Small animal magnetic resonance imaging: a means of studying the development of structural pathologies in the rat brain.

Small animal magnetic resonance imaging (SAMRI) was developed to detect structural tissue changes associated with disease states in animal models. The disease state of particular interest here is that associated with long-term alcohol abuse. The small animal model used for this study was the thiamine-deficient Sprague-Dawley rat, a model that provides a relatively rapid means of mimicking the ventriculomegaly frequently found in human chronic alcohol abusers. A custom-designed coil tuned to the magnetic field of a 1.5 Tesla clinical magnetic resonance imager provided the technology necessary to delineate discreet regions of the rat brain with clarity. Adult, male rats were imaged, placed on a thiamine-deficient pellet diet for approximately 6 weeks, and then reimaged. Treatment associated enlargement of the lateral ventricles identified in the images was verified by posttreatment histological analysis of the brains of these rats. The results demonstrated that SAMRI is capable of providing dramatic and reliable visual evidence of pathological structural changes in small tissue volumes with high resolution and reproducibility. Furthermore, the noninvasiveness of SAMRI allowed for imaging of the same animals over time, thereby reducing the numbers of animals needed for convincing documentation of the changes in ventricular size.

Regulation of Na+, K(+)-ATPase by chronic ethanol exposure of PC 12 cells.

The effects of chronic ethanol exposure on Na+, K(+)-ATPase were investigated in PC 12 cells. Inclusion of ethanol in the Na+, K(+)-ATPase assay (i.e. in vitro addition of ethanol) inhibited enzyme activity. Conversely, intrinsic Na+, K(+)-ATPase activity was increased after chronic ethanol exposure of the cells. This increase in Na+, K+ pumps occurred without any alteration in the inhibitory effects of in vitro ethanol. A similar response was observed when the chronic treatments were carried out using serum-free defined medium. The effects of other agents, which like ethanol decrease membrane order, were investigated. The addition of ketamine and tert-butanol in vitro caused a concentration-dependent inhibition of Na+, K(+)-ATPase activity. However, chronic exposure of the PC 12 cells to tert-butanol or ketamine did not alter either intrinsic Na+, K(+)-ATPase activity or the inhibitory effects of ethanol in vitro. Maintenance of PC 12 cells in medium containing ethanol resulted in an increase in the intracellular content of Na+ without any change in the K+ levels. In contrast, maintenance of the cells in medium containing tert-butanol did not alter intracellular levels of Na+ or K+. The present study shows that the ethanol-induced increase in Na+, K+ pumps involved an increase in the intracellular content of Na+. This increase in Na+ content did not appear to be secondary to an inhibition of Na+, K(+)-ATPase activity.

MR imaging of normal rat brain at 0.35 T and correlated histology.

A custom-built small-animal transceiver was used for in vivo imaging of normal rat brain at 0.35 T, with the objective of identifying anatomic components by comparison of images with corresponding histologic sections. The cerebrum, cerebellum, brain stem, ventricles, hippocampus, and subarachnoid space were identified and cerebrospinal fluid (CSF) was differentiated from gray matter and white matter on coronal and transaxial magnetic resonance (MR) images. These images compare favorably with those obtained by others at higher field strengths in regard to delineating major neuroanatomic structures. It is concluded that this technique will be useful for investigating small-animal models of human neurologic disease involving morphologic and morphometric changes in gray matter, white matter, and CSF-filled spaces.

Diuretic and natriuretic effects of sorbinil, an aldose reductase inhibitor.

The renal effects of sorbinil, an aldose reductase inhibitor that interferes with the conversion of glucose to sorbitol, were studied in rats and rabbits before and after fluid deprivation. The intracellular osmolar solute, sorbitol, is found in increasing concentrations from cortex to medulla in the kidney and may be involved in the urinary concentrating mechanism. Oral administration of sorbinil in the rabbit resulted in significant increases in urine flow rate and sodium excretion with a tendency toward decreased urine osmolality and increased potassium excretion both before and after water deprivation. When fluid intake was controlled in the rat study, significant increases in urine flow rate and sodium and potassium excretion and a significant decrease in urine osmolality occurred only in response to fluid deprivation. Thus, sorbinil has diuretic and natriuretic properties and may prevent the normal concentration of urine in the antidiuretic animal.

Magnetic resonance imaging (MRI) and pathophysiology of the rat kidney in streptozotocin-induced diabetes.

Proton magnetic resonance imaging was performed on rats before induction of diabetes with streptozotocin (STZ) and at 2 and 12 days postinduction. Images revealed an increase in maximal longitudinal and axial dimensions of the kidneys at 2 days and a further increase at 12 days. Similarly, an increase in the size of the remaining kidney was seen in a rat which underwent uninephrectomy as a positive control. Two major differences were observed between the kidney undergoing compensatory hypertrophy and those developing diabetic nephropathy: (i) Expansion of the renal vasculature was seen only in images of the diabetic rat; (ii) A loss in conspicuity of the normal corticomedullary junction was seen in the T2-weighted images of the diabetic rat but not in the uninephrectomized rat. Histologic examination revealed that the medulla increased to a size greater than the cortex during diabetic nephropathy whereas the medullary volume was less than that of the cortex during compensatory hypertrophy. In vitro T1 relaxation times in cortex, outer medulla and inner medulla of kidneys from control rats were measured and compared with the same respective regions in diabetic rats. When these values were correlated with tissue water content, a linear increase in relaxation rate versus percent water content from cortex to inner medulla was found in the control kidneys, but this correlation was absent in diabetic nephropathy. These studies demonstrate that MRI is an effective noninvasive tool for studying the course of renal hypertrophy and hydration changes in the development of renal disease in STZ-induced diabetes in the rat.

Magnetic resonance imaging and histopathology of hydronephrosis in the rat.

Magnetic resonance imaging revealed conspicuously hyperintense regions in the papillary area of kidneys of three untreated rats. When the kidneys were examined histologically, a hydronephrosis associated with the presence of bacteria was found. This study relates magnetic resonance images of an early stage of hydronephrosis to its histological picture.

Thiazide diuretics inhibit chloride absorption by rabbit distal colon.

In order to investigate the cellular mechanisms of action of thiazide diuretics, the effect of diuretic and nondiuretic thiazide compounds on Cl- absorption across rabbit distal colon was assessed in tissues mounted in Ussing chambers. This epithelium absorbs Cl- via an active electroneutral transport process. Net 36Cl- absorption across short-circuited tissues was decreased 53, 36 and 20% after addition of 10(-4) M trichlormethiazide, bendroflumethiazide or hydrochlorothiazide, respectively, to the mucosal bathing solution. This inhibitory effect was a result of a decrease in the mucosa-to-serosa unidirectional Cl- flux (P less than .02). Neither the serosa-to-mucosa Cl- flux nor Isc was affected by the thiazides. Thiazide diuretics may exert their effect on Cl- transport across rabbit distal colon through inhibition of a Cl(-)-HCO-3 exchange mechanism. The nondiuretic thiazide, diazoxide, had no effect on Cl- transport. The similarity between the diuretic potency of these compounds and their potency as inhibitors of Cl- absorption by rabbit colon suggests that the thiazides have a similar mechanism of action in renal epithelia.