Quantitative analysis of peptide and protein changes in ischemic hippocampal tissue by HPLC.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to J M Ordy.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Selective, delayed-onset vulnerability of hippocampal CA1 pyramidal cells has been reported as a unique phenomenon in man and the rat four-vessel occlusion (4-VO) model of global ischemia. This has become of great interest for clarification of CA1 pathophysiology and pharmacological intervention after global ischemia. Studies of pathophysiology and pharmacotherapy appear to be impeded by variability in specific criteria and duration of 4-VO ischemia for producing selective CA1 and differential CA1-CA3 damage. The goals of this study were to: (1) develop specific criteria for 4-VO ischemia to ensure selective, bilaterally symmetrical CA1 pyramidal cell damage, (2) examine the effects of 15 min of ischemia on concomitant CA1 cell necrosis and presence of remaining and/or "viable" neurons postischemia, (3) compare 15 and 30 min of ischemia on differential vulnerability of CA1-CA3 subfields, and (4) evaluate the effects of 15 min of ischemia on CA1 pyramidal cell necrosis and glial fibrillary acidic protein (GFAP)-positive astrocyte reactivity in CA1. After 15 min of ischemia, hippocampal pyramidal cell damage was well delineated, with CA1 severely damaged, but leaving CA3 virtually intact. In contrast, 30 min of ischemia produced severe CA1 and less severe CA3 necrosis. Histological evaluations across Days 1, 3, 6, and 14 indicated a significant delayed onset of CA1-CA3 cell necrosis by Day 3. Counting of remaining cells indicated a detectable loss of some large pyramidal neurons even 1 day after ischemia. Compared to controls, there was a differential increase in GFAP-positive astrocytes in CA1-CA3 after ischemia. The results provided quantitative data on the effects of specific 4-VO criteria and durations on: (1) selective CA1 cell necrosis, (2) differential CA1-CA3 cell vulnerability, (3) presence of postischemic remaining and/or viable neurons, and (4) prospect of a "therapeutic window" for pharmacological treatment of CA1 neuronal injury.
A phosphorylated, approximately 110 kDa laminin-binding protein (110 kDa LBP) from mouse brain has been previously identified. This protein recognizes a neurite-outgrowth promoting 19-amino acid synthetic peptide (PA 22-2) derived from the laminin A chain. In the present study, an antibody against the 110 kDa LBP was used to localize immunoreactivity in the normal adult rat brain and also following a stab wound and ischemic lesion. Immunoreactive cells were found in layers II/III and V of the cerebral cortex and within apical dendrites of pyramidal neurons. Specific immunoreactivity was also found in the stratum lucidum in the CA3 region of the hippocampus which exhibited densely stained mossy fibers and terminals. Mechanical and ischemic lesions induced intense immunolabeling of reactive glial cells around the lesion site. The distinct and anatomically restricted localization of the immunostain in adult and lesioned rat brain suggests that 110 kDa LBP-like molecules might have an important function in forebrain structures and may be involved in the response to CNS injury.
Assessment of cognitive and motor performance of bone marrow transplant patients prior to, during, and following intensive toxic chemoradiotherapy may provide an important adjunct to measures of physiological and medical status. The present study is an attempt to assess whether, as side-effects, these aggressive treatments result in cognitive performance deficits, and if so, whether such changes recover posttreatment. Measurement of cognitive ability in this situation presents special problems not encountered with one-time tests intended for healthy adults. Such tests must be sensitive to changes within a single individual, which emphasizes the crucial importance of high reliability, stability across repeated-measures, and resistance to confounding factors such as motivation and fatigue. The present research makes use of a microbased portable test battery developed to have reliable and sensitive tests which were adapted to study the special requirements of transplant patients who may suffer cognitive deficits as a result of treatment. The results showed slight but significant changes in neuropsychological capacity when compared to baseline levels and controls, particularly near the beginning of treatment. The sensitivity of the battery in detecting such subtle temporary changes is discussed in terms of past research showing effects of other stressors, such as stimulated high altitude and ingestion of alcohol, on these measures.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Studies of human and animal subjects have suggested that exercise may retard aging, help prevent age-related diseases, and prolong life span. Earlier studies focused on the effects of exercise on the heart, skeletal muscles, lungs, metabolism, and longevity. Researchers recently have begun to direct their attention to possible benefits of exercise on the brain. The goals of this study were to examine the effects of voluntary wheel-running exercise on life span, body weight, food and water intake, locomotor performance, and one-trial passive-avoidance memory of mature (10-14 month), middle-aged (20-24 month), and old (28-30 month) C57BL/6J male mice. No significant differences in life span, expressed in months, were found between control and exercised mice when exercise was carried out during maturity, senescence, intermittently across both periods, or continuously throughout maturity and senescence. Exercised adult mice maintained body weight compared to adult controls, an effect not apparent in old mice. Locomotor performance was reduced in old mice, and exercise increased performance much more in adult than in old mice. In the passive avoidance test of recent memory, exercise significantly increased latency, that is, it improved retention, in adult, middle-aged, and old mice. The effect was greatest in middle-aged, next in old, and lowest in adult mice. The findings indicate that exercise may be an important modulator of the rate of aging.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Young (4 to 7 years) and aged (18 to 28 years) rhesus monkeys were sacrificed and various neuromorphometric analyses performed to determine age differences in gross topography, cell population and patterns of cellular degeneration. Two brain regions implicated for their role in age-related cognitive disturbances, the hippocampus and the gyri bordering the principal sulcus in the frontal cortex were selected for these comparisons. Reliable morphometric differences between age groups were observed in both neural areas. One significant difference observed in the hippocampus was a reduced mean depth of the pyramidal layer of the CA-1 zone in the aged monkeys. Also, the mean number of neurons per transverse section in the CA-1 zone of the pyramidal layer was significantly less in the aged monkeys, and in certain instances cell gaps were observed in this region. In the lateral principal gyrus of the frontal cortex, the number of neurons in full-depth "cores" was lower in the old monkeys, glial count was higher and the ratio of neurons to neuroglia, therefore, lower in the older monkeys. Further, the mean area of the principal gyri, measured planimetrically from the apex of the medial gyrus to that of the lateral gyrus was significantly smaller in the aged monkeys. These findings indicate that significant age-dependent cellular differences occur in brain areas thought to be functionally involved in the particular cognitive behaviors most severely impaired in aged monkeys. These differences in brain morphology may, therefore, help provide some leads into the types of neurological changes contributing to the severe cognitive disorders suffered by the elderly.
Five squirrel monkeys were exposed to 200 rads whole-body ionizing irradiation (60Co) at 0.4 rads per second on approximately the seventy-fifth day of gestation, and six squirrel monkeys were sham-irradiated. The mean cortical depth and the mean number of neurons per mm3 in the visual cortex was less in irradiated animals than in controls, but the differences were not statistically significant. The mean number of glial cells in this cortical region was significantly lower in the irradiated animals. An analysis of variance of the combined spine count data from apical, basal, and oblique dendrites revealed a significantly lower number of dendritic spines on basal dendrites in irradiated than in control animals in Meynert neurons in the visual cortex of irradiated offspring. In the hippocampus, the depth of the stratum oriens and the combined depth of the strata radiatum, lacunosum, and moleculare were significantly less in irradiated than in control animals, although the difference in the depth of the pyramidal layer, considered individually, was not statistically significant. The mediolateral width of the CA-1, CA-2, and CA-3 zones, as seen in transverse section, was significantly less in irradiated animals than in controls. The number of dendritic spines per unit length of pyramidal cell dendrite in the CA-1 zone and the total number of pyramidal neurons in the CA-1, Ca-2 and CA-3 zones, per transverse section, were significantly lower in irradiated than in control brains. Canonical correlations provided statistical evidence for greater radiation vulnerability of the hippocampus compared to motor and visual areas of the cerebral cortex.
Because it is of the same taxonomic order as man, the squirrel monkey has been introduced as a nonhuman primate model for the study of such aspects of motion and space sickness as susceptibility, prevention, treatment, and neural mechanisms. In this study on susceptibility, the specific aims were to examine the effects of combined vertical rotation and horizontal acceleration, phenotype, sex, visual cues, morning and afternoon testing, and repeated test exposures on incidence, frequency, and latency of emetic responses. The highest emetic incidence of 89%, with an emetic frequency of 2.0, during 60 min, and a latency of 19 min from onset of testing, occurred at 25 rpm and 0.5 Hz linear acceleration. Susceptibility--defined by incidence, frequency, and/or latency of emesis--was significantly higher in Bolivian than Colombian phenotypes, in the presence of visual cues, in males, but not at different periods of the day or with two successive test exposures. Since the emetic responses were quite similar to man in the eliciting motion stimuli, it was concluded that the squirrel monkey represents a very suitable primate model for studies of motion and space sickness.
The specific aims of this study were to perform direct correlational analyses of age differences in learning, short-term memory and arousal in relation to cell loss and lipofuscin increase in the hippocampus CA1 zone and in visual area 17 of the Fisher 344 rat. The following tentative conclusions can be made from the results presented in this study: (1) significant age differences in 2 and 6 hour passive-avoidance retention or memory between mature and old rats were related to non-significant age differences in days to criterion learning, starting latencies, running distance and time in original approach learning, and (2) significant age differences in 2 and 6 hours retention of old, compared to mature rats were correlated significantly with loss of neurons, and very significantly with increases in intraneuronal lipofuscin in the hippocampus CA1 zone and in visual area 17.
Studies with human and animal subjects have indicated age declines in short-term memory and cell loss in the cortex. Cell loss has been estamated by descriptive nonautomated methods. Declines in short-term memory may be related to reduced learning, movtivation, motor capacity, or some combination of these factors. Passive-avoidance tests of memory minimize these factors. Direct correlational studies on learning and memory in relation to cell loss in the same subject are not feasible in man and they have not been reported previously in animals. The aims of this study were to examine age differences in learning and short-term passive-avoidance memory in relation to cell packing density in the visual cortex of the Fisher 344 rat. Cell counts were made with a computer-guided, automated, image-analyzing system (TAS, Leitz). The following observations were made: (1) significant age differences in 2- and 6-hour short-term passive-avoidance retention or memory between mature and senescent rats were related to nonsignificant age differences in original learning inferred from starting latencies, running time and running distance and (2) sd compared to mature rats were associated with significant differences in neuron but not glia-vascular cell density in area 17 in the presence of nonsignificant age differences in cortical depth and brain weight. Aims of further studies are to establish the role of cell loss from the hippocampus in loss of short-term spatial memory with age and to develop criteria for differential counting of small neurons, glia, endothelial cells and pericytes.
Explore the source record for details and available documents.
Experiments designed to ascertain the effects of oxgen at 8, 10, and 12 psi partial pressure on the brains of pocket mice (Perognathus longimembris) were carried out at room temperature (24 degrees C, 75 degrees F) and at 32 degrees C (93 degrees F). The animals exposed to 8-12 psi at 32 degrees C had been in earlier KO2 oxygen tests. Five animals exposed either to 10 or 12 psi (517 mm or 620 mm HG) PO2 at 32 degrees C died during the course of the tests, possibly as a consequence of injury sustained by the earlier PO2 testing. Autopsy was not carried out. In the other 36 exposed animals, no pathological changes were observed in the brain. It is thus highly probable that oxygen pressures at the hyperbaric levels to which the pocket mice would be exposed during the Apollo XVII mission would not result in any lesions in the brain.