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

Shayna Teitelbaum

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 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.

Language: Английский

Vascular and Metabolic Responses to Elevated Circulating PDGF-BB in Mice: A Multiparametric MRI Study DOI Creative Commons

Xiuli Yang,

Jiekang Wang, Yuguo Li

et al.

Published: Feb. 11, 2025

Article Vascular and Metabolic Responses to Elevated Circulating PDGF-BB in Mice: A Multiparametric MRI Study Xiuli Yang 1,†, Jiekang Wang 2,3,†, Yuguo Li 1,4, Mei Wan 2,3,*, Zhiliang Wei 1,4,* 1 Russell H. Morgan Department of Radiology Radiological Science, Johns Hopkins University School Medicine, Baltimore, MD 21205, USA 2 Orthopaedic Surgery, 3 Biomedical Engineering, 4 F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, * Correspondence: [email protected] (M.W.); [email protected] (Z.W.) † These authors contributed equally this work. Received: 20 November 2024; Revised: December Accepted: 22 January 2025; Published: 11 February 2025 Abstract: circulating platelet-derived growth factor-BB (PDGF-BB) has been implicated the development various aged-related pathologies is recognized as a potential pro-aging factor. Although numerous studies have explored pathological roles PDGF-BB/PDGFRβ signaling pathway, few investigations dissected its function neurofunctional responses elevated PDGF-BB, primarily because in-vivo measurements are generally required assess neurofunction. To address knowledge gap, we characterized vascular metabolic vivo using multiparametric non-invasive non-contrast techniques conditional Pdgfb transgenic mouse model (PdgfbcTG) at 6 months age. Results indicated that PdgfbcTG mice exhibited decreased cerebral blood flow (p = 0.025), oxygen extraction 0.002), increased rate 0.035), mirroring changes observed human aging. The change was significantly higher (≥200.3%) compared naturally aged mice. This study provides evidence accelerates neurovascular

Language: Английский

Citations

0
Vascular and Metabolic Responses to Elevated Circulating PDGF-BB in Mice: A Multiparametric MRI Study DOI

Xiuli Yang,

Jiekang Wang, Yuguo Li

et al.

Published: April 2, 2025

Elevated circulating platelet-derived growth factor-BB (PDGF-BB) has been implicated in various aged-related pathologies and, therefore, is recognized as a potential pro-aging factor. Despite extensive studies on the pathological characterizations centering PDGF-BB/PDGFRβ signaling alterations, there limited research neurofunctional responses to elevated PDGF-BB, primarily because in-vivo measurements are generally required for studying neurofunction. To address this knowledge gap, we characterized vascular and metabolic PDGF-BB vivo using multiparametric non-invasive non-contrast MRI techniques conditional Pdgfb transgenic mouse model (PdgfbcTG) at 6 months of age. We found that PdgfbcTG mice exhibited decreased cerebral blood flow (P = 0.025), oxygen extraction 0.002), increased rate 0.035), which replicated changes observed human aging. Compared naturally aged mice, change was prominently higher (≥ 200.3%). Our study provides evidence accelerates neurovascular

Language: Английский

Citations

0
Cell Type-Specific Contributions to Impaired Blood-Brain Barrier and Cerebral Metabolism in Presymptomatic 5XFAD Mice DOI

Minmin Yao,

Na Sun, Raleigh M. Linville

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
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

et al.

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 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.

Language: Английский

Citations

3
Magnetic Resonance Imaging in Tauopathy Animal Models DOI Creative Commons
Ruiqing Ni

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 13

Published: Jan. 25, 2022

The microtubule-associated protein tau plays an important role in tauopathic diseases such as Alzheimer's disease and primary tauopathies progressive supranuclear palsy corticobasal degeneration. Tauopathy animal models, transgenic, knock-in mouse rat recapitulating tauopathy have facilitated the understanding of mechanisms. Aberrant accumulation hyperphosphorylated contributes to synaptic deficits, neuroinflammation, neurodegeneration, leading cognitive impairment models. Recent advances molecular imaging using positron emission tomography (PET) magnetic resonance (MRI) provided valuable insights into time course pathophysiology High-field MRI has been applied for

Language: Английский

Citations

10
Quantitative cerebrovascular reactivityMRIin mice using acetazolamide challenge DOI
Zhiliang Wei,

Yuguo Li,

Xirui Hou

et al.

Magnetic Resonance in Medicine, Journal Year: 2022, Volume and Issue: 88(5), P. 2233 - 2241

Published: June 17, 2022

Purpose To develop a quantitative MRI method to estimate cerebrovascular reactivity (CVR) in mice. Methods We described an procedure measure cerebral vasodilatory response acetazolamide (ACZ), vasoactive agent previously used human clinical imaging. Vascular was determined by blood flow (CBF) measured with phase‐contrast or pseudo‐continuous arterial spin labeling MRI. Vasodilatory input intensity plasma ACZ level using high‐performance liquid chromatography. verified the source of CVR signal comparing injection phosphate‐buffered saline and noninjection experiments. Dose dependence feasibility regional measurement were also investigated. Results Cerebral revealed exponential increase following intravenous injection, time constant 1.62 min. In contrast, exhibited slow linear CBF increase, consistent gradual accumulation anesthetic agent, isoflurane, this study. When different doses, injections 30, 60, 120, 180 mg/kg yielded concentration ( p < 0.0001). On other hand, changes under these doses not from each = 0.50). The multiple postlabeling delays similar vascular responses at delay values. There difference 0.005), isocortex (0.81 ± 0.17%/[μg/ml]) showing higher than deep‐brain regions. Mice receiving lived for minimum 6 months after study without noticeable aberrant behavior appearance. Conclusions demonstrated proof‐of‐principle new mapping technique

Language: Английский

Citations

10
Senolytic therapy preserves blood-brain barrier integrity and promotes microglia homeostasis in a tauopathy model DOI Open Access

Minmin Yao,

Zhiliang Wei,

Jonathan Scharff Nielsen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 29, 2024

Abstract Cellular senescence, characterized by expressing the cell cycle inhibitory proteins, is evident in driving age-related diseases. Senescent cells play a crucial role initiation and progression of tau-mediated pathology, suggesting that targeting senescence offers therapeutic potential for treating tauopathy associated This study focuses on identifying non-invasive biomarkers validating their responses to well-characterized senolytic therapy combining dasatinib quercetin (D+Q), widely used mouse model, PS19. We employed human-translatable MRI measures, including water extraction with phase-contrast arterial spin tagging (WEPCAST) MRI, T2 relaxation under (TRUST), longitudinally assessed brain physiology high-resolution structural evaluated regional volumes PS19 mice. Our data reveal increased BBB permeability, decreased oxygen fraction, atrophy 9-month-old mice compared littermate controls. (D+Q) treatment effectively preserves integrity, rescues cerebral hypometabolism, attenuates atrophy, alleviates tau hyperphosphorylation Mechanistically, D+Q induces shift microglia from disease-associated homeostatic state, reducing senescence-like microglial phenotype marked p16/INK4a. D+Q-treated exhibit enhanced cue-associated cognitive performance tracing fear conditioning test vehicle-treated littermates, implying improved function treatment. results pave way application as well these noninvasive clinical trials neurological disorders.

Language: Английский

Citations

1
Applying Retinal Vascular Structures Characteristics Coupling with Cortical Visual System in Alzheimer’s Disease Spectrum Patients DOI Creative Commons
Lianlian Wang, Zheqi Hu, Haifeng Chen

et al.

Brain Sciences, Journal Year: 2023, Volume and Issue: 13(2), P. 339 - 339

Published: Feb. 16, 2023

Cortical visual system dysfunction is closely related to the progression of Alzheimer’s Disease (AD), while retinal vascular structures play an important role in integrity function network and are a potential biomarker AD. This study explored association between cortical AD-spectrum patients, it established screening tool detect preclinical AD based on these parameters identified examination. A total 42 subjects were enrolled distributed into two groups: 22 patients with cognitive impairment 20 healthy controls. All participants underwent neuropsychological tests, optical coherence tomography angiography resting-state fMRI imaging. Seed-based functional connectivity analysis was used construct network. The further subjects. found that group displayed prominently decreased mainly involving right inferior temporal gyrus, left supramarginal gyrus postcentral gyrus. Meanwhile, we observed structure characteristics deteriorated decline system. Our provided novel insights aberrant strongly emphasized critical characteristics, which could be as biomarkers for diagnosing monitoring

Language: Английский

Citations

3
Lower cerebral oxygen utilization is associated with Alzheimer’s disease-related neurodegeneration and poorer cognitive performance among apolipoprotein E ε4 carriers DOI
W Hudson Robb, Omair A. Khan,

Humza A. Ahmed

et al.

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2021, Volume and Issue: 42(4), P. 642 - 655

Published: Nov. 7, 2021

Oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO 2 ) are markers homeostasis metabolism that may offer insights into abnormal changes in brain aging. The present study cross-sectionally related OEF CMRO to cognitive performance structural neuroimaging variables among older adults (n = 246, 74 ± 7 years, 37% female) tested whether apolipoprotein E ( APOE)-ε4 status modified these associations. Main effects were null (p-values >0.06), interactions with APOE-ε4 on imaging outcomes >0.06). However, interacted language (p 0.002), executive function 0.03), visuospatial 0.005), episodic memory performances hippocampal 0.006) inferior lateral ventricle volumes 0.02). In stratified analyses, lower worse 0.02) 0.03) carriers only. Associations between primarily driven by existing impairment. Congruence across results as well volume findings suggest interact the pathogenesis Alzheimer’s disease neurodegeneration.

Language: Английский

Citations

6
Magnetic Resonance Imaging in Animal Models of Alzheimer’s Disease Amyloidosis DOI
Ruiqing Ni

Published: Oct. 15, 2021

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

Language: Английский

Citations

4