Nitroprusside, a vasodilatory nitric oxide donor, is clinically used during vascular surgery and to lower blood pressure in acute hypertension. This article reports a novel application of blood flow (BF) and blood oxygenation level dependent (BOLD) MRI on an 11.7T scanner to image the rat chorioretinal BF and BOLD changes associated with graded nitroprusside infusion. At low doses (1 or 2 μg/kg/min), nitroprusside increased BF as expected but decreased BOLD signals, showing an intriguing BF-BOLD uncoupling. At high doses (3-5 μg/kg/min), nitroprusside decreased BF and markedly decreased BOLD signals. To our knowledge, this is the first pharmacological MRI application of the retina. This approach has potential to open up new avenues to study the drug-related hemodynamic functions and to evaluate the effects of novel therapeutic interventions on BOLD and BF in the normal and diseased retinas.
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http://dx.doi.org/10.1002/mrm.24112 | DOI Listing |
Neurology
January 2025
Leonard Davis School of Gerontology, University of Southern California, Los Angeles.
Background And Objectives: Cerebrovascular reactivity (CVR) represents the ability of cerebral blood vessels to regulate blood flow in response to vasoactive stimuli and is related to cognition in cerebrovascular and neurodegenerative conditions. However, few studies have examined CVR in the medial temporal lobe, known to be affected early in Alzheimer disease and to influence memory function. We aimed to examine whether medial temporal CVR is associated with memory function in older adults with and without mild cognitive impairment (MCI).
View Article and Find Full Text PDFBackground: Apolipoprotein ε4 allele (APOE4) is the strongest genetic risk factor for late-onset Alzheimer's disease (AD) with females having higher risk than males. Compared with non-carriers, cognitively normal, middle-aged APOE4 carriers have lower cerebral blood flow (CBF) decades before clinical symptoms appear. Early intervention to protect CBF would be critical for APOE4 carriers to mitigate AD progression.
View Article and Find Full Text PDFBackground: Psychotic symptoms may manifest in Alzheimer's disease (AD), especially in advanced disease stages and in patients with higher polygenic risk scores for schizophrenia (SCZ-PRS). Such genetic risk seems also to influence grey matter volume (GMV) alterations in patients with psychosis. Since multiple neurotransmitter systems, namely dopamine (DA) and serotonin (5-HT), have been implicated in psychosis, the aim of this study was to investigate whether a SCZ-PRS may explain variance in the association between GMV and the cerebral distribution of DA and 5-HT.
View Article and Find Full Text PDFBackground: Apolipoprotein ε4 allele (APOE4) is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). Compared with non-carriers, cognitively normal APOE4 individuals have shown brain atrophy and lower cerebral blood flow (CBF) decades before AD pathological and clinical symptoms appear. The goal of the study is to determine if using Sirolimus, an FDA-approved mTOR inhibitor, could restore the brain volumes in structures related to cognitive functions and global CBF (gCBF) for asymptomatic APOE4 carriers compared with non-carriers.
View Article and Find Full Text PDFBackground: Hemodynamic signals are the basis of functional brain imaging techniques, such as fMRI and NIRS, and are often used to infer changes in resting-state functional connectivity (RSFC) in Alzheimer's disease (AD) and other dementias. Increasing evidence suggests that disruption of neuronal circuits has been associated with the AD continuum and may precede changes in Ab and tau biomarkers, neurodegeneration, and cognitive impairment. To better understand the changes in brain RSFC through the AD spectrum, we use hemodynamic signals to detect disease onset, progression, and response to therapy in a mouse model of AD.
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