Cerebral water accumulation was studied during induction of brain edema in dystrophin-null transgenic mice (mdx-␤geo) and control mice. Immunofluorescence and immunoelectron microscopic analyses of dystrophin-null brains revealed a dramatic reduction of AQP4 (aquaporin-4) in astroglial end-feet surrounding capillaries (blood-brain barrier) and at the glia limitans (cerebrospinal fluidbrain interface). The AQP4 protein is mislocalized, because immunoblotting showed that the total AQP4 protein abundance was unaltered. Brain edema was induced by i.p. injection of distilled water and 8-deamino-arginine vasopressin. Changes in cerebral water compartments were assessed by diffusion-weighted MRI with determination of the apparent diffusion coefficient (ADC). In dystrophin-null mice and control mice, ADC gradually decreased by 5-6% from baseline levels during the first 35 min, indicating the initial phase of intracellular water accumulation is similar in the two groups. At this point, the control mice sustained an abrupt, rapid decline in ADC to 58% ؎ 2.2% of the baseline at 52.5 min, and all of the animals were dead by 56 min. After a consistent delay, the dystrophin-null mice sustained a similar decline in ADC to 55% ؎ 3.4% at 66.5 min, when all of the mice were dead. These results demonstrate that dystrophin is necessary for polarized distribution of AQP4 protein in brain where facilitated movements of water occur across the blood-brain barrier and cerebrospinal fluid-brain interface. Moreover, these results predict that interference with the subcellular localization of AQP4 may have therapeutic potential for delaying the onset of impending brain edema. Brain edema is associated with many intracranial neuropathological states, such as head trauma, ischemic brain injury, neoplasms, and metabolic diseases including systemic hyponatremia. Although much investigation has addressed the underlying molecular mechanisms and pathophysiology of brain edema, little is known about the regulation of water transport across the blood-brain barrier, the cerebrospinal fluid (CSF)-brain interface, and between extracellular and intracellular compartments in brain parenchyma.It is well recognized that the aquaporin family of water channel proteins is the major pathway by which water rapidly crosses cell membranes (1). Manley et al. recently reported that AQP4 (aquaporin-4; ref. 18) negatively influences the outcome from brain edema (2), and other recent studies also have suggested that AQP4 contributes to the development of brain edema (3, 4). These observations are consistent with the distribution of AQP4 in brain, because the protein is expressed abundantly in a highly polarized distribution in ependymal cells and astroglial membranes facing capillaries and forming the glia limitans (5).Decreased expression of AQP4 protein without changes in the AQP4 mRNA levels was reported recently in brains of Dmd mdx mice (C57BL10 ScSn mdx), a strain carrying a spontaneous mutation that prevents expression of the longest isoform of dystrophin (6)....

BOLD MRI provides noninvasive estimates of regional renal oxygen content and our study demonstrates that this technique may provide a useful tool in UUO which is associated with altered renal oxygen consumption.

Hyperpolarized (13) C-MRI shows promise in the diagnosis and monitoring of early renal changes associated with diabetes, with the pyruvate/lactate ratio as an imaging biomarker for regional renal changes.

Short-term liraglutide treatment did not affect renal haemodynamics but decreased the proximal tubular sodium reabsorption. Blood pressure increased with short-term as opposed to long-term treatment. Catecholamine levels were unchanged and the results did not support a GLP-1-ANP axis. ANG II levels decreased, which may contribute to renal protection by GLP-1 receptor agonists.