PubMed HealthSearch

Biomedical subjects

R J Sutherland

Publications and source records attributed to R J Sutherland.

At least 19 recordsLinked to original sources

Noradrenaline depletion blocks behavioral sparing and alters cortical morphogenesis after neonatal frontal cortex damage in rats.

The possibility that cortical noradrenaline (NA) is necessary for sparing of function that occurs after neonatal frontal cortex damage was examined. Spatial localization by rats with frontal cortex damage on postnatal day 7 (P7) was better than that by rats with similar damage sustained as adults. The sparing was abolished in rats depleted of cortical NA by means of neonatal 6-hydroxydopamine (6HDA) administration. The blockade of sparing in the P7 frontal operates was associated with a smaller brain, thinner cortex, and reduced cortical dendritic branching relative to saline-treated P7 frontal operates. NA depletion alone in unoperated rats did not affect spatial learning but did reduce brain size and dendritic branching. Rats with frontal lesions on P4 did not show sparing of spatial localization, and 6HDA administration had no additional behavioral effect. Overall, these data are consistent with the notion that NA has some general function in maintaining some forms of plasticity in posterior cortex.

Animals

Assessment of the potential toxicity of a poison for rabbits, pindone (2-pivalyl 1, 3 indandione), to domestic animals.

The toxicity of pindone, a rabbit poison, to horses, cattle, goats, chickens, dogs and cats was investigated, using extension of prothrombin time (PT) as an index of poisoning. The daily dose of pindone, administered for 5 days, ranged from 0.3 mg/kg for dogs to 2.5 mg/kg for chickens. This range of dose rates was considered to be indicative of the worst possible case that could arise following a campaign of baiting for rabbits. Although significant elevations in PT (more than double baseline values) were noted in all species other than horses, clinical signs of anticoagulant poisoning were not observed in any of the species tested. From the observed PT, cattle and cats appeared to be the most susceptible, and horses the least susceptible, to pindone toxicity. The half-lives of the elevated PT were calculated as 3.1 days for cattle, 2.8 days for goats and chickens, 1.9 days for horses and dogs and less than one day for cats. It is proposed that these half-lives can be used as a guide for determining the duration of treatment of pindone-affected animals.

Animals

Domoic acid, an environmental toxin, produces hippocampal damage and severe memory impairment.

Microinjections of domoic acid, a presumed shellfish toxin, into the hippocampal formation of rats produces degeneration of CA3 and CA1 pyramidal cells and dentate gyrus granule cells. We demonstrate that domoate-treated rats exhibit a long-lasting anterograde amnesia for spatial information in the Morris water task. This preparation provides a good model for examining neurotoxicity and the anterograde amnesic syndrome observed in humans following consumption of domoate-contaminated shellfish.

Amnesia

Hereditary nephritis in the bull terrier: evidence for inheritance by an autosomal dominant gene.

A high prevalence of renal failure has been reported in bull terriers in Australia. The pattern of inheritance was analysed in a family of 33 bull terriers in which 10 dogs had renal disease manifested by proteinuria, ultrastructural abnormalities in the glomerular basement membrane, renal failure, or 'end stage' kidneys. The presence of at least one affected parent for each affected offspring, the approximately equal male/female ratio and the apparent absence of 'generation-skipping', strongly supported an autosomal dominant mode of inheritance, assuming a fully penetrant single major gene locus. Further evidence was not compatible with either an autosomal recessive or X-linked inheritance pattern. This contrasts with the X-linked inheritance shown in Alport's-type human hereditary nephritis and hereditary glomerulopathy in the samoyeds. Hereditary nephritis in the bull terrier should be a useful model for non-Alport's-type human hereditary nephritis, which is also reported to have an autosomal dominant inheritance pattern.

Animals

Hippocampus, amygdala, and memory deficits in rats.

Five experiments were conducted to compare the contribution of the hippocampal formation and amygdala to mnemonic processes. The performance of rats with damage to the hippocampal formation or amygdala was examined in tests of visual and olfactory non-matching-to-sample with familiar items, cross-modal association, gustatory neophobia, topographical memory, autonomic conditioning to context, and configural discriminations. Neither lesion affects non-matching-to-sample performance. An intact hippocampal formation, but not amygdala, is necessary for cross-modal association between vision and olfaction, topographical memory, conditioning to context, and configural discrimination learning. Amygdala damage disrupted gustatory neophobia and may have impaired learning an association between an auditory cue and food reward.

Amygdala

Induction of diabetes in PVG/c strain rats by manipulation of the immune system.

A combination of thymectomy and sublethal irradiation (Tx-X) consistently induced diabetes in female rats of the PVG/c strain. The incidence of diabetes varied from 10.7% to 53.4% in seven successive Tx-X groups (mean 29.7%). Both clinical and subclinical disease was observed with the majority of affected animals developing the former condition. This was acute in onset, rapidly fatal (1-4 days) and characterized by ketosis and lipidemia. Overtly diabetic rats had markedly raised plasma glucose concentrations compared to normal rats of the same strain and plasma immunoreactive insulin concentrations were correspondingly depressed in this group. Histopathological change within the islets of Langerhans correlated with clinical status and ranged from diffuse atrophy in the majority of the acutely diabetic rats to mild and focal lymphocytic insulitis in a proportion of the non-diabetic rats. Islet cell autoantibodies were demonstrated by indirect immunofluorescence in approximately 25% of clinically diabetic animals. The majority of diabetic rats were found to be responsive to insulin and the clinical signs could be reversed by daily parenteral insulin administration. These observations implicate the immune system in diabetes generation and are consistent with an immune mediated pathogenesis as the underlying cause of the islet cell destruction. This syndrome may thus be a potentially useful animal model for type 1 (insulin dependent) diabetes in man.

Animals

The hippocampal formation is necessary for rats to learn and remember configural discriminations.

A negative patterning discrimination problem was arranged by reinforcing rats for bar pressing when either a light or tone was presented (L+/T+) but not reinforcing the response when the compound stimulus, light and tone, was presented (LT-). To solve this problem, the animal must be able to construct a unique configural representation of the compound that can be distinguished from the representations of the individual elements. We have proposed that the hippocampal formation is essential for the acquisition and retention of associations involving configural representations. Thus, our theory predicts that animals with hippocampal formation damage will not learn the negative patterning problem and that animals who learned this problem before receiving hippocampal formation damage will not retain the solution. These predictions were confirmed by the results of two experiments. The animals with hippocampal formation damage were unable to solve the negative patterning problem. These animals were able to solve a simple discrimination in which responding in the presence of a light was rewarded but responding in the presence of a tone was not rewarded. These results are discussed in relation to several other theories of hippocampal formation function.

Animals

The role of the fornix/fimbria and some related subcortical structures in place learning and memory.

Place learning and memory were assessed in rats with selective damage to the fornix/fimbria or to subcortical structures which have a major connection with the hippocampal formation via the fornix/fimbria. Navigation to a hidden or visible platform in a fixed location was studied in the Morris water task in rats who were preoperatively trained in the task or who were preoperatively naive. All rats learned to navigate accurately to a visible platform. Only complete transection of the fornix/fimbria abolished both acquisition and retention of navigation to a hidden platform. Severe impairment of postoperative acquisition was produced by bilateral damage to the medial nucleus accumbens or bilateral damage to the anterior thalamic area. Nucleus accumbens or anterior thalamic damage produced little effect on retention of preoperatively acquired place navigation. Damage to medial septum or mammillary complex produced modest impairments evident only in postoperative acquisition.

Animals

Hippocampal granule cells are necessary for normal spatial learning but not for spatially-selective pyramidal cell discharge.

The effects of massive destruction of granule cells of the fascia dentata on the spatial and temporal firing characteristics of pyramidal cells in the CA1 and CA3 subfields of the hippocampus were examined in freely moving rats. Microinjections of the neurotoxin colchicine were made at a number of levels along the septo-temporal axis of the dentate gyri of both hemispheres, resulting in destruction of over 75% of the granule cells. By contrast there was relatively little damage to the pyramidal cell fields. As assessed by three different behavioral tests, the colchicine treatment resulted in severe spatial learning deficits. Single units were recorded from the CA1 and CA3 subfields using the stereotrode recording method while the animals performed a forced choice behavioral task on the radial 8-arm maze. Considering the extent of damage to the dentate gyrus, which has hitherto been considered to be the main source of afferent information to the CA fields, there was remarkably little effect on the spatial selectivity of "place cell" discharge on the maze, as compared to recordings from control animals. There was, however, a change in the temporal firing characteristics of these cells, which was manifested primarily as an increase in the likelihood of burst discharge. The main conclusion derived from these findings is that most of the spatial information exhibited by hippocampal pyramidal cells is likely to be transmitted from the cortex by routes other than the traditional "trisynaptic circuit". These routes may include the direct projections from entorhinal layers II and III to CA3 and CA1, respectively.

Animals

Damage to the hippocampal formation in rats selectively impairs the ability to learn cue relationships.

We assessed the contribution of the hippocampal formation to performance in tasks that require rats to respond to a relationship between discriminative stimuli. The first experiment employed a nonmatching-to-sample procedure in a Y-maze. Three pairs of boxes were used which differed in brightness of the walls and in the odors that they contained. The rats were trained prior to receiving kainic acid and colchicine-induced damage to the hippocampal formation or electrolytic damage to the amygdala. After surgery all rats performed the nonmatching-to-sample task accurately if both brightness and odor cues were present in the sample and choice boxes or if the boxes contained either visual cues alone or odor cues alone. If the available cue modality was different in sample and choice boxes, then the amygdala-damaged, but not the hippocampal-damaged, rats performed accurately. In the second experiment control rats or rats with hippocampal formation damage were trained postoperatively in a conditional black/white discrimination task in a Y-maze. Only the control group successfully learned to select the white arm if the start box was illuminated and the black arm if the start box was dark. Subsequently, both groups learned a simple black/white discrimination. The same rats were tested in the hidden platform version of the Morris water task and only the control group learned to swim accurately to the goal. Both groups learned to swim accurately to a visible black platform. The results are consistent with the notion that the hippocampal formation is essential to learning that involves control exerted by a configural relationship among cues, independently of the spatial or conditional requirements of tasks.

Amygdala

Biochemical evaluation of the hepatobiliary system in dogs and cats.

The causes and clinical signs of hepatobiliary involvement in disease are many and varied and often are not referable directly to this organ system. Laboratory investigation frequently is necessary to rule hepatic disease in or out, to assess the functional impact on the liver, and to decide whether hepatic disease is the patient's primary problem or a complication of something else. The selection and interpretation of laboratory tests to resolve these problems is based on an understanding of relevant functional anatomy and pathophysiology. The mainstay of such assessment is hepatic enzymology, which can detect active disease in both hepatocytes and the biliary system. The hepatocellular pattern of disease is characterized by increases in leakage enzymes such as SDH, GLDH, and ALT and the cholestatic pattern by increases in induced enzymes (ALP and GGT). In general, enzymology does not allow the intensity or functional effect of hepatobiliary disease to be assessed, and quite severe hepatopathies may have only minimal enzyme abnormalities. For this reason, the primary biochemical data base for ruling hepatobiliary disease in or out always should involve some screening tests of hepatic function, such as albumin, protein, bilirubin, glucose, or urea determinations; as well as urinalysis to search for bilirubinuria and urobilinogenuria in hyperbilirubinemic patients and for ammonium biurate crystals when hyperammonemia or hepatic encephalopathy is suspected. Because the liver synthesizes most clotting factors, evaluation of blood coagulation is indicated when surgery is contemplated on patients with liver disease or when bleeding is present. Paired pre- and post-prandial determinations of serum bile acids are the preferred method for assessment of hepatobiliary function in dogs and cats. However, the BSP clearance test continues to be useful in the functional assessment of the liver as long as the dye remains available to veterinarians. Clearance of BSP is delayed in hepatocellular, cholestatic, and portosystemic disease as well as by severe extrahepatic circulatory disturbances, In general, this functional test is less sensitive than serum bile acids or the ammonia tolerance test in the recognition of hepatic encephalopathy caused by portosystemic anomalies. The objectives of biochemical screening of the liver are to establish the type (hepatocellular, biliary, or mixed), duration (acute, chronic), and stage (aggressive, convalescent) of hepatobiliary disease and to assess functional status.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Salinomycin poisoning in point-of-lay turkeys.

Salinomycin poisoning occurred in a flock of 700 point-of-lay turkeys; 400 birds died over 7 days as a result of consuming feed contaminated with 50 ppm salinomycin. No gross lesions were detected. Histologic evidence of a myopathy was most readily detected in leg muscles of turkeys 5 to 7 d after ingesting salinomycin. Feeding trials were undertaken and individual susceptibility to the drug was found to vary greatly. In affected birds the plasma concentrations of creatine kinase (CK) and aspartate aminotransferase (AST) were found to be in the range of 500,000 to 2,500,000 IU/l and 9000 to 25,000 IU/l, respectively. The marked increase in the plasma activities of these enzymes preceded histological evidence of segmental muscle necrosis.

Animal Feed

Functional and morphological studies on blood platelets in a thrombasthenic horse.

A four-year-old Standardbred gelding presented with a 3.5 year history of intermittent epistaxis and spontaneous submucosal petechiae and ecchymoses in the nares and the mouth. Routine haematological and biochemical examinations were unremarkable. A thrombocytopathy was suspected when activated partial thromboplastin time, one stage prothrombin time, plasma fibrinogen and the platelet count were all normal. The patient's platelets failed to aggregate with serotonin, adenosine diphosphate, collagen (at 20 micrograms/ml) or the endoperoxide analogue U46619. Very high levels of collagen (100 micrograms/ml) did cause aggregation. The response to the calcium ionophore A23187 was reduced and although complete degranulation occurred the resulting aggregates were unstable. Thromboxane generation in response to collagen and ADP was inferred from the concentration of its stable metabolite thromboxane B2 and was reduced. A diagnosis of a thrombasthenia-like syndrome possibly equivalent to Type II Glanzmann's thrombasthenia in people was made.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5

Contributions of cingulate cortex to two forms of spatial learning and memory.

The contribution of anterior and posterior cingulate cortical areas to spatial learning and memory was examined in 4 experiments using the place-navigation task. Rats with complete bilateral cingulate cortex aspiration or aspiration of posterior cingulate cortex (area 29) alone could not swim directly to a hidden platform located in a fixed place. When animals with these lesions were tested for 40 d in a place-alternation task in which they received 16 daily trials with the platform placed in a new location each day, they did not show reliable improvement in place navigation. The inability to swim to changing locations or to a single location was not overcome by preoperative training in these tasks. Rats with anterior cingulate cortex aspirations showed a less severe impairment in both tasks and, with more training than is necessary for control rats, they acquired near-normal place-navigation accuracy. Rats with complete cingulate cortex aspiration were almost as accurate as control rats in learning to swim to a visible platform. The results imply that posterior cingulate areas play an essential role in the use of topographical information, probably by transmitting and elaborating information passing between the hippocampal system and neocortical association areas.

Animals

Effects of neonatal forebrain noradrenaline depletion on recovery from brain damage: performance on a spatial navigation task as a function of age of surgery and postsurgical housing.

The experiments examined the contributions of forebrain noradrenaline and environmental enrichment to recovery of place navigation ability in rats after hemidecortication in infancy or adulthood. Noradrenaline depletion did not affect recovery from neonatal hemidecortication, although the early hemidecortications did allow sparing of function relative to adult operates. Noradrenaline depletion also failed to attenuate the positive effects of enriched housing on otherwise normal rats. Noradrenaline depletion did retard recovery of adult hemidecorticate rats housed in standard laboratory cages, but it did not retard recovery of adult hemidecorticate rats housed in enriched environments. The results suggest that noradrenaline is importantly involved in enhancing recovery from brain damage when other sources of compensation (e.g., neonatal injury, enriched environment) are absent.

Animals