The combined effects on neuronal activation and blood-brain barrier permeability of time and n-3 polyunsaturated fatty acids in mice, as measured in vivo using MEMRI.

N-3 polyunsaturated fatty acids (n-3 PUFA) are known to have cardiovascular and neuroprotective properties in both humans and rodents. Here, we use manganese-enhanced magnetic resonance imaging (MEMRI) to compare the effects of these polyunsaturated fatty acids on the combined effects of neuronal activity and integrity of blood-brain barrier integrity with saturated fatty acids from buttermilk. C57BL/6 mice (4 weeks old) were fed isocaloric diets containing 3% fish oil (3% FO, n=5), 12% fish oil (FO, n=6), 3% buttermilk (3% BM, n=6) or 12% buttermilk (12% BM, n=6) for 6 months. Following metabolic cage analysis these mice were scanned using a standard MEMRI protocol at 28-32 weeks of age. Adult mice aged 28-32 weeks old (RM3, n=5) and 15-16 weeks old (YRM3, n=4) maintained on standard rodent chow were also studied to assess age-related changes in brain barrier systems and neuronal activity. Signal intensity (SI) in the anterior pituitary (AP), arcuate hypothalamic nucleus (ARC), ventromedial hypothalamic nucleus (VMH) and the paraventricular hypothalamic nucleus (PVN) was significantly reduced in young compared to older mice fed standard chow. Furthermore, fish oil supplementation led to a decrease in SI within the ARC and PVN, reaching significance in the VMH in age-matched controls. Interestingly, both fish oil and buttermilk supplementation resulted in a significant increase in SI within the AP, a structure outside the BBB. We conclude that MEMRI is able to detect the combined effects of the integrity of neuronal activity and blood-brain barrier permeability in the hypothalamus associated with dietary manipulation and aging.

Differential patterns of neuronal activation in the brainstem and hypothalamus following peripheral injection of GLP-1, oxyntomodulin and lithium chloride in mice detected by manganese-enhanced magnetic resonance imaging (MEMRI).

We have used manganese-enhanced magnetic resonance imaging (MEMRI) to show distinct patterns of neuronal activation within the hypothalamus and brainstem of fasted mice in response to peripheral injection of the anorexigenic agents glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM) and lithium chloride. Administration of both GLP-1 and OXM resulted in a significant increase in signal intensity (SI) in the area postrema of fasted mice, reflecting an increase in neuronal activity within the brainstem. In the hypothalamus, GLP-1 administration induced a significant reduction in SI in the paraventricular nucleus and an increase in the ventromedial hypothalamic nucleus whereas OXM reduced SI in the arcuate and supraoptic nuclei of the hypothalamus. These data indicate that whilst these related peptides both induce a similar effect on neuronal activity in the brainstem they generate distinct patterns of activation within the hypothalamus. Furthermore, the hypothalamic pattern of signal intensity generated by GLP-1 closely matches that generated by peripheral injection of LiCl, suggesting the anorexigenic effects of GLP-1 may be in part transmitted via nausea circuits. This work provides a framework by which the temporal effects of appetite modulating agents can be recorded simultaneously within hypothalamic and brainstem feeding centres.

Differential hypothalamic neuronal activation following peripheral injection of GLP-1 and oxyntomodulin in mice detected by manganese-enhanced magnetic resonance imaging.

The anorexigenic gut hormones oxyntomodulin (OXM) and glucagon-like peptide-1 (GLP-1) are thought to physiologically regulate appetite and food intake. Using manganese-enhanced magnetic resonance imaging, we have shown distinct patterns of neuronal activation in the hypothalamus in response to intraperitoneal injections into fasted mice of 900 and 5400 nmol/kg OXM or 900 nmol/kg GLP-1. Administration of OXM at either dose resulted in a reduced rate of signal enhancement, reflecting a reduction in neuronal activity, in the arcuate, paraventricular, and supraoptic nuclei of the hypothalamus. Conversely, GLP-1 caused a reduction in signal enhancement in the paraventricular nucleus only and an increase in the ventromedial hypothalamic nucleus. Our data show that these two apparently similar peptides generate distinct patterns of activation within the hypothalamus, suggesting that GLP-1 and OXM may act via different hypothalamic pathways.

Manganese-enhanced magnetic resonance imaging (MEMRI) without compromise of the blood-brain barrier detects hypothalamic neuronal activity in vivo.

There is growing interest in the use of manganese-enhanced MRI (MEMRI) to detect neuronal activity and architecture in animal models. The MEMRI neuronal activity studies have been generally performed either by stereotactic brain injection or by systemic administration of Mn(2+) in conjunction with the disruption of the blood-brain barrier (BBB). These approaches, however, have limited the use of MEMRI because of the procedure-related morbidity/mortality or because brain activity measured by these methods can diverge from genuine physiological responses. In this study, the hypothesis that MEMRI, performed with systemic administration of Mn(2+) without compromising the BBB integrity, is able to detect hypothalamic function associated with feeding was tested. This procedure was tested on a simple physiological condition, fasting, and with this method temporal and regional differences in Mn(2+) enhancement could be detected. It is concluded that MEMRI can be used to study hypothalamic function in the murine brain without compromising the BBB. It was also shown that region-specific Mn(2+) enhancement in the mouse brain can be modulated by fasting. More importantly, this non-invasive in vivo imaging technique is able to demonstrate differences in brain activities, previously possible only by in vitro studies.

T2 relaxation values in the developing preterm brain.

BACKGROUND AND PURPOSE: MR imaging is increasingly used to assess maturation and disease in the preterm brain. Knowledge of the changes in T2 values with increasing postmenstrual age (PMA) will aid image interpretation and help in the objective assessment of maturation and disease of the brain in infants. The aim of this study was to obtain T2 values in the preterm brain from 25 weeks' gestational age (GA) until term-equivalent age in infants who had normal neurodevelopmental findings at a minimum corrected age of 1 year. METHODS: The study group consisted of 18 preterm infants, born at 33 weeks' GA or sooner. The median GA of the infants at birth was 27 weeks (range, 23-33 weeks), and the median PMA at imaging was 31 weeks (range, 25-41 weeks). T2 measurements were obtained using a 1.0-T MR system and a four-echo pulse sequence (TR/TE, 2500/ 30, 60, 110, and 600). T2 values were measured in the thalami, lentiform nuclei, frontal white matter, occipital white matter, and central white matter at the level of the centrum semiovale. RESULTS: A significant negative linear correlation between T2 values and PMA was demonstrated in the lentiform nuclei (P =.003), frontal white matter (P <.0001), occipital white matter (P <.0001), and central white matter at the level of the centrum semiovale (P <.0001). T2 values were not significantly reduced with increasing PMA in the thalami (P =.06). CONCLUSION: T2 values decrease with increasing PMA in the preterm brain.