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The aim of this study was to investigate the various MRI biophysical models in the measurements of local cerebral metabolic rate of oxygen (CMRO(2)) and the corresponding relationship with cerebral blood flow (CBF) during brain activation. This aim was addressed by simultaneously measuring the relative changes in CBF, cerebral blood volume (CBV), and blood(More)
The discovery that rapamycin increases lifespan in mice and restores/delays many aging phenotypes has led to the speculation that rapamycin has 'anti-aging' properties. The major question discussed in this review is whether a manipulation that has anti-aging properties can alter the onset and/or progression of Alzheimer's disease, a disease in which age is(More)
The purpose of this study was to investigate activation-induced hypermetabolism and hyperemia by using a multifrequency (4, 8, and 16 Hz) reversing-checkerboard visual stimulation paradigm. Specifically, we sought to (i) quantify the relative contributions of the oxidative and nonoxidative metabolic pathways in meeting the increased energy demands [i.e.,(More)
The aim of this study was to investigate the relationship between relative cerebral blood flow (delta CBF) and relative cerebral metabolic rate of oxygen (delta CMRO(2)) during continuous visual stimulation (21 min at 8 Hz) with fMRI biophysical models by simultaneously measuring of BOLD, CBF and CBV fMRI signals. The delta CMRO(2) was determined by both a(More)
Risk factors and cognitive sequelae of brain arteriolosclerosis pathology are not fully understood. To address this, we used multimodal data from the National Alzheimer's Coordinating Center and Alzheimer's Disease Neuroimaging Initiative data sets. Previous studies showed evidence of distinct neurodegenerative disease outcomes and clinical-pathological(More)
By restoring mitochondrial function, methylene blue (MB) is an effective neuroprotectant in many neurological disorders (e.g., Parkinson's and Alzheimer's diseases). MB has also been proposed as a brain metabolic enhancer because of its action on mitochondrial cytochrome c oxidase. We used in vitro and in vivo approaches to determine how MB affects brain(More)
Medulloblastoma is an aggressive childhood cerebellar tumor. We recently reported a mouse model with conditional deletion of Patched1 gene that recapitulates many characteristics of the human medulloblastoma. Qualitative symptoms observed in the mouse model include irregular stride length, impaired cranial nerve function and decreased motor coordination and(More)
Vascular pathology is a major feature of Alzheimer's disease (AD) and other dementias. We recently showed that chronic administration of the target-of-rapamycin (TOR) inhibitor rapamycin, which extends lifespan and delays aging, halts the progression of AD-like disease in transgenic human (h)APP mice modeling AD when administered before disease onset. Here(More)
Mutations in SURF1 (surfeit locus protein 1) COX (cytochrome c oxidase) assembly protein are associated with Leigh's syndrome, a human mitochondrial disorder that manifests as severe mitochondrial phenotypes and early lethality. In contrast, mice lacking the SURF1 protein (Surf1-/-) are viable and were previously shown to have enhanced longevity and a(More)
Alzheimer's disease (AD) is characterized by age-dependent biochemical, metabolic, and physiologic changes. These age-dependent changes ultimately converge to impair cognitive functions. This study was carried out to examine the metabolic changes by probing glucose and tricarboxylic acid cycle metabolism in a 7-month-old triple transgenic mouse model of AD(More)