2008 |
Cui, Xu |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Asynchrony of Bold Signal Across Brain Regions
Brain; Brain region; CRISP; Cell Communication and Signaling; Cell Signaling; Characteristics; Classification; Computer Retrieval of Information on Scientific Projects Database; Data Set; Dataset; Encephalon; Encephalons; Functional Magnetic Resonance Imaging; Funding; Grant; Institution; Intracellular Communication and Signaling; Investigation; Investigators; Label; Lead; MRI, Functional; Magnetic Resonance Imaging, Functional; Measures; Methods; NIH; National Institutes of Health; National Institutes of Health (U.S.); Nervous; Nervous System, Brain; Pb element; Research; Research Personnel; Research Resources; Researchers; Resources; Signal Transduction; Signal Transduction Systems; Signaling; Source; Systematics; United States National Institutes of Health; Work; biological signal transduction; experiment; experimental research; experimental study; fMRI; heavy metal Pb; heavy metal lead; hemodynamics; neural; relating to nervous system; research study; response
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1 |
2011 |
Cui, Xu |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
A Quantitative Comparison of Nirs and Fmri Across Multiple Cognitive Tasks
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. INTRODUCTION: Near-infrared spectroscopy (NIRS) is an increasingly popular technology for studying brain function. NIRS offers several advantages relative to functional magnetic resonance imaging (fMRI), including the ability to measure concentration changes of both oxygenated and deoxygenated hemoglobin, finer temporal resolution, and ease of administration, as well as disadvantages, most prominently inferior spatial resolution, inability to directly measure signals from deep-brain structures, and decreased signal-to-noise ratio (SNR). In this study, we compared NIRS and fMRI signals to assess spatial and temporal similarities. METHODS: Thirteen healthy adults (mean age 27.9, age range 21-42, 6 males) underwent simultaneous NIRS and fMRI scanning while they completed four experimental paradigms: left finger tapping (tap), go/no-go (nog), judgment of line orientation (jlo), and an N-back working memory task using visuospatial stimuli (vis). We performed detailed comparisons of the signals in both temporal and spatial domains. To read about other projects ongoing at the Lucas Center, please visit http://rsl.stanford.edu/ (Lucas Annual Report and ISMRM 2011 Abstracts)
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1 |
2015 — 2019 |
Cui, Xu |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Abca1 Regulates White Matter Remodeling and Oligodendrogenesis After Stroke @ Henry Ford Health System
? DESCRIPTION (provided by applicant): Stroke is a major cause of white matter (WM) damage which induces long-term disability. There is limited WM- remodeling in the adult brain. Many neuroprotective treatments of stroke have failed in clinical trials because they cannot protect WM. Therefore, there is a compelling need to investigate the mechanism underlying WM- remodeling and oligodendrogenesis of the adult brain and to develop effective long-term stroke therapy. Cellular cholesterol modulates axonal and dendritic outgrowth and is required for myelination. The level of HDL-cholesterol is related to the progression and recovery of stroke patients. ATP-binding cassette transporter A 1 (ABCA1) is a major cholesterol transporter and plays critical roles in regulation of HDL-cholesterol and ApoE synthesis and metabolism in the central nervous system. Brain specific-ABCA1 deficient (ABCA1-B/-B) mice have very low brain HDL-cholesterol/ApoE level, and exhibit neuronal ultrastructure changes and functional deficits. Both HDL-cholesterol and ApoE increase neurite outgrowth in culture conditions. Our preliminary study shows that ABCA1-B/-B mice exhibited increased WM damage and reduced oligodendrogenesis and exacerbated neurological functional deficits after stroke. Primary cultured neurons derived from ABCA1-B/-B mice show decreased neurite outgrowth, which can be attenuated by HDL treatment. ABCA1-B/-B astrocyte-conditioned media also decreased wild type neurite outgrowth after hypoxic ischemia. Therefore, we propose the following three specific aims: Aim1 To investigate whether brain-deficient in ABCA1 exhibits decreases in WM-remodeling and axonal growth after stroke. ABCA1 -B/-B and floxed-control mice will be subjected to stroke, WM-changes and oligodendrogenesis will be measured. Aim2 To investigate molecular mechanism underlying ABCA1 in regulation of WM-remodeling and oligodendrogenesis after stroke, we will examine whether ABCA1 regulates brain HDL and ApoE level, and whether brain HDL and ApoE levels mediate ABCA1-induced WM-remodeling and oligodendrogenesis after stroke. Aim3 To investigate cellular mechanisms of ABCA1 in regulation of WM-remodeling and oligodendrogenesis, we will examine neurons and oligodendrocytes and the cross talk of astrocytes with neurons and oligodendrocytes on ABCA1-induced WM- remodeling and oligodendrogenesis in vitro and in vivo. We expect that ABCA1 deficient brain will exhibit significant decreases in HDL and ApoE level, and decreases WM-remodeling and oligodendrogenesis as well as reduced functional outcome after stroke. The level of HDL/ApoE in brain or cerebrospinal fluid will, at least partially, mediate ABCA1-induced WM-remodeling and oligodendrogenesis in the ischemic brain after stroke. To our knowledge, no one has investigated the functional effect of ABCA1 on oligodendrogenesis and WM- remodeling post-stroke recovery, especially by using ABCA1-B/-B mice. The new insights gleaned from this study will contribute to our understanding of the beneficial role of ABCA1/HDL-C/ApoE in brain plasticity which will impact development of rational restorative approaches to improve neurological outcome for stroke patients.
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0.913 |
2020 — 2021 |
Cui, Xu Jiang, Quan [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Investigation of D-4f Effects of Neurovascular Remodeling After Diabetic Stroke @ Henry Ford Health System
ABSTRACT Ischemic stroke patients with Diabetes mellitus (DM) exhibit a distinct risk-factor and etiologic profile and a worse neurovascular prognosis than non-DM patients. Therefore, there is a compelling need to investigate neurovascular changes after stroke in the DM and non-DM population and to develop therapeutic approaches specifically designed to reduce neurological deficits after stroke. Type 2 diabetes (T2DM) constitutes 90% of diabetic patients and is associated with low high-density lipoprotein cholesterol (HDL-C), impairment of the anti-oxidative capacity of HDL-C, low phosphorylation of endothelial nitric oxide synthase (p-eNOS), and with reduced ATP-binding cassette transporter A1 (ABCA1) gene expression. D-4F is an economical apolipoprotein A-I (ApoA-I) mimetic peptide, presently employed in clinical trials to reduce coronary atherosclerosis in patients with acute coronary syndrome. However, the therapeutic effects of D-4F in post-ischemic stroke have not been investigated. Our preliminary data show that D-4F treatment of stroke starting 2h or 24h after ischemic stroke improves recovery of neurological function in both T2DM and non-DM mice and also increases p-eNOS and ABCA1 in the ischemic brain. In a novel and clinically relevant approach, based on our robust preliminary data, we propose to use D-4F in the treatment of stroke in the non-DM and T2DM population in mice. We seek to develop D-4F as a novel neurorestorative therapy to reduce white matter (WM) dysfunction and vascular damage, in T2DM and non-DM mice when treatment is initiated at 24h after onset of ischemic stroke. In addition, most development of stroke treatments has focused on young adult animals, but not on old animals, the prevalent population with stroke. Increased age also increases neurological impairment after stroke. We have also developed and implemented multimodality MRI imaging which can dynamically monitor neurovascular remodeling in both the animal and the patient. In the current study, we will measure WM and vascular changes and elucidate the mechanisms of action of D-4F in young adult and aged animals with and without T2DM after stroke. Our hypothesis is that D-4F increases ABCA1 and p-eNOS signaling activity which mediates vascular and WM remodeling and in concert improve functional outcome after stroke. We, therefore, propose two highly integrated and longitudinally designed Specific Aims. Aim 1 will investigate the delayed (24h after stroke) therapeutic effects of D-4F in non-DM and T2DM in young adult and aged mice after stroke. The differences in cerebral WM and vascular changes, and neurological functional outcome after stroke between non-DM and T2DM mice treated with or without D-4F will be analyzed. MRI will be employed to measure the dynamics of neurovascular reorganization underlying therapeutic response and recovery. In Aim 2, using eNOS knockout mice and specific loss of brain ABCA1 mice, we will investigate the mechanisms by which D-4F promotes neurovascular remodeling and hence, neurological recovery. The long-term objective of this RO1 is to develop a neurorestorative treatment for stroke in patients with or without diabetes.
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0.913 |