features. Longitudinal optical coherence tomography angiography showed increased number of stalled segments as the disease progressed, while two-photon microscopy indicated a less extensive endothelial glycocalyx (EG) in the stalled segments. We also found that increased gliosis and blood-brain barrier leakage were correlated with the increased number of stalled segments. Based on the above, we conclude that EG potentially mediates capillary stalling and can be a therapeutic target of SVaD.

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Section: Discussionmentioning

confidence: 83%

Increased capillary stalling is associated with endothelial glycocalyx loss in subcortical vascular dementia

Yoon

Shin

et al. 2020

Preprint

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“…As the tracer gets trapped, animals can be later anesthetized for the scan without in uencing uptake. Thus, differences in these studies may be due to alterations of cerebral blood ow and SE and the inhibition of convulsions due to the use of anesthesia [8].…”

Section: Discussionmentioning

confidence: 99%

“…Perfusion-weighted magnetic resonance imaging (MRI) may be used to investigate perfusion changes during SE in patients or animal models [7], but needs to be performed under general anesthesia during data acquisition to immobilize the subject. As anesthesia is known to in uence brain perfusion [8], this most probably in uences study outcome.…”

Section: Introductionmentioning

confidence: 99%

99mTc-HMPAO SPECT imaging reveals brain hypoperfusion during status epilepticus

Bascuñana

Wolf

Jahreis

et al. 2020

Preprint

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Status epilepticus (SE) is a clinical emergency with high mortality. SE can trigger neuronal death or injury and alteration of neuronal networks resulting in long-term cognitive decline or epilepsy. Among the multiple factors contributing to this damage, imbalance between oxygen and glucose requirements and brain perfusion during SE has been proposed. Herein, we aimed to quantify by neuroimaging the spatiotemporal course of brain perfusion during and after lithium-pilocarpine-induced SE in rats. To this purpose, animals underwent 99mTc-HMPAO SPECT imaging at different time points during and after SE using a small animal SPECT/CT system. 99mTc-HMPAO regional uptake was normalized to the injected dose. In addition, voxel-based statistical parametric mapping was performed. SPECT imaging showed an increase of cortical perfusion before clinical seizure activity onset followed by regional hypo-perfusion starting with the first convulsive seizure and during SE. Twenty-four hours after SE, brain 99mTc-HMPAO uptake was widely decreased. Finally, chronic epileptic animals showed regionally decreased perfusion affecting hippocampus and cortical sub-regions. Despite elevated energy and oxygen requirements, brain hypo-perfusion is present during SE. Our results suggest that insufficient compensation of required blood flow might contribute to the neuronal damage and neuroinflammation, and ultimately to chronic epilepsy generated by SE.

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“…A major complication for translation in preclinical studies is the use of anesthetics. Anesthetics have effects not only in vasodilation or perfusion [239] but also on receptor binding in the brain [240][241][242]. Animal brain receptor experiments are often performed under anesthesia due to the difficulty or impossibility of training an animal to remain immobile during the scan.…”

Section: Quantitative Receptor Imaging In Clinical Translationmentioning

confidence: 99%

Quantitative Rodent Brain Receptor Imaging

et al. 2019

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Positron emission tomography (PET) is a non-invasive imaging technology employed to describe metabolic, physiological, and biochemical processes in vivo. These include receptor availability, metabolic changes, neurotransmitter release, and alterations of gene expression in the brain. Since the introduction of dedicated small-animal PET systems along with the development of many novel PET imaging probes, the number of PET studies using rats and mice in basic biomedical research tremendously increased over the last decade. This article reviews challenges and advances of quantitative rodent brain imaging to make the readers aware of its physical limitations, as well as to inspire them for its potential applications in preclinical research. In the first section, we briefly discuss the limitations of small-animal PET systems in terms of spatial resolution and sensitivity and point to possible improvements in detector development. In addition, different acquisition and post-processing methods used in rodent PET studies are summarized. We further discuss factors influencing the test-retest variability in small-animal PET studies, e.g., different receptor quantification methodologies which have been mainly translated from human to rodent receptor studies to determine the binding potential and changes of receptor availability and radioligand affinity. We further review different kinetic modeling approaches to obtain quantitative binding data in rodents and PET studies focusing on the quantification of endogenous neurotransmitter release using pharmacological interventions. While several studies have focused on the dopamine system due to the availability of several PET tracers which are sensitive to dopamine release, other neurotransmitter systems have become more and more into focus and are described in this review, as well. We further provide an overview of latest genome engineering technologies, including the CRISPR/Cas9 and DREADD systems that may advance our understanding of brain disorders and function and how imaging has been successfully applied to animal models of human brain disorders. Finally, we review the strengths and opportunities of simultaneous PET/magnetic resonance imaging systems to study drug-receptor interactions and challenges for the translation of PET results from bench to bedside.aligned to a standard reference space for several PET radioligands [63,64]. This enables the use of an automatic normalization and the application of predefined VOIs, minimizing the user-dependent variability. This is particularly important in small-animal PET brain studies, if a voxelbased analysis is performed and small deviations from the standard space will largely impact the results.Quantification Accuracy: Partial-Volume Effect, Spillover, Mass Effect, and Data Reproducibility

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Effects of anesthesia on cerebral blood flow, metabolism, and neuroprotection

Cited by 235 publications

References 265 publications

Increased capillary stalling is associated with endothelial glycocalyx loss in subcortical vascular dementia

Increased capillary stalling is associated with endothelial glycocalyx loss in subcortical vascular dementia

99mTc-HMPAO SPECT imaging reveals brain hypoperfusion during status epilepticus

Quantitative Rodent Brain Receptor Imaging

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