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Biomedical subjects

B T Volpe

Publications and source records attributed to B T Volpe.

At least 19 recordsLinked to original sources

Early post-natal administration of 5,7-dihydroxytryptamine destroys 5-HT neurons but does not affect spatial memory.

The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) may play an important role in learning and memory. It has also been suggested that 5-HT abnormalities may mediate some aspects of the cognitive disorders associated with Korsakoff syndrome and Alzheimer's Disease. The effect of intracisternally applied 5-HT neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT) on learning and memory in rodents was evaluated. Three-day-old rat pups were treated with pargyline (40 mg/kg, i.p.) followed by 5,7-DHT (50 micrograms/pup) and returned to the dam for a month. At 75 days of age, rats were tested on a learning set problem in the Morris water maze for 5 days followed by 30 days of testing in a 12-arm radial maze with 8 of the 12 arms baited. In the Morris water maze, the latency to locate the hidden platform did not differ significantly for 5,7-DHT treated and control rats (F less than 1.0). Similarly, 5,7-DHT treated rats performed comparably to controls on the 12-arm radial maze (F less than 1.0). At 106 days of age the assay of tryptophan hydroxylase activity in the dorsal raphe nuclei and hippocampus showed marked reduction (86%, 78%, respectively) in 5,7-DHT treated animals compared to vehicle injected controls. Immunocytochemical analysis was consistent with the biochemical results. In 5,7-DHT treated animals there was severe loss of neurons that bind 5-HT antibody in the dorsal and medial raphe nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine

Loss of hippocampal CA1 pyramidal neurons correlates with memory impairment in rats with ischemic or neurotoxin lesions.

Rats were trained for 20 days in a modified T maze to perform an invariant, tactile discrimination and a variable, delayed spatial discrimination, and then were exposed either to 30 min of transient forebrain ischemia or to low- or high-dose ibotenic acid to damage the dorsal hippocampus bilaterally. Only rats exposed to ischemia or high-dose ibotenic acid demonstrated impaired performance during 30 postoperative test days on both aspects of the task (p less than .05). Volume of hippocampal damage did not predict performance. However, the extent of CA1 pyramidal neuron loss correlated significantly with performance on the delayed spatial discrimination (p less than .01). Damage to the dentate gyrus and CA2-3 did not correlate with performance. These results support the view that the hippocampus, in particular the CA1 region, is crucial for certain types of memory performance.

Animals

In situ hybridization analysis of c-fos and c-jun expression in the rat brain following transient forebrain ischemia.

Early induction of the mRNAs encoding the c-Fos and c-Jun nuclear proteins was examined in rat brain by in situ hybridization at various timepoints following global forebrain ischemia by the method of four-vessel occlusion. All animals were subjected to 20 min of transient ischemia. This produced a pattern of proto-oncogene activation that was most intense in the granule cells of the dentate gyrus 30 min after ischemia, while the hilar cells in the dentate and the pyramidal cells of the CA3 region in the hippocampus showed a more delayed but robust expression of these immediate early genes at 1 h. The neurons of the CA1 region exhibited a more moderate hybridization signal at 1-2 h postischemia. Very little hybridization signal for either immediate early gene could be detected in animals perfused with fixative immediately following ischemia, suggesting that cellular energy levels may have to be restored to a certain level before efficient de novo mRNA synthesis can occur. In the cerebellum, a similar temporal pattern was observed: the granule cells exhibited a prompt but patchy expression of c-fos and c-jun that was followed by a delayed signal in the Purkinje cells. Without exception c-fos and c-jun appeared to be expressed in unison, although the time course of c-fos and c-jun mRNA accumulation and decay was different in various brain regions: invariably the cerebellum returned rapidly to its baseline with virtually no remaining signal at 3 h postischemia, while c-fos and c-jun activation in the hippocampus remained high at 3 h and returned to baseline by 6 h. Several other brain regions showed early production of c-fos and c-jun mRNAs, such as the medial habenula, piriform cortex, the amygdala, the centromedian, lateral posterior, paracentral, intermediodorsal and reuniens nuclei of the thalamus and the ventromedial and dorsal nuclei of the hypothalamus; in the brainstem, the trapezoid body and the noradrenergic neurons of the locus ceruleus as well as the adrenergic neurons in the ventrolateral medulla (C1 group) and nucleus tractus solitarius (C2 group) regions displayed slightly less intense hybridization signals. In addition, the ependyma of the lateral ventricles and the third ventricle showed a prompt albeit short-lived production of c-fos and c-jun mRNAs. Sham-operated animals as well as animals that had survived to one week postischemia showed either no or only trace levels of hybridization signal.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Hypersensitivity pneumonitis associated with a portable home humidifier.

Hypersensitivity pneumonitis (HP) is an immunologically mediated inflammatory disorder of the pulmonary parenchyma which has been traditionally associated with the inhalation of organic dusts (farmer's lung, pigeon breeder's disease) and a variety of simple chemical compounds. More recently, the disease has been reported in association with the inhalation of aerosolized droplets in home and office settings. In Connecticut, the home and office, rather than the farm or factory, are the most common, although frequently unrecognized, environmental settings in which HP develops. We report here a case of a young, healthy woman who developed severe HP associated with the use of a portable home ultrasonic humidifier. This clinical entity should be suspected in the patient with a "recurrent viral illness" or "recurrent pneumonia." A review of the clinical and laboratory findings of humidifier-induced HP are discussed in relation to its pathogenesis, diagnosis, and treatment.

Adult

Allocentric spatial and tactile memory impairments in rats with dorsal caudate lesions are affected by preoperative behavioral training.

Rats with caudate lesions and pretrained for 36 trials demonstrated impaired performance on the "reference memory" or invariant aspect of a 12-arm radial maze and normal performance on the "working memory" or variable aspect of the maze. Rats with caudate lesions and no pretraining were also impaired on an invariant tactile discrimination in a T maze, but they were not impaired on the variable goal-arm choice of the T maze. More extensive preoperative training ameliorated behavioral deficits of rats with caudate lesions in the T maze and radial arm maze. Results showed that behavioral impairment after damage to the caudate is not restricted to egocentric tasks as previously suggested, but the caudate seems to be involved in the initial acquisition of information that is invariant over many trials.

Animals

Preoperative training modifies radial maze performance in rats with ischemic hippocampal injury.

Rats exposed to 30 minutes of four-vessel occlusion reliably develop severe bilateral CA1 hippocampal injury; under certain conditions of radial maze training, such rats perform the reference memory component as well as controls yet perform the working memory component worse than controls. Reference memory is thought to depend on invariable and working memory on variable spatial information. We assessed the effect of training before ischemia. In Experiment 1, rats trained for 36 trials on 12-arm radial mazes before ischemia demonstrated a persistent impairment on the working memory task but eventually performed the reference memory task comparable to controls. Ischemic rats made more working memory errors as the number of choices increased. This pattern of working memory errors was similar to that in controls except, as expected, ischemic rats made many more errors. In Experiment 2, training for 80 trials before ischemia in rats decreased the severity of both the working and the reference memory impairment. Ischemia did not affect motor behavior in either experiment. These results characterize the working memory deficit in ischemic rats and demonstrate the importance of experimental factors, particularly in the design of treatment strategies to reduce functional impairments caused by ischemia.

Analysis of Variance

Confusional states following posterior cerebral artery infarction.

Four patients with left-sided posterior cerebral artery infarction developed acute confusional states. Fifteen additional patients with confusion following unilateral posterior cerebral artery infarction were identified from a review of the literature; in 14 the lesion was left sided. Destruction or disconnection of dominant hemisphere neocortex from limbic structures, resulting in impairment of focal attention, loss of linguistically organized memory, and/or disruption of temporal sequencing may be responsible for this syndrome.

Acute Disease

Selective loss of complex-pitch or speech discrimination after unilateral lesion.

Twenty-eight right-handed patients who suffered a single cerebrovascular accident in the distribution of either the left or right middle cerebral artery were tested on their ability to discriminate complex-pitch and speech stimuli presented dichotically. Whereas the left hemisphere lesion group was impaired in dichotic speech but not in dichotic complex-pitch discrimination, the right hemisphere lesion group was impaired in dichotic complex pitch but not in dichotic speech discrimination. Complex-pitch phenomena may provide a useful model for the study of auditory function in the nondominant hemisphere.

Attention

Modified T-maze training demonstrates dissociated memory loss in rats with ischemic hippocampal injury.

Rats were trained for 20 days on a modified T-maze which required discrimination of a stem choice that was invariant and a goal choice that alternated. Animals were then exposed to 30 min of transient severe forebrain ischemia (postischemic, PI animals), 30 min of less severe ischemia (non-criterion ischemic, NCI animals), or sham operations (controls). After 30 postoperative days, all animals were returned to the maze for an additional 30 trials. PI rats demonstrated a dissociated performance on stem and goal choice. Specifically, the PI animals were significantly impaired on discrimination of a goal choice, yet performed comparably to controls on discrimination of a stem choice. Impaired goal choice for PI animals was not due to differential run times, proactive interference, or interaction between goal and stem choice. Histopathologic analysis of PI animals revealed bilateral destruction of the pyramidal neurons in the dorsal CA 1 region of the hippocampus and lesser damage in the anterodorsal subiculum and the dorsolateral caudate. NCI animals had patchy variable ischemic neuronal damage. These data suggest that ischemic-induced bilateral CA 1 pyramidal neuron loss is sufficient to cause dissociated performance in trained animals on a T-maze, but that less severe ischemia does not cause reproducible hippocampal neuron damage or functional deficits. Further, the data extends the development of reliable behavioral measures for an animal model of the amnesic syndrome that may occur in humans after cardiac arrest.

Amnesia

Amnesia and second language learning.

The ability of an anterograde amnesic C.S. to learn a second language is assessed. First, her claim that she learned Italian while amnesic was examined in a series of formal tests of Italian. Second, C.S. and her husband were tutored in French and her acquisition was compared to that of her husband's. Third, C.S.'s ability to learn other kinds of verbal material with practice was investigated. The implications of C.S.'s apparent ability to learn a second language in the presence of a severe deficit for memory for other kinds of verbal material is discussed.

Amnesia

Memory strategies with brain damage.

The ability of anterograde amnesics with and without a history of alcoholism and patients with frontal lobe damage to think about memory, memorizing, and remembering was assessed. Alcoholic Korsakoffs' and frontal lobe patients' knowledge and use of memory strategies was deficient when compared with controls whereas nonalcoholic amnesics' was not. The use of the categorization mnemonic was assessed in a verbal learning experiment. Frontal lobe patients failed to spontaneously categorize a categorizable word list when trying to memorize it. Nevertheless, when forced to categorize the list, they benefited from the imposed structure. Nonalcoholic amnesics spontaneously categorized the list and benefited from the resulting organization.

Alcohol Amnestic Disorder

More on recognition and recall in amnesics.

Hirst et al. (1986) reported that amnesic forced-choice recognition was relatively preserved when compared with amnesic recall. They equated normal recognition and amnesic recognition by extending exposure time for the amnesics and then comparing amnesic recall and normal recall. Amnesic recall was worse than normal recall, despite equated recognition. We conducted two experiments to extend that result. Experiment 1 established that the findings of Hirst et al. are not paradigm specific and hold when amnesic recognition and normal recognition are equated by increasing the retention interval for normals. In Experiment 2 we further established the generality of the result by examining yes-no recognition. Findings further specify the selective nature of the direct memory deficit in amnesics.

Amnesia

Impaired syntactic comprehension and production in Broca's aphasia: CT lesion localization and recovery patterns.

Three of 50 patients with left hemisphere stroke manifested Broca's aphasia associated with deficits in syntactic processing. CT demonstrated anterior infarcts in two patients and a posterior infarct in the third. Two years later, all three patients showed improved syntactic production, but only the patient with the posterior lesion performed significantly above change on a sentence comprehension test requiring syntactic manipulations in the absence of semantic constraints. Prospective investigations combining psycholinguistic analyses and brain imaging techniques may provide empiric data relevant to neurologic models of language and ultimately may contribute to patient prognostication and rehabilitation.

Aged

Retention of reference memory following ischemic hippocampal damage.

Retention of reference memory was evaluated in an animal model of cerebral ischemia. Rats were trained for 70 daily trials on an 8-arm radial maze with 5 arms baited, subjected to 30 minutes of forebrain ischemia, allowed to recover for 30 days, and then tested for an additional 50 trials. Post ischemic (PI) rats demonstrated normal retention of reference memory (p less than 0.05). Working memory was significantly impaired postoperatively (p less than 0.05). Morphologic analysis showed that PI rats had primary loss of pyramidal neurons in the CA1 region of hippocampus.

Animals

Reference and working memory of rats following hippocampal damage induced by transient forebrain ischemia.

Acquisition of reference and working memory was evaluated in an animal model of cerebral ischemia. Rats were subjected to 30 minutes of transient forebrain ischemia, allowed to recover, and then tested for 95 trials on an 8-arm maze with 5 arms baited. During the 95 trials post ischemic (PI) rats made significantly more working and reference errors than controls (p less than 0.05). However, an analysis of the last 20 trials (75-95) showed that while PI rats and control rats had comparable reference memory (p greater than 0.8). PI rats tended to have a persistent working memory deficit compared to controls (p less than 0.06). Subsequent morphologic analysis showed that PI rats had almost complete loss of pyramidal neurons in the anterior CA1 region of the hippocampus, moderate to severe loss in mid-dorsal posterior hippocampus, and less damage to the dorsolateral striatum. These results suggest that the PI animal is a reasonable model for the permanent behavioral impairment and pathologic damage found in some human survivors of cardiac arrest.

Animals

Components of visual attention. Alterations in response pattern to visual stimuli following parietal lobe infarction.

The contribution of attentional factors per se in response to visual stimuli was studied in patients with unilateral lesions of the left or right cerebral hemispheres. Subjects were required to respond to visual targets that were presented tachistoscopically, and were preceded by spatial cues that served to manipulate the spatial locus of attention. On 'valid' cue trials, the cue directed attention to the target's spatial coordinates; on 'invalid' cue trials, the cue misdirected attention. It was determined that damage to either the left or right hemisphere results in a general slowing of reaction times to visual stimuli irrespective of where such stimuli appear, and that patients with right parietal lesions are further impaired at shifting attention within the left visual field.

Adult

Further characterization of patients with amnesia after cardiac arrest: preserved recognition memory.

We observed that patients with amnesia after cardiac arrest had preserved recognition memory despite profound loss of recall memory. In the present study, rate of forgetting was measured in six amnesic subjects for both recall and recognition memory of verbal material. The data show that recall decayed significantly faster for the amnesic subjects than for controls, whereas the rate of forgetting for recognition memory was comparable in both groups. Dissociation between recall and recognition performance is a feature of the amnesic syndrome after cardiac arrest.

Adult