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Query: UMLS:C0233794 (memory impairment)
 7,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patient RB became amnesic following an episode of global ischemia that resulted in a bilateral lesion of the CA1 field of the hippocampus. This finding suggested that damage restricted to the hippocampus is sufficient to produce clinically significant memory impairment. To evaluate further the effect of ischemic brain damage on memory, we have developed an animal model of cerebral ischemia in the monkey. Monkeys were subjected to 15 min of reversible ischemia, using a noninvasive technique involving carotid occlusion and pharmacologically induced hypotension. These monkeys sustained significant loss of pyramidal cells in the CA1 and CA2 fields of the hippocampus, as well as loss of somatostatin-immunoreactive cells in the hilar region of the dentate gyrus. Cell loss occurred bilaterally throughout the rostrocaudal extent of the hippocampus but was greater in the caudal portion. Except for patchy loss of cerebellar Purkinje cells, significant damage was not detected in areas outside the hippocampus, including adjacent cortical regions, that is, entorhinal, perirhinal, and parahippocampal cortex, and other regions that have been implicated in memory function. On behavioral tests, the ischemic monkeys exhibited significant and enduring memory impairment. On the delayed nonmatching to sample task, the ischemic monkeys were as impaired as monkeys with lesions of the hippocampal formation and adjacent parahippocampal cortex (the H+ lesion). On two other memory tasks, the ischemic monkeys were less impaired than monkeys with the H+ lesion. In neuropathological evaluations, it has always been difficult to rule out the possibility that significant areas of neuronal dysfunction have gone undetected. The finding that ischemic lesions produced overall less memory impairment than H+ lesions indicates that the ischemic monkeys (and by extension, patient RB) are unlikely to have widespread neuronal dysfunction affecting memory that was undetected by histological examination. These results provide additional evidence that the hippocampus is a focal site of pathological change in cerebral ischemia, and that damage limited to the hippocampus is sufficient to impair memory.
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PMID:Enduring memory impairment in monkeys after ischemic damage to the hippocampus. 161 49

The relationship between changes in learning behavior and neurological damage following transient forebrain ischemia was studied in rats. The transient forebrain ischemia was induced by 4-vessel occlusion, and behavioral experiments were started 4 weeks later when histological damage to the brain seemed to have stabilized. Histological evaluation of brain damage was conducted after completion of the behavioral studies. The rats showed marked learning impairment in a radial maze task done from 4 to 10 weeks after ischemia. In particular, there was an increase in the number of working memory errors according to the duration of forebrain ischemia. However, the same rats showed good avoidance responses in a passive avoidance task done 12 weeks after ischemia. The rats also showed good acquisition of escape response in a water maze task carried out 13 weeks after ischemia, but showed slight impairment of spatial navigation in the transfer test. Marked neuronal degeneration was observed in the hippocampal pyramidal cells of the rats exposed to ischemia. This neuronal damage was closely related to memory impairment in the radial maze task, as demonstrated by a significant negative correlation (r = -0.609 or -0.709) between the number of surviving neurons and the number of reference or working memory errors. These results suggest that rats exposed to transient forebrain ischemia show marked impairment of both reference and working memories as a result of postischemic hippocampal damage.
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PMID:Relationship between brain damage and memory impairment in rats exposed to transient forebrain ischemia. 201 71

Memory is an intellectual function that is initially and consistently impaired in patients with vascular dementia. Experimental approaches to vascular dementia have so far been confined to investigations of memory impairments in rodent ischemic models. Unilateral middle cerebral artery (MCA) occlusion, multiple small embolization or transient four-vessel occlusion in rats produced acute single or multiple infarctions. In such rats, significant memory impairments occurred during the subacute or chronic phases, but were partially reversible. Permanent stenosis of both common carotid arteries in gerbils caused no ischemic changes at 1 day after stenosis but induced multiple infarctions after 1 week of stenosis, probably due either to chronic recurrent ischemia resulting from transient repetitive obstruction of the carotid arteries or to chronic low perfusion. The memory impairments in this model were persistent. Permanent bilateral common carotid artery occlusion in rats produced multiple infarctions plus white matter changes after 1 week of occlusion. Marked memory impairment was also observed in this model. The results of the above studies suggest that memory impairments due to ischemic causes may be partially reversible provided that the infarctions occur only once and are followed by flow recovery. Memory impairments, however, appear to persist if the brain is exposed to chronic recurrent ischemia or chronic moderately low perfusion. A repetitive or persistent low-flow state appears to be an important factor in determining the irreversibility of cognitive impairments.
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PMID:Experimental basis of multi-infarct dementia: memory impairments in rodent models of ischemia. 205 2

Most models of hypoxia and ischemia are used for evaluating the metabolic consequences of cerebral insult. They have also been used for inducing cognitive disturbance. The pathological cascade after severe hypoxia or ischemia includes decreased ATP, influx of Ca2+ and Na+ with decrease in intracellular K+ leading to depolarization, release of glutamate, noradrenaline and acetylcholine, changes in neuronal plasticity, cell death, and cognitive impairment. Possible pharmacological mechanisms for protecting brain function include blockade of Ca2+ influx, inhibition of cell swelling, regulation of membrane potential, inhibition of neurotransmitter release and inhibition of excitatory amino-acid receptors. Among the existing models, many suffer from poor reproducibility and standardization. Two models which are more satisfactory in this respect are global transient ischemia in gerbils induced by bilateral carotid occlusion and focal ischemia in rats induced by occlusion of the middle cerebral artery. Although clear protective effects have been observed in both kinds of model (e.g., with NMDA antagonists, Ca2+ antagonists, PAF antagonists) it is frequently difficult to extrapolate these effects to disorders associated with memory impairment.
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PMID:Models of hypoxia and cerebral ischemia. 218 22

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.
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PMID:Preoperative training modifies radial maze performance in rats with ischemic hippocampal injury. 259 33

Two rat models of memory impairment in passive avoidance learning induced by cerebrovascular disturbance, were established to estimate the effects of a cerebral metabolic enhancer, idebenone. Transient and global cerebral ischemia in rats, produced by 4-vessel occlusion for 200 s immediately after the acquisition trial of passive avoidance learning, shortened the latencies in the retention test trial performed 24 h later. This retrograde amnesia was reversed significantly by idebenone administered orally or intraperitoneally at the doses of 10 and 30 mg/kg before the retention test trial. Idebenone at a dose of 10 mg/kg, given intraperitoneally before or immediately after the ischemia, also markedly inhibited the appearance of amnesia. In the second model, permanent and cerebral hemisphere embolization produced by injecting 2,000 microspheres into the internal carotid artery, significantly impaired passive avoidance learning performed 7 days later. The repeated administration of idebenone (30 mg/kg, i.p.). once a day after the embolization, significantly improved the impairment of passive avoidance learning in the embolized rats. Furthermore, physostigmine and arginine-vasopressin as reference compounds improved the impairment of passive avoidance learning in these models. These findings suggest that idebenone ameliorates memory impairment induced by cerebral vascular disturbance in rats.
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PMID:Effects of idebenone on memory impairment induced in ischemic and embolization models of cerebrovascular disturbance in rats. 276 39

The phenomenon of retrograde amnesia has important implications for understanding normal memory as well as its neural organization. Using 6 tests of remote memory, we evaluated the extent and severity of retrograde amnesia in 2 groups of amnesic patients--7 patients with alcoholic Korsakoff's syndrome and 5 other patients with amnesia (anoxia or ischemia, N = 3; thalamic infarction, N = 1; unknown etiology, N = 1). Although there were individual differences, Experiment 1 showed that the severity and extent of retrograde amnesia was similar for the 2 groups. Retrograde amnesia was temporally graded across a period of about 15 years and was not detectable in more remote time periods. In Experiment 2, repeated testing during a 3 year period showed that amnesic patients and control subjects were similarly consistent in their responses. Amnesic patients did not catch up to control subjects by eventually accumulating as many correct answers as the control subjects. In Experiment 3, amnesic patients performed normally on a test of very difficult general information questions, which were based on material likely to have been learned long ago. In all 3 experiments, the 2 groups of amnesic patients performed similarly. The results support the following conclusions: (1) Extensive, temporally graded retrograde amnesia, which has been observed frequently in patients with Korsakoff's syndrome, occurs readily in other amnesic patients as well, even when their memory impairment appears well circumscribed; (2) patients with presumed damage to either the medial temporal or the diencephalic brain structures linked to memory functions can produce a similar kind of retrograde amnesia; (3) the impairment reflects a loss of usable knowledge, not simply difficulty accessing an intact memory store that can then be overcome given sufficient retrieval opportunities; (4) very remote memory, at least for factual information, can be intact in amnesia; (5) the structures damaged in amnesia support memory storage, retrieval, or both during a lengthy period of reorganization, after which representations in memory can become independent of these structures.
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PMID:The neurology of memory: quantitative assessment of retrograde amnesia in two groups of amnesic patients. 292 83

We investigated the relations of brain edema, ion shifts, motor performance, and memory impairment using a focal ischemia model in rats. Cortical infarction was produced by ligation of the middle cerebral artery and the ipsilateral common carotid artery combined with temporary occlusion of the contralateral common carotid artery for 1 hour. Water content and sodium, potassium, and calcium concentrations were measured until Day 14 after the ischemic insult. Significant edema formation was observed; it peaked on Day 3 (p less than 0.001) and then declined. The tissue sodium concentration changed in a manner similar to that of water content, but the tissue potassium concentration changed in an opposite fashion. Massive accumulation of calcium was detected as early as Day 1 after ischemia (almost four times the normal level). The increased calcium concentration was sustained even up to Day 14. Motor performance examinations performed on Day 3, including inclined plane, balance beam, and prehensile tests, demonstrated significantly reduced (p less than 0.001) motor ability that did recover even by Day 7. Passive avoidance learning was carried out on Day 2, followed by a memory retention test on Day 3. Significant memory dysfunction was observed in ischemic compared with sham-operated rats (p less than 0.001). A high correlation coefficient (r = 0.91, p less than 0.01, n = 13) was obtained between water content and calcium concentration on Day 3. Both the total motor score and the degree of disturbance of the passive avoidance reaction also correlated well with water content.
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PMID:Interrelationship of brain edema, motor deficits, and memory impairment in rats exposed to focal ischemia. 292 28

The goals of this research were to develop a within-subject test of spatial working memory and performance for the rat in a T-maze, based on a delayed alternation, or "win-shift" foraging strategy. Using this model, specific aims were to compare the effects of: (1) age, (2) basal forebrain, medial septal, and amygdala lesions, (3) four vessel occlusion (4-VO), forebrain ischemia, and (4) physostigmine, scopolamine, arecoline, piracetam, and clonidine on memory and performance of young middle-aged, and old rats. Aging significantly impaired working memory and performance of Long-Evans rats. Memory of septal and basal forebrain, but not of amygdala lesioned rats was significantly impaired without effects on performance. Transient, 4-VO forebrain ischemia produced significant memory impairment, without effects on performance, and highly selective CA1 cell loss in the hippocampus. Physostigmine enhanced working memory in middle-aged and old rats. Scopolamine impaired memory in young, middle-aged, and old rats. Physostigmine reversed the scopolamine impairments of working memory. Arecoline enhanced memory in old rats without effects on performance. Piracetam and clonidine had no direct effects on memory, but piracetam increased and clonidine decreased speed of performance. From the aging, lesion, ischemia, and drug studies it was concluded that there was a convergence of evidence from 4 different approaches for a critical role for the hippocampus, particularly the CA1 fields, in spatial working memory.
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PMID:An animal model of human-type memory loss based on aging, lesion, forebrain ischemia, and drug studies with the rat. 306 74

The effect of the psychotropic drug minaprine on brain ischemia induced by a 5-min bilateral occlusion of the carotid arteries in the mongolian gerbil was studied. Severe impairment of memory was apparent when the passive avoidance test was carried out 2 days after the bilaterally induced ischemia. When minaprine in a dose of 50 mg/kg was given p.o. 30 min before the 5-min occlusion, there was a significant improvement in the memory impairment. The amplitude of the hippocampal theta waves decreased and Nissl's degradation was apparent in the CA1 neurons in the hippocampus from 2 days after the 5-min occlusion. Changes in the hippocampal neurons were exacerbated with time. When minaprine in a dose of 50 mg/kg was given there was no decrease in the amplitude of hippocampal theta waves, and Nissl's degradation and the destruction and disappearance of the CA1 neurons diminished considerably. All these findings indicate that minaprine warrants further study for possible clinical prescription.
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PMID:Effect of minaprine on "delayed neuronal death" in mongolian gerbils with occluded common carotid arteries. 361 58


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