Effect of transient cerebral ischaemia on acetylcholine release in the gerbil hippocampus

To clarify the relationship between presynaptic cholinergic dysfunction and postsynaptic cell death in the hippocampus, extracellular levels of acetylcholine (ACh) were assayed and CA1 pyramidal cells were histologically investigated in gerbils which had undergone 2, 5 and 10 min ischaemia. It was found that the KCl- and atropine-induced release of ACh, an index of the functioning cholinergic system at the presynaptic terminals, was significantly lower in the ischaemic groups than in control groups. The hippocampal CA1 pyramidal cell area of the 5 and 10 min ischaemic animals was also significantly decreased, but the 2 min ischaemia caused no cell damage. These findings indicate that the presynaptic terminals of the cholinergic neurone are vulnerable to ischaemic insult and that cholinergic dysfunction precedes postsynaptic CA1 pyramidal cell death in the hippocampus.     

Attributions (beliefs) and job satisfaction associated with back pain in an industrial setting

Transient cerebral ischemia can produce irreversible neuronal damage and permanent learning and memory impairments in humans. This study examined whether ischemia-induced brain damage in rats results in impairments on the delayed nonmatching-to-sample (DNMS) task, a nonspatial recognition task analogous to tests on which amnesic patients display impairments. Male Wistar rats received either sham surgery or 20-min forebrain ischemia induced by bilateral carotid occlusion and hypotension. Four weeks after surgery, ischemic rats were significantly impaired in both learning and performing the DNMS task at retention intervals up to 5 min. Extensive presurgical training did not reduce this impairment. Observable cell loss in ischemic rats was limited to CA1 pyramidal neurons and a subset of cells in the dentate gyrus. The results indicate that ischemic damage to the hippocampus in rats results in recognition memory deficits similar to those produced by ischemic damage in humans.     

Impaired object recognition memory in rats following ischemia-induced damage to the hippocampus.

Transient cerebral ischemia can produce irreversible neuronal damage and permanent learning and memory impairments in humans. This study examined whether ischemia-induced brain damage in rats results in impairments on the delayed nonmatching-to-sample (DNMS) task, a nonspatial recognition task analogous to tests on which amnesic patients display impairments. Male Wistar rats received either sham surgery or 20-min forebrain ischemia induced by bilateral carotid occlusion and hypotension. Four weeks after surgery, ischemic rats were significantly impaired in both learning and performing the DNMS task at retention intervals up to 5 min. Extensive presurgical training did not reduce this impairment. Observable cell loss in ischemic rats was limited to CA1 pyramidal neurons and a subset of cells in the dentate gyrus. Results indicate that ischemic damage to the hippocampus in rats results in recognition memory deficits similar to those produced by ischemic damage in humans. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lack of efficacy of 5-HT2A receptor antagonists to reduce brain damage after 3 minutes of transient global cerebral ischaemia in gerbils

Stimulation of the 5-HT2A receptors by serotonin has been reported to exert an excitatory effect on neocortical neurons in rats and mice, to facilitate ischaemia-induced release of excitatory amino acids and to mediate the vasomotor constrictor component of the response of blood vessels to 5-HT. 5-HT2A receptor antagonists have, therefore, been proposed as potential protectants against the effects of cerebral ischaemia. The aim of this study was to evaluate the effects of two relatively selective 5-HT2A receptor antagonists, ketanserin and ritanserin, on delayed hyperactivity and the ensuing neuronal degeneration induced by 3 minutes of bilateral carotid artery ligation in Mongolian gerbils. Effects were compared to that of flunarizine, which blocks calcium overload and served as a positive control in this paradigm. Temporal and/or rectal temperatures were measured and strictly controlled during the ischaemia and the early reperfusion phase. Locomotor activity was measured one day after the ischaemia and neuronal degeneration quantified 7 days later using an image analysis system (Quantimet 570, Leica). Global ischaemia in gerbils elicits hyperactivity associated with a delayed neuronal degeneration predominantly in the CA1 zone of the hippocampus. Ketanserin and ritanserin (3 and 10 mg/kg ip, twice daily for 3 days, pre- and postischaemia) did not protect the CA1 neurons against ischaemic damage. The postischaemic hyperactivity was inhibited only with the higher dose of ketanserin. As previously reported, flunarizine (30 mg/kg po) markedly reduced neuronal degeneration (-44.2%, p < 0.01) and totally abolished the ischaemia-induced hyperactivity. These data demonstrate that ketanserin and ritanserin are not effective protectants of the gerbil hippocampus against ischaemic damage when the body temperature of the animals is controlled, thus suggesting that 5-HT2A receptors are not directly implicated in the pathogenesis of global cerebral ischaemia in this model.     

Recent results in color compositing of three-parameter magnetic resonance scans as a preoperative aid to the management of upper limb sarcomas

The phenomenon of induced tolerance to a normally lethal episode of ischaemia by preconditioning with sub-lethal ischaemia has been linked to induction of the 72 kDa heat-shock protein (HSP72). However, a direct correlation between HSP72 expression and ischaemic preconditioning in vivo has not been proven. Using an in vitro model of ischaemia-related neuronal damage we have investigated whether HSP72 protein expression is temporally correlated with subsequent tolerance to a normally lethal ischaemic episode. Organotypic hippocampal slice cultures were maintained in vitro for 14 days before being exposed to hypoxia for 15-180 min. Periods of hypoxia shorter than 60 min did not produce neuronal damage. No HSP72 immunoreactivity was observed in either untreated cultures or in those exposed to hypoxia for 15 min. Following 30 and 45 min hypoxia a significant induction of HSP72 occurred in neurons of both the CA1 and CA3/4 regions of the pyramidal cell layer. A significant number of microglia were positively stained with HSP72. The peak of HSP72 expression occurred 18 h after the induction of hypoxia but remained significantly elevated for 48 h post-hypoxia. Prolonged hypoxia (60 or 180 min) produced a selective lesion of the CA1 pyramidal cell layer which was not associated with an induction of HSP72. Pre-conditioning with 45 min hypoxia 18 h prior to 180 min hypoxia did not reduce the neuronal damage associated with 180 min hypoxia alone. These data strongly suggest that HSP72 does not directly confer tolerance in this in vitro model of ischaemia-related neuronal death.     

Mild hypothermia fails to protect late hippocampal neuronal loss following forebrain cerebral ischaemia in rats

Anaesthetized male rats (n = 86) from both Long-Evans strain (LES) (n = 43) and Wistar strain (WS) (n = 43) were utilized for the experiments. While three animals from each strain were used as control, 40 rats from each strain underwent up to 10 minutes forebrain ischaemia by bilateral common carotid artery (CCA) occlusion combined with systemic hypotension [Mean Arterial Blood Pressure (MABP) = 50 mm/Hg]. The animals from each strain were divided into four (n = 10) groups. In both strains, groups (n = 10) 1 and 2, temporalis muscle (TM) and body temperatures of the animals were kept at 36-37 degrees C during the experiments. The groups 1 and 2 were killed in 3 and 7 days after the ischaemic insult, respectively. The groups 3 and 4 were also killed 3 and 7 days after the ischaemic insult, but the forebrain ischaemia was carried out under mild cerebral hypothermia (TM temperature = 33 degrees C). Pyramidal neurons of the hippocampal CA1 region from each group was evaluated semiquantitatively. In WS, groups 1 and 2 showed moderate and severe neuronal loss in the CA1 region, respectively. However, in LES while the group 1 (3 days survival) did not show any neuronal loss, group 2 showed moderate neuronal loss of the CA1 region. While in group 3 (3 days survival, hypothermia) WS and LES, hypothermia protected the CA1 region, group 4 of LES showed mild neuronal loss. However WS, group 4 (7 days survival, hypothermia) showed severe neuronal loss of the CA1 region. It was concluded that mild hypothermia during ischaemic insults did not prevent the delayed postischaemic neuronal damage of the hippocampal CA1 region of both strains, and following 10 minutes forebrain ischaemia, male LES rats were found more resistant than male WS rats to neuronal loss of the CA1 region.     

Inhibition of ischaemic tolerance in the gerbil hippocampus by quercetin and anti-heat shock protein-70 antibody

To clarify the role of heat shock protein-70 (HSP70) in ischaemic tolerance following pretreatment with sublethal cerebral ischaemia, we examined whether the induction of tolerance in the gerbil hippocampus is inhibited by quercetin, an inhibitor of HSP70 expression, or anti-HSP70 antibody. A 3 min period of forebrain ischaemia was induced following pretreatment with 2 min of ischaemia and 3 days of reperfusion. Quercetin or anti-HSP70 antibody was continuously infused into the left lateral ventricle using an implanted osmotic minipump started 3 h after or 2 h before the first ischaemia. The animals were killed 4 days after the second ischaemia for histological observations. Both agents produced no neuronal damage in the brain following a single 2 min period of ischaemia. The neuronal density of the CA1 hippocampus in animals subjected to treatment with quercetin and anti-HSP70 antibody was significantly lower than vehicle-treated animals but were significantly higher than animals with a single 3 min period of ischaemia. Thus, the present study showed that quercetin and anti-HSP70 antibody prevent the induction of ischaemic tolerance. The result suggests that HSP70 expression, at least in part, plays a role in the induction of ischaemic tolerance.     

Alterations in peripheral blood leukocytes functions during enzootic bronchopneumonia of calves. Effect of treatment with antibiotics and immunomodulators

Foetal rat brain aggregation cultures were exposed to a single episode of anoxia and hypoglycaemia for 30 min. Lactate dehydrogenase specific activity was estimated in the culture medium after ischaemia as a marker of lost cell integrity. Release of lactate dehydrogenase was most prominent during the first 24 hr period after the ischaemic damage, then it gradually declined. Immediately after ischaemic exposure, the cultures were treated with different concentrations of L-deprenyl or tolcapone. Significantly lower amounts of lactate dehydrogenase leaked into the culture medium during the first 24 hr after the ischaemic episode in cultures treated with deprenyl or tolcapone (1-100 nM). These results suggest that deprenyl and tolcapone may reduce cell damage after ischaemia, at doses causing enzyme inhibition.     

In vitro and in vivo characterisation of glial cells immortalised with a temperature sensitive SV40 T antigen-containing retrovirus

An oncogene-carrying replication-defective retrovirus was used to establish immortalised lines of murine glial cells. Primary cultures of early postnatal cerebellar cells were infected with a retrovirus based on the Murine Moloney Leukemia Virus containing a temperature-sensitive mutant of the Simian Virus 40 large T antigen (SV40 T) oncogene and a gene coding for resistance to the antibiotic G418. Infected cells were selected in G418 and after several in vitro passages cells expressing the O4 antigen were established as a cell line. At a later time point O4-positive single-cell clones were established. Two different types of clones were obtained: 1) "plastic" clones consisting of cells which initially had a morphological and antigenic phenotype of young glial precursor cells but which gradually lost these features, and 2) "stable" cell clones including a clone with the immunological and electrophysiological characteristics of Schwann cells. Culture of the latter cells in the presence of 1 mM dibutyryl cyclic adenosine monophosphate for a period of at least 10 days induced a change in shape and a shift in antigen expression towards a more "differentiated" maturation stage. When the SV40 T O4-positive immortalised cell line isolated on the cell sorter was transplanted into demyelinated lesions in adult rats, cells were observed ensheathing axons and forming limited amounts of PNS-type myelin. Glial cells immortalised with a temperature-sensitive mutant of the SV40 T oncogene thus retain many physiological properties of their primary culture counterparts and can be induced to undergo limited differentiation in vitro and in vivo. These cell lines, which represent immature CNS glia or Schwann cells, are providing useful tools for investigating the role of cell surface antigens involved in neuron-glial interactions.     

Selective hippocampal lesions and behavior: Effects of kainic acid lesions on performance of place and cue tasks.

Used kainic acid (KA; 1 and 2 μg/μl) lesions to study the effects of damage to the CA3 cell field and subiculum on performance of complex place and cue tasks by 54 male albino rats. In Exp I, neuroanatomical techniques determined the selectivity of the lesions. In a within-Ss design, Ss in Exp II were trained before the operations to run on an 8-arm radial maze with procedures that involved 2 kinds of learning (place and cue) and 2 memory functions (reference memory and working memory). Interrupting the intrahippocampal circuit by damaging the CA3 cell field with KA had minimal effects on performance; injections into subiculum and complete aspiration lesions of hippocampus resulted in impairments on the place but not the cue task. Only intraventricular injections of KA affected performance on both tasks. Results fail to support either the cognitive map or the working memory theory of hippocampal function. It is suggested that distant damage beyond the immediate area of injection complicates interpretation of the results and may limit the usefulness of KA as a neurotoxin in behavioral investigations. (57 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An increase in extracellular glutamate is a sensitive method of detecting ischaemic neuronal damage during cranial base and cerebrovascular surgery. An in vivo microdialysis study

All patients undergoing neurological surgery are at risk for serious complications. Ischaemic damage presenting with hemiparesis or speech difficulties occurs in up to 6% of patients undergoing cerebral bypass procedures and other complicated neurosurgical procedures. Currently available methods for detection of such damage include the use of somatosensory evoked potentials (SSEPs) and electro-encephalography (EEG). Unfortunately, these techniques have false positives and may remain normal in the presence of severe focal neurological deficits. Early detection of potential deficits may prevent or minimize damage through a change in operative or anaesthetic strategy. With the availability of several potential neuroprotective compounds, it is also possible to treat patients at risk of developing ischaemic complications if the individuals are identified early. The excitatory neurotransmitter glutamate is not only a metabolic product, but is also thought to promote ischaemia induced cell injury if released into the extracellular space. It may be a significant parameter for ischaemic brain metabolism. In this report we describe 10 patients who underwent extracranial-intracranial (EC-IC) high flow bypass procedures with routine intra-operative monitoring (IOM) as well as intra-operative in-vivo microdialysis measurement of glutamate. Our aim was to compare intra-operative microdialytic findings and IOM findings with respect to patients' early postoperative clinical courses. Three patients had significant intra-operative glutamate increases indicating ischaemia. Two of these patients awoke with a new neurological deficit (hemiparesis). Routine IOM findings were either normal or showed only transient changes during the time the glutamate levels were high. Our study shows that an increase in extracellular glutamate, as monitored by in-vivo microdialysis, is an excellent early market of neuronal damage. While our glutamate measurements were done off-line, it may be possible to get in future continuous on-line measurements to serve as an early warning system for potential ischaemic damage.     

Selective hippocampal lesions: Differential effects on performance by rats of a spatial task with preoperative versus postoperative training.

102 male Sprague-Dawley rats with selective lesions involving different hippocampal cell fields and/or projections either learned a complex spatial maze postoperatively or were trained preoperatively and tested after the operations. Following damage to anterdorsal CA1 cells and the alveus, acquisition was impaired, but performance was normal when the task was learned preoperatively; postoperative acquisition and performance of the preoperatively learned task were impaired in animals with fimbrial lesions. Data suggest that the CA1 cell field and the projections to the subiculum play an important role in the acquisition of new spatial information but that these connections are not necessary for the utilization of spatial information learned preoperatively. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Development of long-distance efferent projections from fetal hippocampal grafts depends upon pathway specificity and graft location in kainate-lesioned adult hippocampus

Fetal hippocampal cells grafted into the excitotoxically lesioned hippocampus of adult rats are capable of extending axonal projections into the host brain. We hypothesize that the axonal growth of grafted fetal cells into specific host targets, and the establishment of robust long-distance efferent graft projections, require placement of fetal cells in close proximity to appropriate axon guidance pathways. Intracerebroventricular administration of kainic acid in adult rats leads to a specific loss of hippocampal CA3 pyramidal neurons. We grafted 5'-bromodeoxyuridine-labeled embryonic day 19 hippocampal cells into adult hippocampus at four days post-kainic acid lesion, and quantitatively measured the projection of grafted cells into the contralateral hippocampus and the septum after three to four months survival using Fluoro-Gold and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (Dil) tracing. Grafts located in or near the degenerated CA3 cell layer exhibited numerous neurons which established commissural projections with the contralateral hippocampus. However, such projection did not occur in intrahippocampal grafts located away from the CA3 cell layer. In contrast, neurons in all grafts established robust projections into the septum regardless of location within hippocampus although grafts located near the degenerated CA3 cell layer displayed more neurons with such projections. Location of grafted cells clearly influences the development of efferent graft projections into distant targets in the adult host brain, particularly access to axon guidance pathways to facilitate the formation of projections. The establishment of robust long-distance commissural projections of fetal hippocampal grafts is clearly dependent on their placement in or near the degenerated CA3 cell layer, suggesting that appropriate axon guidance pathways for commissural pathways are tightly focussed near this cell layer. However, the establishment of septal projections of these grafts was not dependent on specific location within the CA3 cell layer, suggesting that axonal guidance mechanisms to the septum are more diffuse and not limited to the CA3 dendritic layers. The results underscore that fetal hippocampal grafts are capable of partly restoring lesioned hippocampal circuitry in adult animals when appropriately placed in the host hippocampus.     

Disruption of spatial but not object-recognition memory by neurotoxic lesions of the dorsal hippocampus in rats.

Ischemia-induced cell loss in the CA1 region of the dorsal hippocampus results in severe deficits on delayed non-matching-to-sample (DNMS), whereas hippocampectomy produces little or no impairment, suggesting that partial hippocampal damage is more detrimental to DNMS performance than total ablation. To test this hypothesis, rats with or without preoperative DNMS training were given partial cytotoxic lesions of the dorsal hippocampus. When tested, neither group displayed any DNMS deficits despite widespread cell loss in the CA1 and other regions of the dorsal hippocampus. In the final experiments, rats tested previously on DNMS were found to be impaired on the Morris water maze. The finding that partial hippocampal lesions disrupt spatial memory while leaving object-recognition memory intact indicates a specialized role for the hippocampus in mnemonic processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of CA3 and CA1 in the acquisition of an object-trace-place paired-associate task.

The hippocampus mediates associative learning involving spatial and temporal information. Specifically, paired associations in which a trace interval separates the elements appear to be associated within CA1. In contrast, CA3 appears to be involved in associations containing spatial elements. This suggests that CA3, but not CA1, is involved as long as the spatial association does not contain temporal elements; conversely, CA1 is involved when a temporal element is included, regardless of whether there are spatial elements present. In the present study, rats were run on an object-trace-place paired-associate learning paradigm. Rats with CA3 as well as rats with CA1 lesions showed deficits in the acquisition of this task. These results suggest that CA1 is involved in making arbitrary associations involving a temporal (trace) element, whereas CA3 is involved in making associations that involve spatial elements; furthermore, CA1 and CA3 interact in the presence of both spatial and temporal information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of ibotenate hippocampal and extrahippocampal destruction on delayed-match and -nonmatch-to-sample behavior in rats

The effects of ibotenate lesions of the hippocampus (HIPP) or hippocampus plus collateral damage to extrahippocampal structures (HCX) were investigated in rats trained to criterion on spatial versions of either a delayed-match (DMS) or delayed-nonmatch-to-sample (DNMS) task. After recovery from surgery, animals were retrained at "0" sec delays, then assessed at 0-30 sec delays for 15 d, retrained again at 0 sec delays, and retested for another 25 d on 0-30 sec delays. Pretrained HIPP-lesioned animals showed marked delay-dependent deficits in both tasks that never recovered. Detailed examination of within- and between-trial performance factors, including changes in response preferences, length of previous trial delay, and sequential dependencies, revealed important factors operating in lesioned animals that were either absent or insignificant before the lesion. Pretrained HCX-lesioned animals showed deficits similar to those of HIPP animals, with the noticeable exception of a strong "recency" influence of the previous trial. Another group of HIPP- and HCX-lesioned animals trained on the tasks after the lesion showed reduced impairments of the type described above, suggesting that extrahippocampal structures trained after the lesion can assume the role of the hippocampus to some degree. The findings indicate that both the type of lesion and the previous history of the animal determine the postlesion DMS and DNMS performance of animals suffering damage to the hippocampus and/or related structures.     

Ischemia-induced object-recognition deficits in rats are attenuated by hippocampal ablation before or soon after ischemia.

The literature on the role of the hippocampus in object-recognition contains a paradox: Transient forebrain ischemia (ISC) produces hippocampal damage and severe deficits on the delayed nonmatching-to-sample (DNMS) task, yet hippocampal ablation (ABL) produces milder deficits. Experiment 1 confirmed that pretrained rats display severe DNMS deficits following ISC, but not ABL. Ischemia produced loss of CA1 neurons. but no obvious extrahippocampal damage. In Experiments 2 and 3, ISC rats from Experiment 1 received ABL. and ABL rats received ISC: neither treatment affected DNMS performance. In Experiment 4, rats that received ISC followed 1 hr later by ABL displayed only mild deficits. It is hypothesized that ISC-induced DNMS deficits are due to extrahippocampal damage produced by pathogenic processes that involve the hippocampus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Metabolic disarrangement in ischemic heart disease and its therapeutic control

The term myocardial ischaemia describes a condition which exists when fractional uptake of oxygen in the heart is not sufficient to maintain the rate of cellular oxidation. This leads to extremely complex situations which have been extensively studied in recent years. A large amount of experimental research has been directed to establish the precise sequence of biochemical events leading to myocyte necrosis as such knowledge could lead to rational treatments designed to delay myocardial cell death. At the present time there is no simple answer to the question of what determines cell death and no recovery on reperfusion. Problems arise because: (1) ischaemic damage is not homogeneous and many factors may combine to cause cell death; (2) severity of biochemical changes and development of necrosis are usually associated (both processes being dependent on the duration of the ischaemia) and it is impossible to establish a causal relationship; (3) the inevitability of necrosis can only be assessed by reperfusion of the ischaemic myocardium. Restoration of flow, however, might result in numerous further negative consequences, thus directly influencing the degree of recovery. From the clinical point of view, I have recently learned that there are several potential manifestations and outcomes associated with myocardial ischaemia and reperfusion. Without doubt ventricular dysfunction (either systolic or diastolic) of the ischaemic zone is the most reliable clinical sign of ischaemia, since ECG changes and symptoms are often absent. The ischaemia-induced ventricular dysfunction, at least initially, is reversible, as early reperfusion of the myocardium results in restoration of normal metabolism and contraction. In the ischaemic zone, recovery of contraction might occur instantaneously or, more frequently, with a considerable delay, thus yielding the condition recently recognized as the stunned myocardium. On the other hand, when ischaemia is severe and prolonged, cell death might occur. Reperfusion at this stage is associated with the release of intracellular enzymes, disruption of cell membranes, influx of calcium, persistent reduction of contractility, and eventual necrosis of at least a portion of the tissue. This entity has been called reperfusion damage by those who believe that much of the injury is the consequence of events occurring at the moment of reperfusion rather than as result of changes occurring during the period of ischaemia. The existence of reperfusion damage, however, has been questioned, and it has been argued that, with the exception of the induction of arrhythmias, it is difficult to be certain that reperfusion causes further injury. The existence of such an entity has clinical relevance, as it would imply the possibility of improving recovery with specific interventions applied at the time of reperfusion. In 1985 Rahimtoola described another possible out-come of myocardial ischaemia. He demonstrated that late reperfusion (after months or even years) of an ischaemic area showing ventricular wall-motion abnormalities might restore normal metabolism and function. He was the first to introduce the term hibernating myocardium, referring to ischaemic myocardium in which the myocytes remain viable but in which contraction is chronically depressed. Our data on metabolic changes occurring during ischaemia followed by reperfusion obtained either in the isolated and perfused rabbit hearts or in CAD patients undergoing intracoronary thrombolysis or aortocoronary by-pass grafting will be reviewed.     

Spreading depression determines acute cellular damage in the hippocampal slice during oxygen/glucose deprivation

During ischaemia neurons depolarize and release the neurotransmitter L-glutamate, which accumulates extracellularly and binds to postsynaptic receptors. This initiates a sequence of events thought to culminate in immediate and delayed neuronal death. However, there is growing evidence that during ischaemia the development of spreading depression (SD) can be an important determinant of the degree and extent of ischaemic damage. In contrast, SD without metabolic compromise (as occurs in migraine aura) causes no discernible damage to brain tissue. SD is a profound depolarization of neurons and glia that propagates like a wave across brain tissue. Brain cell swelling, an early event of both the excitotoxic process and of SD, can be assessed by imaging associated intrinsic optical signals (IOSs). We demonstrate here that IOS imaging clearly demarcates the ignition site and migration of SD across the submerged hippocampal slice of the rat. If SD is induced by elevating [K+]O, the tissue fully recovers, but in slices that are metabolically compromised at 37.5 degrees C by oxygen/glucose deprivation (OGD) or by ouabain exposure, cellular damage develops only where SD has propagated. Specifically, the evoked CA1 field potential is permanently lost, the cell bodies of involved neurons swell and their dendritic regions increase in opacity. In contrast to OGD, bath application of L-glutamate (6-10 mM) at 37.5 degrees C evokes a non-propagating LT increase in CA1 that reverses without obvious cellular damage. Moreover, application of 2-20 mM glutamate or various glutamate agonists fail to evoke SD in the submerged hippocampal slice. We propose that SD and OGD together (but not alone) constitute a 'one-two punch', causing acute neuronal death in the slice that is not replicated by elevated glutamate. These findings support the proposal that SD generation during stroke promotes and extends acute ischaemic damage.     

Working memory in aged rats.

The performances of young and aged rats were compared on a spatial (spatial delayed nonmatching-to-sample) and a nonspatial (object delayed nonmatching-to-sample) test of working memory. Although evidence was found that aging slowed acquisition of both of these tasks, performance over different retention intervals of up to 60 sec was normal once the task was mastered. An impairment was found, however, in the performance of the spatial test when the number of locations to be remembered on each trial was increased from one to two. The conclusions of this study are that under some conditions, the retention capabilities of aged rats may not change and that some acquisition impairments do not reflect alterations in learning or memory per se, but, in common with other studies, deficits in the remembrance of spatial locations may be found. (PsycINFO Database Record (c) 2010 APA, all rights reserved)