NMR detection of graphene nanoribbons

Nobel prize winning material as "the thinnest material in our universe", graphene, a single atom thick sheet of sp2 carbon atoms, promises a diverse range of applications from composite materials to quantum dots, and even in several bioengineering applications. For graphene, that availability is encumbered by having to surmount the high cohesive van der Waals energy (5.9 kJ mol-1 carbon) adhering graphitic sheets to one another. Moreover, graphene being extremely hydrophobic, it has low solubility in water. Here we demonstrate the feasibility of developing biological graphene dispersions using wet chemistry and ultra sonication. 13C NMR spectra of graphene dispersions indicate the presence of graphene carbon signature in solution. Our future work is to use this graphene dispersion in a cellular assay to explore graphene-protein binding and also to study the graphene nanoribbon structures as contrast agents and drug delivery

Kaempferol Treatment after Traumatic Brain Injury during Early Development Mitigates Brain Parenchymal Microstructure and Neural Functional Connectivity Deterioration at Adolescence.

Targeting mitochondrial ion homeostasis using Kaempferol, a mitochondrial Ca2+ uniporter channel activator, improves energy metabolism and behavior soon after a traumatic brain injury (TBI) in developing rats. Because of broad TBI pathophysiology and brain mitochondrial heterogeneity, Kaempferol-mediated early-stage behavioral and brain metabolic benefits may accrue from diverse sources within the brain. We hypothesized that Kaempferol influences TBI outcome by differentially impacting the neural, vascular, and synaptic/axonal compartments. After TBI at early development (P31), functional magnetic resonance imaging and diffusion tensor imaging (DTI) were applied to determine imaging outcomes at adolescence (2 months post-injury). Vehicle and Kaempferol treatments were made at 1, 24, and 48 h post-TBI, and their effects were assessed at adolescence. A significant increase in neural connectivity was observed after Kaempferol treatment as assessed by the spatial extent and strength of the somatosensory cortical and hippocampal resting-state functional connectivity (RSFC) networks. However, no significant RSFC changes were observed in the thalamus. DTI measures of fractional anisotropy (FA) and apparent diffusion coefficient, representing synaptic/axonal and microstructural integrity, showed significant improvements after Kaempferol treatment, with highest changes in the frontal and parietal cortices and hippocampus. Kaempferol treatment also increased corpus callosal FA, indicating measurable improvement in the interhemispheric structural connectivity. TBI prognosis was significantly altered at adolescence by early Kaempferol treatment, with improved neural connectivity, neurovascular coupling, and parenchymal microstructure in select brain regions. However, Kaempferol failed to improve vasomotive function across the whole brain, as measured by cerebrovascular reactivity. The differential effects of Kaempferol treatment on various brain functional compartments support diverse cellular-level mitochondrial functional outcomes in vivo

Brain Energy

Abstract Following the pragmatic practices of anesthesiologists, a person is defined to be in the state of consciousness by the ability to respond to stimuli. C Magnetic Resonance Spectroscopy (MRS), Positron Emission Tomography (PET), and electrophysiology experiments have been directed towards these goals. These studies have measured brain energy production in the form of glucose oxidation in the resting baseline and anesthetized states and have followed regional changes during stimulation from these states. PET and MRS methods have measured the total or baseline energies while neuroimaging studies, by fMRI and PET, have determined the incremental energies during cognitive or sensory stimulations. The most striking result is that the energy consumption supporting neuronal firing in the conscious-awake, baseline state is one to two orders of magnitude larger than the energy changes during stimulation Early functional imaging studies by It soon became clear, however, that the brain did not follow the simple assumptions of "pure insertion" which expects the incremental brain neuronal response to a mental process to be independent of its context. The dependence of brain responses upon their context created problems for cognitive psychology, which had assumed, for example, that all acts of remembering would require brain to use a similar module of "memory". Jerry Fodor, a founder of the field, concluded in 2000 that this original formulation was not supported experimentally and in his book with that title recognized that "the mind does not work that way" In the face of these results, prominent neuroimagers tried to retain the potential value of cognitive concepts by considering that the dependence upon context arose from the non-linear nature of brain responses In this report we examine what neuroimaging can tell us about a human in the state of consciousness by using an alternate approach which does not assume that consciousness is supported by hypothesized mental processes. In our study, brain experiments are used to determine neuronal and energetic properties of a behavioral state, as distinguished from the claims that imaging results localize theorized mental processes in the brain. Furthermore, we include a central role for the high baseline level of neuronal activity that is removed by differencing in the large majority of functional imaging studies. In both these respects they offer a previously untried methodology for relating brain activities to observable behavior. We believe that baseline brain activities provide necessary support for behavioral processes that are characteristic of the human or rodent in the state of consciousness. In our view, memory, intent, etcetera are contingent assumptions of mental processes presumed to underlie actions performed by the person. Rather than hypothesizing and then localizing psychological assumptions about the contents of consciousness, in our studies the subjects, rat or human, are defined as being in a conscious state by observations of reproducible behavior. In our definition, the state of consciousness enables a person to perform the many actions that Zeman ( 2002) called the Psyche, Vol 15, No 2 (2009) Brain Energy 62 contents of consciousness. These are the actions, feelings, thoughts, sensory interconnections, etcetera, which are described in common parlance as being caused by mental processes. These observables are postulated in neuroimaging studies to be identified with concepts, for example, memory, attention or recognition, and are then sought in localized brain activities. Uncertainties in this methodology have been revealed by the widely recognized dependence of these concepts upon the context in which they are embedded. To avoid these complexities we are correlating brain activities not with such specific assumptions about the contents of consciousness, but rather with the state of consciousness of a human or of the rat. We describe the state of consciousness simply by the subject's ability to respond to stimuli using the criteria established in anesthesia We propose that high cerebral energy (and by inference its coupled neuronal activity) in the awake state defines a necessary property of the consciousness state; when the energy is reduced sufficiently, there is loss of consciousness. Two additional brain properties that we have measured are the fMRI activation patterns and neuronal population activity with change with baseline state. In this paper, we first review the methods developed (primarily in our laboratory) to measure brain energy consumption and their use in studies of the coupled neuronal signaling, which is the work of the brain (Section I). These studies have shown that, above a relatively small level of non-functional energy, brain energy consumption is coupled to the firing of glutamatergic neurons in the cerebral cortex and the coupled ATP consumption during neuronal signaling (e.g., action and field potentials, neurotransmitter release, and recycling, etc). Then we describe experimental measurements of brain properties of the state of consciousness (Section II). The brain energy distribution and the range of energy consumption in the fully awake state measured by PET and fMRI studies are reviewed. Overall, it is shown that in the state of consciousness, the brain energy, and by inference the neuronal signaling, is evenly distributed throughout the cortex. Fluctuations in energy are small compared to the resting brain energy in the fully awake state. PET reports of subjects undergoing graded anesthesia are then reviewed to show the reduced energy levels (and its regional distribution) at which subjects lose consciousness, as defined by the loss of response to stimuli. Next we discuss two additional brain properties, fMRI activation patterns and the firing rates of neuronal populations that change significantly with baseline energy. Finally, we discuss implications of our proposal that measurable brain properties provide insight to the state of consciousness (Section III). Current definitions, philosophies, and theories for the state of consciousness are discussed to demonstrate how measurable brain properties are beginning to sketch a physical understanding of the interconnected behavior representing that state, without a priori assumptions about underlying mental processes

White matter abnormalities in the Hdc knockout mouse, a model of tic and OCD pathophysiology

INTRODUCTION: An inactivating mutation in the MATERIALS AND METHODS: We performed exploratory RNA-seq to identify pathological alterations in several brain regions in RESULTS: Exploratory RNA-Seq analysis revealed, unexpectedly, that genes associated with oligodendrocytes and with myelin production are upregulated in the dorsal striatum of these mice. This was confirmed by qPCR, immunostaining, and immunoblotting. These results suggest an abnormality in myelination in the striatum. To test this in an intact mouse brain, we performed whole-brain DISCUSSION: While the DTI literature in individuals with TS is sparse, these results are consistent with findings of disrupted descending cortical projections in patients with tics. Th

Mapping Extracellular pH of Gliomas in Presence of Superparamagnetic Nanoparticles: Towards Imaging the Distribution of Drug-Containing Nanoparticles and Their Curative Effect on the Tumor Microenvironment

Since brain’s microvasculature is compromised in gliomas, intravenous injection of tumor-targeting nanoparticles containing drugs (D-NPs) and superparamagnetic iron oxide (SPIO-NPs) can deliver high payloads of drugs while allowing MRI to track drug distribution. However, therapeutic effect of D-NPs remains poorly investigated because superparamagnetic fields generated by SPIO-NPs perturb conventional MRI readouts. Because extracellular pH (pHe) is a tumor hallmark, mapping pHe is critical. Brain pHe is measured by biosensor imaging of redundant deviation in shifts (BIRDS) with lanthanide agents, by detecting paramagnetically shifted resonances of nonexchangeable protons on the agent. To test the hypothesis that BIRDS-based pHe readout remains uncompromised by presence of SPIO-NPs, we mapped pHe in glioma-bearing rats before and after SPIO-NPs infusion. While SPIO-NPs accumulation in the tumor enhanced MRI contrast, the pHe inside and outside the MRI-defined tumor boundary remained unchanged after SPIO-NPs infusion, regardless of the tumor type (9L versus RG2) or agent injection method (renal ligation versus coinfusion with probenecid). These results demonstrate that we can simultaneously and noninvasively image the specific location and the healing efficacy of D-NPs, where MRI contrast from SPIO-NPs can track their distribution and BIRDS-based pHe can map their therapeutic impact

Neuroimaging Biomarkers of mTOR Inhibition on Vascular and Metabolic Functions in Aging Brain and Alzheimer’s Disease

The mechanistic target of rapamycin (mTOR) is a nutrient sensor of eukaryotic cells. Inhibition of mechanistic mTOR signaling can increase life and health span in various species via interventions that include rapamycin and caloric restriction (CR). In the central nervous system, mTOR inhibition demonstrates neuroprotective patterns in aging and Alzheimer’s disease (AD) by preserving mitochondrial function and reducing amyloid beta retention. However, the effects of mTOR inhibition for in vivo brain physiology remain largely unknown. Here, we review recent findings of in vivo metabolic and vascular measures using non-invasive, multimodal neuroimaging methods in rodent models for brain aging and AD. Specifically, we focus on pharmacological treatment (e.g., rapamycin) for restoring brain functions in animals modeling human AD; nutritional interventions (e.g., CR and ketogenic diet) for enhancing brain vascular and metabolic functions in rodents at young age (5–6 months of age) and preserving those functions in aging (18–20 months of age). Various magnetic resonance (MR) methods [i.e., imaging (MRI), angiography (MRA), and spectroscopy (MRS)], confocal microscopic imaging, and positron emission tomography (PET) provided in vivo metabolic and vascular measures. We also discuss the translational potential of mTOR interventions. Since PET and various MR neuroimaging methods, as well as the different interventions (e.g., rapamycin, CR, and ketogenic diet) are also available for humans, these findings may have tremendous implications in future clinical trials of neurological disorders in aging populations

Preimplantation factor modulates oligodendrocytes by H19-induced demethylation of NCOR2.

Failed or altered gliogenesis is a major characteristic of diffuse white matter injury in survivors of premature birth. The developmentally regulated long noncoding RNA (lncRNA) H19 inhibits S-adenosylhomocysteine hydrolase (SAHH) and contributes to methylation of diverse cellular components, such as DNA, RNA, proteins, lipids, and neurotransmitters. We showed that the pregnancy-derived synthetic PreImplantation Factor (sPIF) induces expression of the nuclear receptor corepressor 2 (NCOR2) via H19/SAHH-mediated DNA demethylation. In turn, NCOR2 affects oligodendrocyte differentiation markers. Accordingly, after hypoxic-ischemic brain injury in rodents, myelin protection and oligodendrocytes' fate are in part modulated by sPIF and H19. Our results revealed an unexpected mechanism of the H19/SAHH axis underlying myelin preservation during brain recovery and its use in treating neurodegenerative diseases can be envisioned

Trajectories of Brain Lactate and Re-visited Oxygen-Glucose Index Calculations Do Not Support Elevated Non-oxidative Metabolism of Glucose Across Childhood

Brain growth across childhood is a dynamic process associated with specific energy requirements. A disproportionately higher rate of glucose utilization (CMRglucose) compared with oxygen consumption (CMRO2) was documented in children's brain and suggestive of non-oxidative metabolism of glucose. Several candidate metabolic pathways may explain the CMRglucose-CMRO2 mismatch, and lactate production is considered a major contender. The ~33% excess CMRglucose equals 0.18 μmol glucose/g/min and predicts lactate release of 0.36 μmol/g/min. To validate such scenario, we measured the brain lactate concentration ([Lac]) in 65 children to determine if indeed lactate accumulates and is high enough to (1) account for the glucose consumed in excess of oxygen and (2) support a high rate of lactate efflux from the young brain. Across childhood, brain [Lac] was lower than predicted, and below the range for adult brain. In addition, we re-calculated the CMRglucose-CMRO2 mismatch itself by using updated lumped constant values. The calculated cerebral metabolic rate of lactate indicated a net influx of 0.04 μmol/g/min, or in terms of CMRglucose, of 0.02 μmol glucose/g/min. Accumulation of [Lac] and calculated efflux of lactate from brain are not consistent with the increase in non-oxidative metabolism of glucose. In addition, the value for the lumped constant for [18F]fluorodeoxyglucose has a high impact on calculated CMRglucose and use of updated values alters or eliminates the CMRglucose-CMRO2 mismatch in developing brain. We conclude that the presently-accepted notion of non-oxidative metabolism of glucose during childhood must be revisited and deserves further investigations