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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

1. The need of the treatment of cognitive impairment due to aging or dementia has led to the search for potential cognition enhancing drugs. The various compounds presently under development represent an alternative to the cholinomimetic therapy and include new chemical entities as well as piracetam and its newer analogs. 2. Recent results from pre-clinical evaluation of the effects on learning on memory are summarized. Emphasis is put on learning and memory experiments under normal and pathological conditions. Most of the nootropics attenuate experimental amnesias induced by scopolamine, cycloheximide, ECS, hemicholinium-3 or forebrain ischemia. These findings suggest that the nootropics may be influencing a common mechanism underlying the amnesias. 3. Biochemical data suggest a potential cholinergic neuronal activity of some of the piracetam analogs. They increase high-affinity choline uptake, and antagonize scopolamine- and ECS-induced decreases in acetylcholine concentrations in the hippocampus. The mode of action of these and all other nootropic compounds, however, is still not known. 4. Despite the interesting results from learning and memory studies and from biochemical investigations, the clinical relevance of these results for amelioration of the cognitive impairment in humans remains to be proven for most of the compounds.
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PMID:Pre-clinical evaluation of cognition enhancing drugs. 269 32

The antiamnesic effects of bifemelane hydrochloride (bifemelane) and indeloxazine hydrochloride (indeloxazine) on radial maze performance in rats were assessed. This performance was dependent on working memory and spatial memory, without aversive electric stimuli. When administered alone, neither bifemelane nor indeloxazine had an effect on the task performance of normal rats. However, impairment of the performance of rats induced by scopolamine hydrobromide (scopolamine) injection was dose-dependently reduced by oral treatment with bifemelane. On the other hand, indeloxazine, which was reported to enhance the learning behavior in a passive avoidance test, did not improve the radial maze task performance of scopolamine-treated rats. It has been shown that dysfunction of the cholinergic neuronal system plays an important role in memory loss and that bifemelane induces recovery of reduced cerebral cholinergic neuronal activity associated with brain ischemia or aging. In accordance with these previous findings, our results suggest that bifemelane is useful in the treatment of memory loss and cognitive dysfunction in patients with dementia and cerebrovascular disease.
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PMID:Comparison of the effects of bifemelane hydrochloride and indeloxazine hydrochloride on scopolamine hydrobromide-induced impairment in radial maze performance. 321 85

In infants who die during the first months of life necrotic foci are almost invariably found. They are, as a rule, located in border zones between vascular territories, suggesting cerebral ischemia as a pathogenetic mechanism. Normally, the brain is protected against changes in perfusion pressure by autoregulation of cerebral perfusion. In utero, this mechanism is extremely fragile, and normal birth is a sufficient hypoxic insult to abolish autoregulation. Abolished autoregulation has been demonstrated in distressed newborns: Even mild hypotension, which is a common occurrence in these infants during the first few hours of life, is sufficient to induce ischemia. Follow-up studies at the ages of one and four years have shown neonatal ischemia to be the decisive factor in the development of atrophic encephalopathy and motor and cognitive dysfunction. This clarification of the pathogenetic process has important implications for prevention, which is briefly discussed.
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PMID:Perinatal cerebral ischaemia and developmental neurologic disorders. 619 41

One of the goals of our laboratory is to examine how the presence of drugs of abuse will influence traumatic brain injury. Previous studies in our laboratory have shown that cocaine or lidocaine treatment before experimental fluid percussion brain injury in rats reduces the cortical hypoperfusion normally found in the early posttraumatic period. The purpose of the current study was to determine if pretreatment with cocaine or lidocaine is also associated with changes in trauma-induced suppression of reflexes and motor and cognitive dysfunction that occurs following traumatic brain injury (TBI). Twenty-four hours after surgical preparation, rats were randomly assigned to a saline or drug pretreatment group, cocaine (0.5, 2, or 5 mg/kg) or lidocaine (2 mg/kg), which was injected via the tail vein. None of the drug pretreatments worsened injury. Lidocaine and cocaine decreased the duration of suppression of some neurological reflexes and reduced posttraumatic body weight losses. Lidocaine and cocaine both decreased postinjury motor deficits. Lidocaine and cocaine did not affect cognitive function on days 11-15 postinjury. The mechanism by which lidocaine improves acute neurological and motor function following brain injury is unknown, but may involve improved posttraumatic cortical blood flow, as seen in our previous study. Our results, along with other studies showing lidocaine to be neuroprotective in animal models of ischemia, suggest that studies of the effect of posttraumatic administration of lidocaine are warranted.
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PMID:The effect of acute cocaine or lidocaine on behavioral function following fluid percussion brain injury in rats. 778 35

In this prospective study, a series of 89 patients with subarachnoid hemorrhage (SAH), most of whom had a "good" neurological outcome, were assessed with a range of tests of memory and cognition as inpatients and at 10 weeks and 12 months after SAH. On tests of verbal cognition and memory, most patients had scores in the normal range 12 months after SAH. However, a significant number of patients still showed impairment on tests of visuospatial construction and memory, mental flexibility, and psychomotor speed at the 12-month assessment. Statistical analyses were carried out for each test score to see whether aneurysm site, location of blood on the admission computed tomographic scan, vasospasm, ischemia, hydrocephalus, grades at admission to and at discharge from hospital, and Glasgow Outcome Scale score at follow-up were associated with test scores. Aneurysm site was not shown to be associated with performance on any test at any time, and the other complications of SAH had only minimal predictive value. The grade at discharge proved to be the best predictor of impairment of cognition and memory at both follow-up assessments. Older subjects did not recover to the same extent as younger subjects by the 12-month assessment. The authors conclude that the diffuse effects of SAH are more important than focal neuropathology in relation to cognitive impairment in this group of patients.
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PMID:A prospective study of impairment of cognition and memory and recovery after subarachnoid hemorrhage. 823 96

Cytidine 5'-diphosphocholine, CDP-choline or citicoline, is an essential intermediate in the biosynthetic pathway of the structural phospholipids of cell membranes, especially in that of phosphatidylcholine. Upon oral or parenteral administration, CDP-choline releases its two principle components, cytidine and choline. When administered orally, it is absorbed almost completely, and its bioavailability is approximately the same as when administered intravenously. Once absorbed, the cytidine and choline disperse widely throughout the organism, cross the blood-brain barrier and reach the central nervous system (CNS), where they are incorporated into the phospholipid fraction of the membrane and microsomes. CDP-choline activates the biosynthesis of structural phospholipids in the neuronal membranes, increases cerebral metabolism and acts on the levels of various neurotransmitters. Thus, it has been experimentally proven that CDP-choline increases noradrenaline and dopamine levels in the CNS. Due to these pharmacological activities, CDP-choline has a neuroprotective effect in situations of hypoxia and ischemia, as well as improved learning and memory performance in animal models of brain aging. Furthermore, it has been demonstrated that CDP-choline restores the activity of mitochondrial ATPase and of membranal Na+/K+ ATPase, inhibits the activation of phospholipase A2 and accelerates the reabsorption of cerebral edema in various experimental models. CDP-choline is a safe drug, as toxicological tests have shown; it has no serious effects on the cholinergic system and it is perfectly tolerated. These pharmacological characteristics, combined with CDP-choline's mechanisms of action, suggest that this drug may be suitable for the treatment of cerebral vascular disease, head trauma of varying severity and cognitive disorders of diverse etiology. In studies carried out on the treatment of patients with head trauma, CDP-choline accelerated the recovery from post-traumatic coma and the recuperation of walking ability, achieved a better final functional result and reduced the hospital stay of these patients, in addition to improving the cognitive and memory disturbances which are observed after a head trauma of lesser severity and which constitute the disorder known as postconcussion syndrome. In the treatment of patients with acute cerebral vascular disease of the ischemic type, CDP-choline accelerated the recovery of consciousness and motor deficit, attaining a better final result and facilitating the rehabilitation of these patients. The other important use for CDP-choline is in the treatment of senile cognitive impairment, which is secondary to degenerative diseases (e.g., Alzheimer's disease) and to chronic cerebral vascular disease. In patients with chronic cerebral ischemia, CDP-choline improves scores on cognitive evaluation scales, while in patients with senile dementia of the Alzheimer's type, it slows the disease's evolution. Beneficial neuroendocrine, neuroimmunomodulatory and neurophysiological effects have been described. CDP-choline has also been shown to be effective as co-therapy for Parkinson's disease. No serious side effects have been found in any of the groups of patients treated with CDP-choline, which demonstrates the safety of the treatment.
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PMID:CDP-choline: pharmacological and clinical review. 870 78

Approximately 15% of all cerebral arteriovenous malformations (AVMs) present with progressive neurologic deficits, the pathogenic mechanism of which has not been established. One suggestion is that AVMs by expanding over time compress normal surrounding cerebral parenchyma and thereby cause progressive neurologic impairment. Alternatively, a vascular steal results in progressive ischemia of normal cerebral tissue. Because the area occupied by the AVM and the area of observed blood flow reductions in all reported patients have overlapped, delineating the relative contribution of local compression from that of vascular steal has not been possible. We present a 7-month-old girl and a 7-year-old boy with AVMs restricted to the diencephalon who had progressive cognitive impairment and dystrophic cerebral hemispheral calcification (in the 7-month-old girl) indicating diffuse cerebral cortical involvement remote from the AVM. These patients provide evidence for vascular steal, and not local compression, as the primary mechanism underlying a progressive neurologic course associated with some AVMs.
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PMID:Progressive neurologic impairment from an arteriovenous malformation vascular steal. 877 Nov 76

The clinical condition known as vascular dementia remains poorly defined. Few studies have attempted a correlative link between the clinical syndrome and the structural abnormalities of the brain. Classically the clinical progression of the vascular dementing process is thought to be a multi-step process punctated by repeated episodes of ischemia, that are clinically expressed as strokes. In most instances it has been assumed that the substrate of vascular dementias consists of atherothrombotic infarcts. The objective of this report is to illustrate 3 cases of progressive (rather than stepwise) cognitive deterioration without clinical evidence of stroke, evolving over a period of several years, in which there were prominent vascular lesions. A complete autopsy and detailed neuropathologic examination demonstrated cerebral vascular lesions involving small arterial vessels (< 200 microns in diameter). The lesions consisted of moderate-to-severe arteriolosclerosis in two cases, and mild-to-moderate arteriolosclerosis in a case of Alzheimer's disease with severe cerebral amyloid angiopathy. Parenchymal lesions consisted of small cortical and subcortical infarcts, most of them smaller than 0.1 cm in average diameter, and subcortical leukoencephalopathy severe in two cases and mild-to-moderate in the third case. Severe atherosclerosis not accompanied by large infarcts was also present in one case. Arterial changes affecting small, distal branches causing sometimes small parenchymal lesions in association with diffuse cerebral white matter disease, appear to be the anatomical substrate that accompanies progressive cognitive impairment in some patients who are frequently diagnosed with Alzheimer's disease because in their clinical records there is neither history of strokes nor stepwise progression of symptoms.
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PMID:Vascular pathology in three cases of progressive cognitive deterioration. 886 69

Cerebrolysin, a peptidergic nootropic drug, was to be effective on learning and other cognitive functions in animal experiments as well as in clinical studies. Hyperventilation (HV) as a model of brain ischemia induces slowing of the EEG and cognitive impairment. The aim of this study was to examine the potential dose-dependent effects of Cerebrolysin on HV related EEG changes and short term memory during chronic (10 days) application and the time dependency of these effects. In this single centre, double blind, randomized, placebo-controlled, parallel group study 48 healthy males were enrolled and received either 100 ml placebo (NaCl) or Cerebrolysin (10 ml or 30 ml or 50 ml) in a volume of 100 ml (NaCl) for 10 days. EEG at baseline and during HV as well as the cognitive performance was evaluated at Day 1 (baseline, 15 min p.i., 2 h p.i., 4 h p.i., 8 h p.i., 24 h p.i.), Day 10 (baseline, 15 min p.i., 2 h p.i.,) and at day 11 (24 h. after the last infusion). The main effects found during the study can be summarized as follows: At baseline we found an increase of the EEG power ratio (PR) for the grouptrated with 10 ml Cerebrolysin. The effect was most pronounced at the parietal cortex. The effect started after 15 min, was most expressed at 2 h and was kept until 8 h. During HV we found a relative PR decrease of the group (10 ml Cerebrolysin) at 2 hours. For short term memory, there is a trend towards less effective word recall for the baseline situation during the first 4 hours for the placebo. This effect was not observed in the Cerebrolysin treated groups. If chronic effects are concerned, the PR increased over the parietal regions at 24 h for the groups treated with 10 and 30 ml Cerebrolysin. The effect remains at day 10 and 11. But at 10 and 11 days there was also a trend for a relative increase of the PR in the group treated with 50ml Cerebrolysin. Signs of overdosage occurred with the highest concentrations of Cerebrolysin. The events were only mild and caused no harm to the volunteers. The highest concentration caused a small but significant reduction of blood pressure. The effects could be interpreted as those of an atypical nootropic with anti-ischemic properties.
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PMID:Dose-dependent effects of Cerebrolysin on EEG and short-term memory of healthy volunteers during control and hyperventilation induced cerebral ischemia. 970 Jun 74


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