Acute hypoxia increases the cerebral metabolic rate:a magnetic resonance imaging study

The aim of the present study was to examine changes in cerebral metabolism by magnetic resonance imaging of healthy subjects during inhalation of 10% O(2) hypoxic air. Hypoxic exposure elevates cerebral perfusion, but its effect on energy metabolism has been less investigated. Magnetic resonance imaging techniques were used to measure global cerebral blood flow and the venous oxygen saturation in the sagittal sinus. Global cerebral metabolic rate of oxygen was quantified from cerebral blood flow and arteriovenous oxygen saturation difference. Concentrations of lactate, glutamate, N-acetylaspartate, creatine and phosphocreatine were measured in the visual cortex by magnetic resonance spectroscopy. Twenty-three young healthy males were scanned for 60 min during normoxia, followed by 40 min of breathing hypoxic air. Inhalation of hypoxic air resulted in an increase in cerebral blood flow of 15.5% (p = 0.058), and an increase in cerebral metabolic rate of oxygen of 8.5% (p = 0.035). Cerebral lactate concentration increased by 180.3% ([Formula: see text]), glutamate increased by 4.7% ([Formula: see text]) and creatine and phosphocreatine decreased by 15.2% (p [Formula: see text]). The N-acetylaspartate concentration was unchanged (p = 0.36). In conclusion, acute hypoxia in healthy subjects increased perfusion and metabolic rate, which could represent an increase in neuronal activity. We conclude that marked changes in brain homeostasis occur in the healthy human brain during exposure to acute hypoxia

Comparison of Global Cerebral Blood Flow Measured by Phase-Contrast Mapping MRI with O-15-H2O Positron Emission Tomography

PURPOSE: To compare mean global cerebral blood flow (CBF) measured by phase‐contrast mapping magnetic resonance imaging (PCM MRI) and by (15)O‐H(2)O positron emission tomography (PET) in healthy subjects. PCM MRI is increasingly being used to measure mean global CBF, but has not been validated in vivo against an accepted reference technique. MATERIALS AND METHODS: Same‐day measurements of CBF by (15)O‐H(2)O PET and subsequently by PCM MRI were performed on 22 healthy young male volunteers. Global CBF by PET was determined by applying a one‐tissue compartment model with measurement of the arterial input function. Flow was measured in the internal carotid and vertebral arteries by a noncardiac triggered PCM MRI sequence at 3T. The measured flow was normalized to total brain weight determined from a volume‐segmented 3D T (1)‐weighted anatomical MR‐scan. RESULTS: Mean CBF was 34.9 ± 3.4 mL/100 g/min measured by (15)O‐H(2)O PET and 57.0 ± 6.8 mL/100 g/min measured by PCM MRI. The measurements were highly correlated (P = 0.0008, R(2) = 0.44), although values obtained by PCM MRI were higher compared to (15)O‐H(2)O PET (absolute and relative differences were 22.0 ± 5.2 mL/100 g/min and 63.4 ± 14.8%, respectively). CONCLUSION: This study confirms the use of PCM MRI for quantification of global CBF, but also that PCM MRI systematically yields higher values relative to (15)O‐H(2)O PET, probably related to methodological bias. Level of Evidence: 3 J. Magn. Reson. Imaging 2017;45:692–699

Genetic Modifiers of Non-Penetrance and RNA Expression Levels in PRPF31-Associated Retinitis Pigmentosa in a Danish Cohort

(1) Background/aims: To examine potential genetic modifiers of disease penetrance in PRPF31-associated retinitis pigmentosa 11 (RP11). (2) Methods: Blood samples from individuals (n = 37) with PRPF31 variants believed to be disease-causing were used for molecular genetic testing and, in some cases (n = 23), also for mRNA expression analyses. Medical charts were used to establish if individuals were symptomatic (RP) or asymptomatic non-penetrant carriers (NPC). RNA expression levels of PRPF31 and CNOT3 were measured on peripheral whole blood using quantitative real-time PCR normalized to GAPDH. Copy number variation of minisatellite repeat element 1 (MSR1) was performed with DNA fragment analysis. (3) Results: mRNA expression analyses on 22 individuals (17 with RP and 5 non-penetrant carriers) revealed no statistically significant differences in PRPF31 or CNOT3 mRNA expression levels between individuals with RP and non-penetrant carriers. Among 37 individuals, we found that all three carriers of a 4-copy MSR1 sequence on their wild-type (WT) allele were non-penetrant carriers. However, copy number variation of MSR1 is not the sole determinant factor of non-penetrance, as not all non-penetrant carriers carried a 4-copy WT allele. A 4-copy MSR1 mutant allele was not associated with non-penetrance. (4) Conclusions: In this Danish cohort, a 4-copy MSR1 WT allele was associated with non-penetrance of retinitis pigmentosa caused by PRPF31 variants. The level of PRPF31 mRNA expression in peripheral whole blood was not a useful indicator of disease status

Recombinant Erythropoietin in Humans Has a Prolonged Effect on Circulating Erythropoietin Isoform Distribution

<div><p>The membrane-assisted isoform immunoassay (MAIIA) quantitates erythropoietin (EPO) isoforms as percentages of migrated isoforms (PMI). We evaluated the effect of recombinant human EPO (rhEPO) on the distribution of EPO isoforms in plasma in a randomized, placebo-controlled, double-blinded, cross-over study. 16 healthy subjects received either low-dose Epoetin beta (5000 IU on days 1, 3, 5, 7, 9, 11 and 13); high-dose Epoetin beta (30.000 IU on days 1, 2 and 3 and placebo on days 5, 7, 9, 11 and 13); or placebo on all days. PMI on days 4, 11 and 25 was determined by interaction of N-acetyl glucosamine with the glycosylation dependent desorption of EPO isoforms. At day 25, plasma-EPO in both rhEPO groups had returned to values not different from the placebo group. PMI with placebo, reflecting the endogenous EPO isoforms, averaged 82.5 (10.3) % (mean (SD)). High-dose Epoetin beta decreased PMI on days 4 and 11 to 31.0 (4.2)% (p<0.00001) and 45.2 (7.3)% (p<0.00001). Low-dose Epoetin beta decreased PMI on days 4 and 11 to 46.0 (12.8)% (p<0.00001) and 46.1 (10.4)% (p<0.00001). In both rhEPO groups, PMI on day 25 was still decreased (high-dose Epoetin beta: 72.9 (19.4)% (p = 0.029); low-dose Epoetin beta: 73.1 (17.8)% (p = 0.039)). In conclusion, Epoetin beta leaves a footprint in the plasma-EPO isoform pattern. MAIIA can detect changes in EPO isoform distribution up til at least three weeks after administration of Epoetin beta even though the total EPO concentration has returned to normal.</p></div