Incidence of hydronephrosis among several production colonies of outbred Sprague-Dawley rats

The incidence of hydronephrosis was determined in nine production colonies of Crl:CD (SD) BR rats (CD rats). Kidneys from 3909 rats were examined and 79 (2.0%) had unilateral or bilateral hydronephrosis. A colony with a relatively high incidence of hydronephrosis (4.1%) was chosen for further study. In unselected rats from this colony the incidence in females (87/1882, 4.6%) was not significantly different from that in males (79/1862, 4.2%). In the same group of rats, hydronephrosis was observed most frequently in the right kidney only (2.3%), followed by bilateral involvement (1.2%) and the left kidney only (0.8%). By selection and inbreeding, the incidence of hydronephrosis was increased dramatically (to 33.6%) in two generations. Hydronephrosis in the CD rat appears to be a highly heritable trait, most likely involving more than one gene.     

An ultrastructural study of the renal medulla in experimental acute pyelonephritis.

Experimental acute pyelonephritis was produced in rats by a combination of intravenous administration of Escherichia coli, strain IMRU-54, and temporary unilateral mechanical ureteral obstruction. Structural alterations of the renal medulla were studied by light and electron microscopy. Major cellular alterations occurred in the vasa recta. Tubular and interstitial cells demonstrated minimal alterations after the brief period of acute inflammation. Polymorphonuclear leukocytes within tubular lumina contained structures resembling E. coli in nonprotoplasts-like form. Numerous protoplast-like organisms, to the exclusion of any other structural forms, were detected within the interstitium of the inner medulla. Nonprotoplast-like structures resembling E. coli were rarely observed in interstitium of the inner medulla. Following relief of ureteral obstruction, clearance of acute inflammation was rapid. In conclusion, hemoatogenous acute pyelonephritis induced by E. coli, IMRU-54, is able to inflict cytological and ultrastructural damage to structural elements of the inner and outer medulla of rats. Vasa recta incurred prominent alterations in endothelia and basement membranes, whereas tubular epithelia and interstitial cells had relatively good structural preservation. The data suggest that intravenously administered E. coli is capable to revert to a protoplast-like structure in the inner medulla.     

Ligation of the yolk sac circulation and its effect on the yolk sac ultrastructure and development of the rat fetus]

The effect of an interruption of the yolk sac circulation on the rat visceral yolk sac and the development of the fetoplacental unit was examined in the last third of pregnancy. The yolk sac ischaemia was induced by ligating the blood vessels of the yolk sac stalk which connect the vitelline circulation with that of the fetus. A 3-hour ligature caused an extensive swelling of most cell organelles in the epithelial cells and in the capillary endothelia of the yolk sac. Other structural changes were indicative of a cessation of pinocytosis. A 6-hour ligature resulted in a common increase of cell swelling and in a beginning disintegration of the endothelial cells lining the vitelline capillaries. A 15-hour ligature caused severe ultrastructural cell lesions and macroscopical alterations suggestive of a progressive necrolar finding of a nearly complete loss of the amniotic fluid and the death of the fetus, although the maternal blood flow appeared to be still intact in the placenta.     

Interhemispheric asymmetry of the hippocampal damage after bilateral ligation of common carotid arteries

Permanent bilateral occlusion of common carotid arteries in rats with different behaviour types led to non-uniform structural alterations in the hippocampus. In the majority of animals, morphological changes were diffuse (i.e. having no clear localisation in a definite region of the brain structure) and symmetrical (i.e. having no evident prevalence in one of the brain hemispheres). In 6.6% of survived animals, apart from diffuse structural changes, local and asymmetrical sites of lesions occurred in the hippocampus and mostly in the dorso-lateral thalamic nuclei of the right brain hemisphere. These local zones of strongly pronounced pathology corresponded to ischemic insults which were described earlier by other authors under transient cerebral ischemia. It is supposed that the occurrence of unilateral ischemic insults in a definite region of hippocampus and thalamus after bilateral occlusion of common carotid arteries is due to individual features of the anatomy of the vascular brain system which are found more frequently in rats with passive type of behaviour and in rats of the middle group than in rats with active type of behaviour.     

Autonomic control of the heart is altered in Sprague-Dawley rats with spontaneous hydronephrosis

The renal medulla plays an important role in cardiovascular regulation, through interactions with the autonomic nervous system. Hydronephrosis is characterized by substantial loss of renal medullary tissue. However, whether alterations in autonomic control of the heart are observed in this condition is unknown. Thus we assessed resting hemodynamics and baroreflex sensitivity (BRS) for control of heart rate in urethane/chloralose-anesthetized Sprague-Dawley rats with normal or hydronephrotic kidneys. While resting arterial pressure was similar, heart rate was higher in rats with hydronephrosis (290 ± 12 normal vs. 344 ± 11 mild/moderate vs. 355 ± 13 beats/min severe; P < 0.05). The evoked BRS to increases, but not decreases, in pressure was lower in hydronephrotic rats (1.06 ± 0.06 normal vs. 0.72 ± 0.10 mild/moderate vs. 0.63 ± 0.07 ms/mmHg severe; P < 0.05). Spectral analysis methods confirmed reduced parasympathetic function in hydronephrosis, with no differences in measures of indirect sympathetic activity among conditions. As a secondary aim, we investigated whether autonomic dysfunction in hydronephrosis is associated with activation of the renin-angiotensin system (RAS). There were no differences in circulating angiotensin peptides among conditions, suggesting that the impaired autonomic function in hydronephrosis is independent of peripheral RAS activation. A possible site for angiotensin II-mediated BRS impairment is the solitary tract nucleus (NTS). In normal and mild/moderate hydronephrotic rats, NTS administration of the angiotensin II type 1 receptor antagonist candesartan significantly improved the BRS, suggesting that angiotensin II provides tonic suppression to the baroreflex. In contrast, angiotensin II blockade produced no significant effect in severe hydronephrosis, indicating that at least within the NTS baroreflex suppression in these animals is independent of angiotensin II.     

Intra- and extraneuronal changes of immunofluorescence staining for TNF-alpha and TNFR1 in the dorsal root ganglia of rat peripheral neuropathic pain models

1. Several lines of evidence suggest that cytokines and their receptors are initiators of changes in the activity of dorsal root ganglia (DRG) neurons, but their cellular distribution is still very limited or controversial. Therefore, the goal of present study was to investigate immunohistochemical distribution of TNF-alpha and TNF receptor-1 (TNFR1) proteins in the rat DRG following three types of nerve injury. 2. The unilateral sciatic and spinal nerve ligation as well as the sciatic nerve transection were used to induce changes in the distribution of TNF-alpha and TNFR1 proteins. The TNF-alpha and TNFR1 immunofluorescence was assessed in the L4-L5 DRG affected by nerve injury for 1 and 2 weeks, and compared with the contralateral ones and those removed from naive or sham-operated rats. A part of the sections was incubated for simultaneous immunostaining for TNF-alpha and ED-1. The immunofluorescence brightness was measured by image analysis system (LUCIA-G v4.21) to quantify immunostaining for TNF-alpha and TNFR1 in the naive, ipsi- and contralateral DRG following nerve injury. 3. The ipsilateral L4-L5 DRG and their contralateral counterparts of the rats operated for nerve injury displayed an increased immunofluorescence (IF) for TNF-alpha and TNFR1 when compared with DRG harvested from naive or sham-operated rats. The TNFalpha IF was increased bilaterally in the satellite glial cells (SGC) and contralaterally in the neuronal nuclei following sciatic and spinal nerve ligature. The neuronal bodies and their SGC exhibited bilaterally enhanced IF for TNF-alpha after sciatic nerve transection for 1 and 2 weeks. In addition, the affected DRG were invaded by ED-1 positive macrophages which displayed simultaneously TNFalpha IF. The ED-1 positive macrophages were frequently located near the neuronal bodies to occupy a position of the satellites. 4. The sciatic and spinal nerve ligature resulted in an increased TNFR1 IF in the neuronal bodies of both ipsi- and contralateral DRG. The sciatic nerve ligature for 1 week induced a rise in TNFR1 IF in the contralateral DRG neurons and their SGC to a higher level than in the ipsilateral ones. In contrast, the sciatic nerve ligature for 2 weeks caused a similar increase of TNFR1 IF in the neurons and their SGC of both ipsi- and contralateral DRG. The spinal nerve ligature or sciatic nerve transection resulted in an increased TNFR1 IF located at the surface of the ipsilateral DRG neurons, but dispersed IF in the contralateral ones. In addition, the SGC of the contralateral in contrast to ipsilateral DRG displayed a higher TNFR1 IF. 5. Our results suggest more sources of TNF-alpha protein in the ipsilateral and contralateral DRG following unilateral nerve injury including macrophages, SGC and primary sensory neurons. In addition, the SGC and macrophages, which became to be satellites, are well positioned to regulate activity of the DRG neurons by production of TNF-alpha molecules. Moreover, the different cellular distribution of TNFR1 in the ipsi- and contralateral DRG may reflect different pathways by which TNF-alpha effect on the primary sensory neurons can be mediated following nerve injury.     

A Comparison of the Effects of Acrylamide and Experimental Diabetes on the Retrograde Axonal Transport of Proteins in the Rat Sciatic Nerve: Analysis by Two-Dimensional Polyacrylamide Gel Electrophoresis

Retrogradely transported proteins that accumulated for 18 h distal to a ligature on the sciatic nerve of rats were separated by two-dimensional polyacrylamide gel electrophoresis and visualised with silver stain. A total of 14 proteins were detectable in this way as being retrogradely transported. In rats rendered diabetic 14 days previously by a single intravenous dose of streptozotocin, the accumulation of four of those proteins was noticeably decreased. Administration of acrylamide to a cumulative dose of 150 mg.kg-1 or 350 mg.kg-1 decreased the accumulation of four and eight proteins, respectively. Three of the four protein changes were common to the diabetic and acrylamide-treated animals, and were present before signs of neuropathy could be detected. The results suggest that those alterations may play a causal role in the development of neuropathy.     

Ultrastructural abnormalities of muscle spindles in the rat masseter muscle with malocclusion-induced damage

Human temporomandibular disorders due to disturbed occlusal mechanics are characterized by sensory, motor and autonomic symptoms, possibly related to muscle overwork and fatigue. Our previous study in rats with experimentally-induced malocclusion due to unilateral molar cusp amputation showed that the ipsilateral masseter muscles undergo morphological and biochemical changes consistent with muscle hypercontraction and ischemia. In the present study, the masseter muscle spindles of the same malocclusion-bearing rats were examined by electron microscopy. Sham-operated rats were used as controls. In the treated rats, clear-cut alterations of the muscle spindles were observed 26 days after surgery, when the extrafusal muscle showed the more severe damage. The fusal alterations affected predominantly capsular cells, intrafusal muscle fibers and sensory nerve endings. These results suggest that in the malocclusion-bearing rats, an abnormal reflex regulation of the motor activity of the masticatory muscles may take place. They also allow us to hypothesize that muscle spindle alterations might be involved in the pathogenesis of human temporomandibular disorders.     

Intra- and Extraneuronal Changes of Immunofluorescence Staining for TNF- and TNFR1 in the Dorsal Root Ganglia of Rat Peripheral Neuropathic Pain Models

1. Several lines of evidence suggest that cytokines and their receptors are initiators of changes in the activity of dorsal root ganglia (DRG) neurons, but their cellular distribution is still very limited or controversial. Therefore, the goal of present study was to investigate immunohistochemical distribution of TNF-α and TNF receptor-1 (TNFR1) proteins in the rat DRG following three types of nerve injury.2. The unilateral sciatic and spinal nerve ligation as well as the sciatic nerve transection were used to induce changes in the distribution of TNF-α and TNFR1 proteins. The TNF-α and TNFR1 immunofluorescence was assessed in the L4-L5 DRG affected by nerve injury for 1 and 2 weeks, and compared with the contralateral ones and those removed from naive or sham-operated rats. A part of the sections was incubated for simultaneous immunostaining for TNF-α and ED-1. The immunofluorescence brightness was measured by image analysis system (LUCIA-G v4.21) to quantify immunostaining for TNF-α and TNFR1 in the naive, ipsi- and contralateral DRG following nerve injury.3. The ipsilateral L4-L5 DRG and their contralateral counterparts of the rats operated for nerve injury displayed an increased immunofluorescence (IF) for TNF-α and TNFR1 when compared with DRG harvested from naive or sham-operated rats. The TNFα IF was increased bilaterally in the satellite glial cells (SGC) and contralaterally in the neuronal nuclei following sciatic and spinal nerve ligature. The neuronal bodies and their SGC exhibited bilaterally enhanced IF for TNF-α after sciatic nerve transection for 1 and 2 weeks. In addition, the affected DRG were invaded by ED-1 positive macrophages which displayed simultaneously TNFα IF. The ED-1 positive macrophages were frequently located near the neuronal bodies to occupy a position of the satellites.4. The sciatic and spinal nerve ligature resulted in an increased TNFR1 IF in the neuronal bodies of both ipsi- and contralateral DRG. The sciatic nerve ligature for 1 week induced a rise in TNFR1 IF in the contralateral DRG neurons and their SGC to a higher level than in the ipsilateral ones. In contrast, the sciatic nerve ligature for 2 weeks caused a similar increase of TNFR1 IF in the neurons and their SGC of both ipsi- and contralateral DRG. The spinal nerve ligature or sciatic nerve transection resulted in an increased TNFR1 IF located at the surface of the ipsilateral DRG neurons, but dispersed IF in the contralateral ones. In addition, the SGC of the contralateral in contrast to ipsilateral DRG displayed a higher TNFR1 IF.5. Our results suggest more sources of TNF-α protein in the ipsilateral and contralateral DRG following unilateral nerve injury including macrophages, SGC and primary sensory neurons. In addition, the SGC and macrophages, which became to be satellites, are well positioned to regulate activity of the DRG neurons by production of TNF-α molecules. Moreover, the different cellular distribution of TNFR1 in the ipsi- and contralateral DRG may reflect different pathways by which TNF-α effect on the primary sensory neurons can be mediated following nerve injury.     

A heterogeneous immunofluorescence staining for laminin-1 and related basal lamina molecules in the dorsal root ganglia following constriction nerve injury

The bodies of primary sensory neurons and their satellite glial cells (SGCs) are limited by the basal laminae from extracellular matrix of the dorsal root ganglia (DRG). The basal laminae displayed uniform immunofluorescence staining for laminin-1 in the sections of rat intact (naive) DRG. A proximal or distal ligature of the spinal nerves resulted in a heterogeneous immunostaining for laminin-1 around neuron-SGC units in the sections of the corresponding DRG. The pattern of irregular laminin-1 immunofluorescence was more extensive in the ipsilateral than the contralateral DRG of the operated rats. The immunofluorescence for laminin-1 exactly coincided with binding of Concanavalin-A as well as immunostaining for type IV collagen in both naive DRG and DRG affected by nerve ligature. Nidogen immunostaining decreased or fully disappeared at the surface of the SGCs consistently with immunofluorescence staining for laminin-1, but retained or increased in the endothelial cells and ED-1 positive cells invaded the DRG affected by nerve ligature. The results indicate an alteration of the content of basal laminae surrounding the bodies of primary sensory neurons and their SGSs following nerve constriction injury. A modulation of the basal laminae may be related with other cellular and molecular alterations related with peripheral neuropathic pain, for example, expansion of sympathetic sprouts.     

Modifications of arterial pressure and plasma renin: their effects on the norepinephrine content of hypothalamus and medulla oblongata.

The effects of the bilateral nephrectomy and acute hypotension caused by the cava vein ligature on the norepinephrine (NE) concentration in hypothalamus and medulla oblongata and on the plasma renin activity were studied in male rats. NE increased and plasma renin activity decreased in hypothalamus in 24 h nephrectomized rats with or without the ligatures of the cava vein. NE also decreased in medulla of groups with the ligatures only. The mean arterial pressure, did not correlate with the NE or plasma renin activity levels. The modifications of the NE in the central nervous system showed an inverse relationship with plasma renin activity and this, could be due to changes in the NE uptake and/or release caused by the plasma renin activity alterations. NE modifications do not seem to be caused directly through reflex of the arterial pressure.     

Lowered plasma erythropoietin in hypoxic rats with kidney tubule lesions

The role of the kidney tubules in the renal formation of erythropoietin is incompletely understood. Therefore, the capability to produce erythropoietin in response to hypoxia was studied in rats with tubular lesions. Nephron damage was induced in two different ways. First, rats were treated with the nephrotoxic aminoglycoside gentamicin (67.5 mg/kg and day) for 14 days. The animals were then subjected to simulated altitude (6,800 m) for 6 h. The resulting plasma erythropoietin concentration was significantly lower (0.5 IU/ml) than in saline treated control rats exposed to hypoxia (1.0 IU/ml). Second, unilateral hydronephrosis was induced by ureteral ligation. The contralateral kidney was removed immediately before the animals were exposed to simulated altitude for 6 h. The plasma erythropoietin concentration in the ureter-ligated rats did not increase above the value (0.3 IU/ml) in hypoxia exposed anephric rats. These results indicate that the production of erythropoietin is reduced following tubular injury. Tubule cells may directly produce the hormone or interfere with the O2-sensing mechanisms controlling its synthesis. The latter hypothesis would seem to be supported by our failure to demonstrate in vitro erythropoietin production by the two established kidney tubule cell lines, LLC-PK1 and PK-15.     

Urolithiasis associated with experimental lymphocytic choriomeningitis virus inoculation in Lewis rats

A high frequency of struvite urolithiasis, hydronephrosis, and other urinary tract lesions developed in a group of Lewis rats inoculated intracranially with lymphocytic choriomeningitis virus (LCMV). Initially, clinically ill rats were referred to necropsy: 30 rats over 3 years. These rats had high frequency of urolithiasis (8/30, 27%), hydronephrosis (12/30, 40%), cystitis (9/30, 30%), transitional cell carcinoma (4/30, 13%), and pyelonephritis (19/30, 63%). Lesions were more common in LCMV-inoculated rats. After this trend was noted, all rats on this protocol were necropsied as part of a cohort study (n = 144). Although the apparent frequency of disease was lower due to increased sampling, there still was a high number of urolithiasis (9/144, 6%) and hydronephrosis (40/144, 28%) cases. All cases of urolithiasis developed in rats inoculated with LCMV (9/44, 20%), as did most cases of hydronephrosis (31/44, 70%). Although sham-injected and uninoculated control rats also had high frequency of hydronephrosis (6/57 [11%] and 3/43 [7%], respectively), LCMV-inoculated rats had a significantly higher frequency of disease than did sham inoculated (P < 0.0001) and uninoculated (P < 0.0001) controls. These results suggest that Lewis rats may be predisposed to developing lesions of the urinary tract, and that intracranial inoculation of rats with LCMV augments this tendency, leading to formation of struvite calculi and associated urinary tract disease.     

Alcohol-hexobarbital interaction in rats under acute stress.

In male Sprague-Dawley rats, one hour stress (unilateral hindleg ligature) and 3 g/kg ethanol (oral intubation) in combination inhibited $\text{in vitro}$ liver hexobarbital (HB) metabolism to a greater extent than either treatment alone. These treatments produced analogous effects on plasma HB disappearance $\text{in vivo}$. Ethanol alone or in combination with stress also increased HB sleep time. But stress alone or with ethanol reduced the HB sleep time, results which suggest that sleep time is not a reliable index of metabolism in stressed rats. This study shows that the effects of acute stress and alcohol on HB metabolism are additive.     

两种早期心衰大鼠模型的建立和心功能的比较

目的比较两种不同方法建立大鼠心衰模型心功能的特点,寻找大鼠模型早期心衰阶段。方法用冠脉结扎法及腹主动脉结扎法建立不同的心衰模型,用血流动力学及心脏称重的方法比较其心功能的各项指标。结果冠脉结扎组术后2周没有心功能的改变,2周后收缩和舒张功能均下降,4周达最低。腹主动脉结扎组术后14周没有心功能的下降,16周出现了舒张功能的衰竭。结论冠脉结扎法及腹主动脉结扎法均可以造成早期心衰,冠脉结扎法术后2周为早期心衰阶段,2周后同时出现收缩和舒张功能衰竭,腹主动脉结扎法术后14周为早期心衰阶段,14周后出现了舒张功能衰竭。     

Liver ultrastructural changes following portal circulation disturbances

Liver cell changes produced in rats by the ligature of the portal vein and of the spleen pedicle were studied by electron microscopy. There were differences in the liver response to the various types of circulatory disturbances. The earliest and most marked lesions of hepatic cells were noticed in the case of portal vein ligature, and occurred at the level of rough endoplasmic reticulum, mitochondria and lysosomes. No significant changes in Kupffer cells. When the spleen pedicle was ligated, the hepatic cell changes were less obvious, but the Kupffer cells changes were more prominent, testifying and increased hetero- and autophagy.     

Hydronephrosis in ACI/N rats

Of 45 ACI/N rats 9 were found with renal agenesis and 2 with hydronephrosis. The hydronephrosis may have been due to faulty development of the mesonephric duct.     

Repression of apurinic/apyrimidinic endonuclease by p53-dependent apoptosis in hydronephrosis-induced rat kidney

p53 plays a major role in apoptosis through activation of pro-apoptotic gene Bax. It also regulates apurinic/apyrimidinic endonuclease (APE) expression in the base excision repair pathway against oxidative DNA damages. This study investigated whether p53-dependent apoptosis is correlated with APE using an experimental rat model of hydronephrosis. Hydronephrosis was induced by partial ligation of the right ureter. Animals were sacrificed on scheduled time after unilateral ureteral obstruction and the expression of 8-OHdG, γ-H2AX, apoptotic proteins and APE was determined. The accumulated p53 activated Bax and caspase-3 7 days after hydronephrosis induction and the resulting high levels of p53-dependent apoptotic proteins and γ-H2AX tended to decrease APE. The intensities of 8-OHdG and caspase-3 immunolocalization significantly increased in obstructed kidneys than in sham-operated kidneys, although APE immunoreactivity increased after hydronephrosis induction. These results suggest that oxidative DNA damages in obstructed kidneys may trigger p53-dependent apoptosis through repression of APE.     

Splanchnic and systemic hemodynamic alterations in chronic, progressive portal hypertensive rats

Systemic and splanchnic hemodynamics were studied by using the radioactive microsphere technique, in rats in which a chronic and progressive portal or intrahepatic hypertension was produced by the placement of a nonconstricting, well fitted ligature around the portal or suprahepatic vein when the rat weighted about 100 g. The hemodynamic measurements were performed 80-90 days after ligature placement. Suprahepatic ligated rats presented portal and intrahepatic hypertension, but nonportal-systemic shunts (PSS). The only hemodynamic disturbance observed was a decrease in renal blood flow. Portal ligated rats showed a wide range of PSS and were divided in two subgroups. The subgroups with high PSS rate (greater than 10%) showed increased cardiac output and plasma renin content, as well as decreased splanchnic blood flow, portal venous inflow, hepatic blood flow and renal blood flow. Low portal-systemic shunts subgroups showed decreased cardiac output while its distribution was similar to the control rats. There was no correlation between portal pressure and shunt rate. Low shunt groups, furthermore, showed increased levels of plasma renin concentration.