Neuroinflammation increases oxygen extraction in a mouse model of Alzheimer’s disease DOI Open Access
Chang Liu, Alfredo Cárdenas‐Rivera,

Shayna Teitelbaum

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Окт. 19, 2023

Neuroinflammation, impaired metabolism, and hypoperfusion are fundamental pathological hallmarks of early Alzheimer's disease (AD). Numerous studies have asserted a close association between neuroinflammation disrupted cerebral energetics. During AD progression other neurodegenerative disorders, persistent state chronic reportedly exacerbates cytotoxicity potentiates neuronal death. Here, we assessed the impact neuroinflammatory challenge on metabolic demand microvascular hemodynamics in somatosensory cortex an mouse model. We utilized vivo 2-photon microscopy phosphorescent oxygen sensor Oxyphor 2P to measure partial pressure (pO2) capillary red blood cell flux cortical microvessels awake mice. Intravascular pO2 RBC measurements were performed 8-month-old APPswe/PS1dE9 mice wildtype littermates days 0, 7, 14 14-day period lipopolysaccaride-induced neuroinflammation. Before induced inflammatory challenge, demonstrated reduced but similar as their wild type counterparts. Neuroinflammation provoked significant reductions intravascular levels elevated extraction both animal groups, without significantly altering capillaries. This study provides evidence that alters at stages substantially vascular supply. The results will guide our understanding neuroinflammation's influence neuroimaging biomarkers for diagnosis.

Язык: Английский

Cerebral oxygen extraction fractionMRI: Techniques and applications DOI Open Access
Dengrong Jiang, Hanzhang Lu

Magnetic Resonance in Medicine, Год журнала: 2022, Номер 88(2), С. 575 - 600

Опубликована: Май 5, 2022

The human brain constitutes 2% of the body's total mass but uses 20% oxygen. rate brain's oxygen utilization can be derived from a knowledge cerebral blood flow and extraction fraction (OEF). Therefore, OEF is key physiological parameter function metabolism. has been suggested to useful biomarker in number diseases. With recent advances MRI techniques, several MRI‐based methods have developed measure brain. These techniques are based on T 2 blood, signal phase, magnetic susceptibility blood‐containing voxels, effect deoxyhemoglobin behavior extravascular tissue, calibration BOLD using gas inhalation. Compared 15 O PET, which considered “gold standard” for measurement, non‐invasive, radiation‐free, more widely available. This article provides review these emerging techniques. We first briefly introduce role homeostasis. then methodological aspects different categories including their mechanisms, acquisition methods, data analyses. strengths limitations discussed. Finally, we applications pathological conditions.

Язык: Английский

Процитировано

46
Non-contrast assessment of blood-brain barrier permeability to water in mice: An arterial spin labeling study at cerebral veins DOI Creative Commons
Zhiliang Wei, Hongshuai Liu, Zixuan Lin

и другие.

NeuroImage, Год журнала: 2023, Номер 268, С. 119870 - 119870

Опубликована: Янв. 11, 2023

Blood-brain barrier (BBB) plays a critical role in protecting the brain from toxins and pathogens. However, vivo tools to assess BBB permeability are scarce often require use of exogenous contrast agents. In this study, we aimed develop non-contrast arterial-spin-labeling (ASL) based MRI technique estimate water mice. By determining relative fraction labeled spins that were exchanged into tissue as opposed those remained cerebral veins, estimated indices global including extraction (E) surface-area product (PS). First, using multiple post-labeling delay ASL experiments, bolus arrival time (BAT) reach great vein Galen (VG) be 691.2 ± 14.5 ms (N = 5). Next, investigated dependence VG signal on labeling duration identified an optimal imaging protocol with 1200 PLD 100 ms. Quantitative E PS values wild-type mice found 59.9 3.2% 260.9 18.9 ml/100 g/min, respectively. contrast, Huntington's disease (HD) revealed significantly higher (69.7 2.4%, P 0.026) (318.1 17.1 0.040), suggesting breakdown mouse model. Reproducibility studies coefficient-of-variation (CoV) 4.9 1.7% 6.1 1.2% for PS, The proposed method may open new avenues preclinical research pathophysiological mechanisms diseases therapeutic trials animal models.

Язык: Английский

Процитировано

23
Elevated PDGF‐BB from Bone Impairs Hippocampal Vasculature by Inducing PDGFRβ Shedding from Pericytes DOI Creative Commons
Guanqiao Liu, Jiekang Wang, Zhiliang Wei

и другие.

Advanced Science, Год журнала: 2023, Номер 10(20)

Опубликована: Апрель 27, 2023

Evidence suggests a unique association between bone aging and neurodegenerative/cerebrovascular disorders. However, the mechanisms underlying bone-brain interplay remain elusive. Here platelet-derived growth factor-BB (PDGF-BB) produced by preosteoclasts in is reported to promote age-associated hippocampal vascular impairment. Aberrantly elevated circulating PDGF-BB aged mice high-fat diet (HFD)-challenged correlates with capillary reduction, pericyte loss, increased blood-brain barrier (BBB) permeability their hippocampus. Preosteoclast-specific Pdgfb transgenic markedly high plasma concentration faithfully recapitulate BBB impairment cognitive decline. Conversely, preosteoclast-specific knockout have attenuated or HFD-challenged mice. Persistent exposure of brain pericytes concentrations upregulates matrix metalloproteinase 14 (MMP14), which promotes ectodomain shedding PDGF receptor β (PDGFRβ) from surface. MMP inhibitor treatment alleviates loss reduction conditional antagonizes leakage The findings establish role bone-derived mediating disruption identify ligand-induced PDGFRβ as feedback mechanism for downregulation consequent loss.

Язык: Английский

Процитировано

23
The impact of isoflurane anesthesia on brain metabolism in mice: An MRI and electroencephalography study DOI
Zhiliang Wei, Seung‐Eon Roh,

Xiuli Yang

и другие.

NMR in Biomedicine, Год журнала: 2024, Номер unknown

Опубликована: Сен. 10, 2024

Abstract Isoflurane is one of the most widely used anesthetic agents in rodent imaging studies. However, impact isoflurane on brain metabolism has not been fully characterized to date, primarily due a scarcity noninvasive technologies quantitatively measure brain's metabolic rate vivo. In this study, using noncontrast MRI techniques, we dynamically measured cerebral oxygen (CMRO 2 ) under varying doses anesthesia mice. Concurrently, systemic parameters heart and respiration rates were recorded alongside CMRO . Additionally, electroencephalogram (EEG) recording was identify changes neuronal activities same regimen employed experiments. We found suppression by dose‐dependent manner, concomitant with diminished high‐frequency EEG activity. The degree strongly correlated rate, which offers potential approach calibrate measurements. Furthermore, level associated neural responses somatosensory motor cortices mice estimated as 308.2 μmol/100 g/min. These findings may facilitate integration into future studies involving animal disease models usage.

Язык: Английский

Процитировано

6
Neuroinflammation increases oxygen extraction in a mouse model of Alzheimer’s disease DOI Creative Commons
Chang Liu, Alfredo Cárdenas‐Rivera,

Shayna Teitelbaum

и другие.

Alzheimer s Research & Therapy, Год журнала: 2024, Номер 16(1)

Опубликована: Апрель 10, 2024

Neuroinflammation, impaired metabolism, and hypoperfusion are fundamental pathological hallmarks of early Alzheimer's disease (AD). Numerous studies have asserted a close association between neuroinflammation disrupted cerebral energetics. During AD progression other neurodegenerative disorders, persistent state chronic reportedly exacerbates cytotoxicity potentiates neuronal death. Here, we assessed the impact neuroinflammatory challenge on metabolic demand microvascular hemodynamics in somatosensory cortex an mouse model.

Язык: Английский

Процитировано

5
Magnetic Resonance Imaging in Animal Models of Alzheimer’s Disease Amyloidosis DOI Open Access
Ruiqing Ni

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(23), С. 12768 - 12768

Опубликована: Ноя. 25, 2021

Amyloid-beta (Aβ) plays an important role in the pathogenesis of Alzheimer’s disease. Aberrant Aβ accumulation induces neuroinflammation, cerebrovascular alterations, and synaptic deficits, leading to cognitive impairment. Animal models recapitulating pathology, such as transgenic, knock-in mouse rat models, have facilitated understanding disease mechanisms development therapeutics targeting Aβ. There is a rapid advance high-field MRI small animals. Versatile magnetic resonance imaging (MRI) sequences, diffusion tensor imaging, arterial spin labeling, resting-state functional MRI, anatomical MR spectroscopy, well contrast agents, been developed for preclinical animal models. These tools enabled high-resolution vivo structural, functional, molecular readouts with whole-brain field view. has used visualize non-invasively deposits, regional brain atrophy, impairment white matter integrity, connectivity, glymphatic system amyloidosis. Many are translational toward clinical applications patients In this review, we summarize recent advances visualizing pathophysiology amyloidosis We discuss outstanding challenges using animals propose future outlook Aβ-related alterations brains

Язык: Английский

Процитировано

27
Neuroimaging of Mouse Models of Alzheimer’s Disease DOI Creative Commons
Amandine Jullienne,

Michelle V. Trinh,

André Obenaus

и другие.

Biomedicines, Год журнала: 2022, Номер 10(2), С. 305 - 305

Опубликована: Янв. 28, 2022

Magnetic resonance imaging (MRI) and positron emission tomography (PET) have made great strides in the diagnosis our understanding of Alzheimer’s Disease (AD). Despite knowledge gained from human studies, mouse models continue to play an important role deciphering cellular molecular evolution AD. MRI PET are now being increasingly used investigate neuroimaging features provide basis for rapid translation clinical setting. Here, we overview landscape as a prelude in-depth review preclinical mice. A broad range recapitulate certain aspects AD, but no single model simulates disease spectrum. We focused on two most popular models, 3xTg-AD 5xFAD summarized all known published data, including contrasting findings. The goal this is reader with framework guide future studies existing also highlight that could be improved increase rigor reproducibility studies.

Язык: Английский

Процитировано

19
Senolytic therapy preserves blood-brain barrier integrity and promotes microglia homeostasis in a tauopathy model DOI Creative Commons

Minmin Yao,

Zhiliang Wei,

Jonathan Scharff Nielsen

и другие.

Neurobiology of Disease, Год журнала: 2024, Номер unknown, С. 106711 - 106711

Опубликована: Окт. 1, 2024

Язык: Английский

Процитировано

4
Toward accurate cerebral blood flow estimation in mice after accounting for anesthesia DOI Creative Commons
Zhiliang Wei, Yuguo Li, Adnan Bibic

и другие.

Frontiers in Physiology, Год журнала: 2023, Номер 14

Опубликована: Апрель 12, 2023

Purpose: To improve the accuracy of cerebral blood flow (CBF) measurement in mice by accounting for anesthesia effects. Methods: The dependence CBF on dose and time was investigated simultaneously measuring respiration rate (RR) heart (HR) under four different anesthetic regimens. Quantitative measured a phase-contrast (PC) MRI technique. RR evaluated with mouse monitoring system (MouseOX) while HR determined using an ultrashort-TE sequence. CBF, RR, were recorded dynamically temporal resolution 1 min total 19 mice. Linear regression models used to investigate relationships among dose, HR. Results: all showed significant ( p < 0.0001). However, itself insufficient account variations physiological parameters, that they time-dependent change even constant dose. together can explain 52.6% measurements, which is greater than amount variance explained (32.4%). Based multi-parametric results, model proposed correct effects specifically CBFcorrected=CBF+0.58RR−0.41HR−32.66Dose . We also reported awake-state be 142.0 ± 8.8 mL/100 g/min, consistent model-predicted value. Conclusion: improved correction accounts rate,

Язык: Английский

Процитировано

9
Metabolic and vascular imaging markers for investigating Alzheimer’s disease complicated by sleep fragmentation in mice DOI Creative Commons
Xiaoning Han, Guanshu Liu, Sang‐Soo Lee

и другие.

Frontiers in Physiology, Год журнала: 2024, Номер 15

Опубликована: Сен. 20, 2024

Background Sleep problem is a common complication of Alzheimer’s disease (AD). Extensive preclinical studies have been performed to investigate the AD pathology. However, pathophysiological consequence complicated by sleep remains be further determined. Purpose To brain metabolism and perfusion in an mouse model problem, subsequently identify potential imaging markers better understand associated pathophysiology. Methods We examined oxygen extraction fraction (OEF), cerebral metabolic rate (CMRO 2 ), blood flow (CBF) using state-of-the-art MRI techniques cohort 5xFAD mice. Additionally, neuroinflammation, indicated activated microglia, was assessed histology techniques. fragmentation (SF) utilized as representative for problems. Results SF with significant increases OEF ( P = 0.023) CMRO 0.029), indicating state hypermetabolism. CBF showed genotype-by-sleep interaction effect 0.026), particularly deep regions such hippocampus thalamus. Neuroinflammation primarily driven genotype rather than SF, especially measurements. Conclusion These results suggest that measurements are promising studying co-pathogenesis SF.

Язык: Английский

Процитировано

3