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Hyperglycemia (blood glucose concentration >150 mg/dL) is common in extremely low gestational age newborns (ELGANs; birth at <28 week gestation). Hyperglycemia increases the risk of brain injury in the neonatal period. The long-term effects are not well understood. In adult rats, hyperglycemia alters hippocampal energy metabolism. The effects of hyperglycemia on the developing hippocampus were studied in rat pups. In Experiment 1, recurrent hyperglycemia of graded severity (moderate hyperglycemia (moderate-HG), mean blood glucose 214.6 ± 11.6 mg/dL; severe hyperglycemia (severe-HG), 338.9 ± 21.7 mg/dL; control, 137.7 ± 2.6 mg/dL) was induced from postnatal day (P) 3 to P12. On P30, the hippocampal neurochemical profile was determined using in vivo 1 H MR spectroscopy. Dendritic arborization in the hippocampal CA1 region was determined using microtubule-associated protein (MAP)-2 immunohistochemistry. In Experiment 2, continuous hyperglycemia (mean blood glucose 275.3 ± 25.8 mg/dL; control, 142.3 ± 2.6 mg/dL) was induced from P2 to P6 by injecting streptozotocin (STZ) on P2. The mRNA expression of glycogen synthase 1 (Gys1), lactate dehydrogenase (Ldh), glucose transporters 1 (Glut1) and 3 (Glut3) and monocarboxylate transporters 1 (Mct1), 2 (Mct2) and 4 (Mct4) in the hippocampus was determined on P6. In Experiment 1, MRS demonstrated lower lactate concentration and glutamate/glutamine (Glu/Gln) ratio in the severe-HG group, compared with the control group (p < 0.05). Phosphocreatine/creatine ratio was higher in both hyperglycemia groups (p < 0.05). MAP-2 histochemistry demonstrated longer apical segment length, indicating abnormal synaptic efficacy in both hyperglycemia groups (p < 0.05). Experiment 2 showed lower Glut1, Gys1 and Mct4 expression and higher Mct1 expression in the hyperglycemia group, relative to the control group (p < 0.05). These results suggest that hyperglycemia alters substrate transport, lactate homeostasis, dendritogenesis and Glu-Gln cycling in the developing hippocampus. Abnormal neurochemical profile and dendritic structure due to hyperglycemia may partially explain the long-term hippocampus-mediated cognitive deficits in human ELGANs., (Copyright © 2018 John Wiley & Sons, Ltd.)

In this work, we investigated the frequency-offset dependence of the rotating frame longitudinal (R(1ρ)) and transverse (R(2ρ)) relaxation rate constants when using hyperbolic-secant adiabatic full passage pulses or continuous-wave spin-lock irradiation. Phantom and in vivo measurements were performed to validate theoretical predictions of the dominant relaxation mechanisms existing during adiabatic full passage pulses when using different settings of the frequency offset relative to the carrier. In addition, adiabatic R(1ρ) and R(2ρ) values of total creatine and N-acetylaspartate were measured in vivo from the human brain at 4 T. When the continuous-wave pulse power was limited to safe specific absorption rates for humans, simulations revealed a strong dependence of R(1ρ) and R(2ρ) values on the frequency offset for both dipolar interactions and anisochronous exchange mechanisms. By contrast, theoretical and experimental results showed adiabatic R(1ρ) and R(2ρ) values to be practically invariant within the large subregion of the bandwidth of the hyperbolic-secant pulse where complete inversion was achieved. However, adiabatic R(1ρ) and R(2ρ) values of the methyl protons of total creatine (at 3.03 ppm) were almost doubled when compared with those of the methyl protons of N-acetylaspartate (at 2.01 ppm) in spite of the fact that these resonances were in the flat region of the inversion band of the adiabatic full passage pulses. We conclude that differences in adiabatic R(1ρ) and R(2ρ) values of human brain metabolites are not a result of their chemical shifts, but instead reflect differences in dynamics., (Copyright © 2011 John Wiley & Sons, Ltd.)

Ascorbate (vitamin C, Asc) was quantified in vivo using short-TE (1)H NMR spectra from a previously published study on regional and developmental changes in the neurochemical profile of the rat brain (Tkac I, Rao R, Georgieff MK, Gruetter R. Magn Reson Med. 2003; 50: 24-32). Asc concentration was quantified on postnatal days P7-P28 from three regions that are of interest in the study of neurocognitive development, i.e. the hippocampus, striatum and cerebral cortex. The previously measured (1)H NMR spectra were re-analyzed using LCModel with the Asc spectrum included in the basis set. The Asc concentration was consistently quantified from all 110 re-analyzed spectra with an estimated fitting error of 7% (i.e. the average Cramer-Rao lower bound). The sensitivity of Asc quantification was sufficiently high to detect regional and developmental changes in Asc concentration. The concentration of Asc was highest on P7, and decreased with age in all three brain regions (p < 0.001) in agreement with previous in vitro studies. At P10 and older postnatal ages, an inhomogeneous distribution of Asc among brain regions was detected. In addition to facilitating the quantification of this important antioxidant concentration, the inclusion of the Asc spectrum in the LCModel basis set improved the quantification accuracy of other brain metabolite concentrations in the neurochemical profile.

Ascorbate (Asc, vitamin C) was quantified in the human brain noninvasively using two different (1)H NMR spectroscopy methods: short-echo time STEAM and MEGA-PRESS homonuclear editing. Taking advantage of increased sensitivity and chemical shift dispersion at 7 T, Asc was quantified with increased reliability relative to our previous study accomplished at 4 T. Asc concentration quantified from short-echo time spectra measured from the occipital lobe of eight healthy subjects ([Asc] = 1.1 +/- 0.3 micromol/g, mean +/- SD) was in excellent agreement with Asc concentration quantified from the same volume of interest using homonuclear editing ([Asc] = 1.2 +/- 0.2 micromol/g). This agreement indicates that at 7 T, Asc can be reliably quantified in the human brain simultaneously with 15 other metabolites. Additional advantages of the short-echo time approach were: shorter measurement time than homonuclear editing and minimal effect of T(2) relaxation on Asc quantification. High magnetic field was also beneficial for Asc quantification with MEGA-PRESS because increased chemical shift dispersion enabled editing with full efficiency, which resulted in a supra-linear gain in signal-to-noise ratio relative to 4 T., (2009 John Wiley & Sons, Ltd.)