Propofol reduced rCBF and rCMRO2 comparably. Sevoflurane reduced rCBF less than propofol but rCMRO2 to an extent similar to propofol. These reductions in flow and metabolism were partly attenuated by adjunct N2O. S+N especially reduced the oxygen extraction fraction, suggesting disturbed flow-activity coupling in humans at a moderate depth of anesthesia.

Background-Computed tomography (CT) is increasingly used to detect coronary artery disease, but the evaluation of stenoses is often uncertain. Perfusion imaging has an established role in detecting ischemia and guiding therapy. Hybrid positron emission tomography (PET)/CT allows combination angiography and perfusion imaging in short, quantitative, low-radiation-dose protocols. Methods and Results-We enrolled 107 patients with an intermediate (30% to 70%) pretest likelihood of coronary artery disease. All patients underwent PET/CT (quantitative PET with 15 O-water and CT angiography), and the results were compared with the gold standard, invasive angiography, including measurement of fractional flow reserve when appropriate. Although PET and CT angiography alone both demonstrated 97% negative predictive value, CT angiography alone was suboptimal in assessing the severity of stenosis (positive predictive value, 81%). Perfusion imaging alone could not always separate microvascular disease from epicardial stenoses, but hybrid PET/CT significantly improved this accuracy to 98%. The radiation dose of the combined PET and CT protocols was 9.3 mSv (86 patients) with prospective triggering and 21.8 mSv (21 patients)

Positron emission tomography permits noninvasive measurement of regional glucose uptake in vivo in humans. We employed this technique to determine the effect of FFA on glucose uptake in leg, arm, and heart muscles. Six normal men were studied twice under euglycemic hyperinsulinemic (serum insulin -500 pmol/liter) conditions, once during elevation of serum FFA by infusions of heparin and Intralipid (serum FFA 2.0±0.4 mmol/liter), and once during infusion of saline (serum FFA 0.1±0.01 mmol/liter). Regional glucose uptake rates were measured using positron emission tomography-derived 'Ffluoro-2-deoxy-D-glucose kinetics and the three Elevation of plasma FFA decreased whole body glucose uptake by 31±2% (1,960±130 vs. 2,860±250 Mmol/min, P < 0.01, FFA vs. saline study). This decrease was due to inhibition of glucose uptake in the heart by 30±8% (150±33 vs. 200±28 smol/min, P < 0.02), and in skeletal muscles; both when measured in femoral (1,594±261 vs. 2,272±328 Mmol/ min. 25+13%) and arm muscles (1,617±411 to 2,305±517Mmol/min, P < 0.02, 31±6%). Whole body glucose uptake correlated with glucose uptake in femoral (r = 0.75, P < 0.005), and arm muscles (r = 0.69, P < 0.05) but not with glucose uptake in the heart (r = 0.04, NS). These data demonstrate that the glucose-FFA cycle operates in vivo in both heart and skeletal muscles in humans. (J.

Both anesthetic agents caused a global reduction of rCBF (propofol > sevoflurane) at the 1 MAC/EC(50) level. The effect was maintained at higher propofol concentrations, whereas 2 MAC sevoflurane caused noticeable flow redistribution. Despite the marked global changes, SPM analysis enabled detailed localization of regions with the greatest relative decreases.

gene. In the mutant CA1 region, synaptic and extrasynaptic AMPA receptors on dendrites and spines were severely reduced to 35-37% of control levels, whereas reduction was mild for extrasynaptic receptors on somata (74%) and no significant decrease was seen for intracellular receptors within spines. In the mutant CA3 region, synaptic AMPA receptors were reduced mildly at asymmetrical synapses in the stratum radiatum (67% of control level), and showed no significant decrease at mossy fiber-CA3 synapses. Therefore, γ-8 is abundantly distributed on hippocampal excitatory synapses and extrasynaptic membranes, and plays an important role in increasing the number of synaptic and extrasynaptic AMPA receptors on dendrites and spines, particularly, in the CA1 region.

No abstract

Recent studies on cerebrospinal fluid (CSF) homeostasis emphasize the importance of water flux through the pericapillary (Virchow–Robin) space for both CSF production and reabsorption (Oreskovic and Klarica hypothesis), and challenge the classic CSF circulation theory, which proposes that CSF is primarily produced by the choroid plexus and reabsorbed by the arachnoid villi. Active suppression of aquaporin-1 (AQP-1) expression within brain capillaries and preservation of AQP-1 within the choroid plexus together with pericapillary water regulation by AQP-4 provide a unique opportunity for testing this recent hypothesis. We investigated water flux into three representative regions of the brain, namely, the cortex, basal ganglia, and third ventricle using a newly developed water molecular MRI technique based on JJ vicinal coupling between 17O and adjacent protons and water molecule proton exchanges (JJVCPE imaging) in AQP-1 and AQP-4 knockout mice in vivo. The results clearly indicate that water influx into the CSF is regulated by AQP-4, and not by AQP-1, strongly supporting the Oreskovic and Klarica hypothesis.

Neural circuits are initially redundant but rearranged through activity-dependent synapse elimination during postnatal development. This process is crucial for shaping mature neural circuits and for proper brain function. At birth, Purkinje cells (PCs) in the cerebellum are innervated by multiple climbing fibers (CFs) with similar synaptic strengths. During postnatal development, a single CF is selectively strengthened in each PC through synaptic competition, the strengthened single CF undergoes translocation to a PC dendrite, and massive elimination of redundant CF synapses follows. To investigate the cellular mechanisms of this activity-dependent synaptic refinement, we generated mice with PC-selective deletion of the Ca v 2.1 P/Q-type Ca 2+ channel, the major voltage-dependent Ca 2+ channel in PCs. In the PC-selective Ca v 2.1 knockout mice, Ca 2+ transients induced by spontaneous CF inputs are markedly reduced in PCs in vivo. Not a single but multiple CFs were equally strengthened in each PC from postnatal day 5 (P5) to P8, multiple CFs underwent translocation to PC dendrites, and subsequent synapse elimination until around P12 was severely impaired. Thus, P/Q-type Ca 2+ channels in postsynaptic PCs mediate synaptic competition among multiple CFs and trigger synapse elimination in developing cerebellum.