Learn More
To determine the relationship between cerebral Glc metabolism and glutamatergic neuronal function, we used 13C NMR spectroscopy to measure, simultaneously, the rates of the tricarboxylic acid cycle and Gln synthesis in the rat cortex in vivo. From these measurements, we calculated the rates of oxidative Glc metabolism and glutamate-neurotransmitter cycling(More)
Functional magnetic resonance imaging (fMRI) in animal models provides a platform for more extensive investigation of drug effects and underlying physiological mechanisms than is possible in humans. However, it is usually necessary for the animal to be anesthetized. In this study, we have used a rat model of direct cortical stimulation to investigate the(More)
The aims of this study were twofold: (i) to determine quantitatively the contribution of glutamate/glutamine cycling to total astrocyte/neuron substrate trafficking for the replenishment of neurotransmitter glutamate; and (ii) to determine the relative contributions of anaplerotic flux and glutamate/glutamine cycling to total glutamine synthesis. In this(More)
Dimethyloxalylglycine (DMOG) is an inhibitor of prolyl-4-hydroxylase domain (PHD) enzymes that regulate the stability of hypoxia-inducible factor (HIF). We investigated the effect of DMOG on the outcome after permanent and transient middle cerebral artery occlusion (p/tMCAO) in the rat. Before and after pMCAO, rats were treated with 40 mg/kg, 200 mg/kg(More)
The cerebral tricarboxylic acid (TCA) cycle rate and the rate of glutamine synthesis were measured in rats in vivo under normal physiological and hyperammonemic conditions using 13C NMR spectroscopy. In the hyperammonemic animals, blood ammonia levels were raised from control values of approximately 0.05 mM to approximately 0.35 mM by an intravenous(More)
The cytokine interleukin-1beta (IL-1beta) is implicated in a broad spectrum of CNS pathologies, in which it is thought to exacerbate neuronal loss. Here, the effects of injecting recombinant rat IL-1beta into the striatum of 3-week-old rats were followed noninvasively from 2 to 123 hr using magnetic resonance imaging and spectroscopy. Four hours after(More)
BACKGROUND Activated microglia are a feature of the host response to neurodegeneration in Parkinson's disease (PD) and are thought to contribute to disease progression. Recent evidence suggests that extracellular α-synuclein (eSNCA) may play an important role in the pathogenesis of PD and that this may be mediated by a microglial response. METHODS We(More)
Functional MRI (fMRI) exploits a relationship between neuronal activity, metabolism, and cerebral blood flow to functionally map the brain. We have developed a model of direct cortical stimulation in the rat that can be combined with fMRI and used to compare the hemodynamic responses to direct and indirect cortical stimulation. Unilateral electrical(More)
Multiple sclerosis is a disease of the central nervous system that is associated with leukocyte recruitment and subsequent inflammation, demyelination and axonal loss. Endothelial vascular cell adhesion molecule-1 (VCAM-1) and its ligand, alpha4beta1 integrin, are key mediators of leukocyte recruitment, and selective inhibitors that bind to the alpha4(More)
The pathogenesis of stroke is multifactorial, and inflammation is thought to have a critical function in lesion progression at early time points. Detection of inflammatory processes associated with cerebral ischemia would be greatly beneficial in both designing individual therapeutic strategies and monitoring outcome. We have recently developed a new(More)