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

Seizures are the most frequent neurological event in newborns (NBs), provoked often by noxae not apt to cause them in later life. This is because receptor families of excitatory amino acids (EAA) are overexpressed at this stage of brain ontogenesis, which is also why most neonatal seizures rapidly abate, even when neurological deficits persist. The brain's immaturities dictate distinct seizure phenotypes. A classification proposed in the late 1960s has been criticized, and a new one has been advocated, based on correlations between EEGs and behaviors, leading to a classification of seizures into 'epileptic' and 'non-epileptic'. The taxonomic pitfalls of these classifications are discussed, and the notion advanced that many seizures fail to fulfil the criteria to label them as epileptic. While etiological factors have changed in time, the striking dichotomy in outcome has persisted. Many etiologies, often multifactorial, are unique in NBs, and they are discussed with reference to diagnosis and therapies. Four syndromes of NB seizures, accepted into the International Classification of the Epilepsies, are critically analyzed, some appearing to rest on fragile grounds. Controversies persist whether seizures per se are injurious to the immature brain. Clinical studies suggest that neither duration in days or length of seizure phenotypes correlates with outcomes, the most valid prognostic indices being offered by etiologies and by patterns of EEG polygraphy. However, because most seizures are symptomatic, it may be difficult to distinguish morbidity due to underlying pathology from that possibly added by seizures. Animal experiments suggested that they are injurious. The theory of energy failure, postulated to cause a cascade of events leading to inhibitions of DNA, proteins, lipids and disrupted neuronal proliferation, synaptogenesis, myelination, has largely been disproved. Brains of immature animals have been shown to have the oxidative machinery needed to fulfill energy demands, even during status convulsivus. They are also capable of using anaerobic metabolism and require less ATP when aerobic energy production ceases. Recent explanations for the injurious consequences of hypoxic ischemia and of prolonged convulsions postulate that neuronal damage occurs from excessive release of EAA which, by binding to their ligand-gated ionic receptors, cause a large influx of Ca2+, resulting in cell death. Because of the overabundance of EAA receptors in early ontogenesis, the excitotoxic hypothesis would appear attractive, but some observations militate against it. Among these is the dissociation found between the focal neurotoxicities induced by EAA injected into the brain and their absence following the concomitant convulsions. The latter are not blocked by pretreatment with EAA antagonists, while these prevent injuries caused by the injected EAA. There is no convincing evidence that excessive release of EAA occurs during NBs' seizures. Even if it does occur, it has been shown that immature neurons have a better capacity to self-protect from increased Ca2+ influx, and also that direct application of glutamate to immature neurons leads to significantly lower Ca2+ influx. These data raise doubts about the postulated excitotoxicity caused by NBs' seizures, being consistent with the fact that no one, so far, has observed neuronal damage from drug-induced convulsive states in NBs. Lack of overt neuronal injuries does not preclude that long-term subtle changes might be induced by noxae apt to provoke transient ictal events. Thus models developed in our laboratories demonstrate that long-term epileptogenicity results following postnatal O2 deprivation without evidence of neuronal injuries or of long-term behavioral or electrophysiological alteration. However, both age at which hypoxia occurs and specific proconvulsant methods used strictly determine whether increased epileptogenicity will occur.
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PMID:Neonatal seizures: a clinician's overview. 890 38

The pineal hormone melatonin is neuroprotective in vitro, and in vivo it is neuroprotective when given in pharmacological doses. Consequently, it has been hypothesized that with aging, as circulating levels of melatonin in mammals normally decrease, the brain might be at increased risk of neurodegeneration. However, direct evidence that melatonin deficiency leads to increased brain vulnerability is still lacking. We created melatonin deficiency in rats by pinealectomy and induced neurodegeneration by two models of focal brain ischemia/stroke and by glutamate receptor-mediated, epilepsy-like seizures. We observed greater neurodegeneration in melatonin-deficient animals than in controls. Our results suggest that endogenous melatonin may play a neuroprotective role, and that melatonin deficiency might be a pathophysiological mechanism in neurodegenerative diseases.
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PMID:Increased brain damage after stroke or excitotoxic seizures in melatonin-deficient rats. 894 Mar 1

Increasing evidence indicates that glucocorticoids (GCs), produced in response to physical/emotional stressors, can exacerbate brain damage resulting from cerebral ischemia and severe seizure activity. However, much of the supporting evidence has come from studies employing nonphysiological paradigms in which adrenalectomized rats were compared with those exposed to constant GC concentrations in the upper physiological range. Cerebral ischemia and seizures can induce considerable GC secretion. We now present data from experiments using metyrapone (an 11-beta-hydroxylase inhibitor of GC production), which demonstrate that the GC stress-response worsens subsequent brain damage induced by ischemia and seizures in rats. Three different paradigms of brain injury were employed: middle cerebral artery occlusion (MCAO) model of focal cerebral ischemia; four-vessel occlusion (4VO) model of transient global forebrain ischemia; and kainic acid (KA)-induced (seizure-mediated) excitotoxic damage to hippocampal CA3 and CA1 neurons. Metyrapone (200 mg/kg body wt) was administered systemically in a single i.p. bolus 30 min prior to each insult. In the MCAO model, metyrapone treatment significantly reduced infarct volume and also preserved cells within the infarct. In the 4VO model, neuronal loss in region CA1 of the hippocampus was significantly reduced in rats administered metyrapone. Seizure-induced damage to hippocampal pyramidal neurons (assessed by cell counts and immunochemical analyses of cytoskeletal alterations) was significantly reduced in rats administered metyrapone. Measurement of plasma levels of corticosterone (the species-typical GC of rats) after each insult showed that metyrapone significantly suppressed the injury-induced rise in levels of circulating corticosterone. These findings indicate that endogenous corticosterone contributes to the basal level of brain injury resulting from cerebral ischemia and excitotoxic seizure activity and suggest that drugs that suppress glucocorticoid production may be effective in reducing brain damage in stroke and epilepsy patients.
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PMID:Metyrapone, an inhibitor of glucocorticoid production, reduces brain injury induced by focal and global ischemia and seizures. 896 97

Little is known about the effects of brief potassium depolarization that occurs concurrently with transient ischemia, epilepsy and head trauma. To investigate the effect of short-term depolarization on light (NF-L), middle (NF-M), and heavy (NF-H) neurofilament proteins and determine the role played by calcium in that effect, mixed septo-hippocampal cultures were exposed to 60 mM K+ for 6 min, in the presence of 0 to 11.8 mM Ca2+. Twenty-four hours later, neurofilament immunoreactivity in Western blots of depolarized cultures was decreased to 60% or less of control levels. Decreases were Ca2+-dependent, not due to cell loss, and affected both phosphorylated and nonphosphorylated proteins. The phosphorylation state of NF-M and NF-H influenced the degree of loss observed. Changes in the pattern of immunolabelling of neuritic processes were also associated with depolarization. Thus, brief potassium depolarization may contribute to cytoskeletal disruption following brain injury.
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PMID:Brief potassium depolarization decreases levels of neurofilament proteins in CNS culture. 897 48

Calcium ion (Ca2+) plays a role in several important functions in the central nervous system such as production of action potentials, neurotransmitter release, or neuronal plasticity, etc. However, its excessive influx to neurons due to failure of the mechanisms implicated in the regulation of its intracellular concentration (Ca(2+)-channels, calcium binding proteins), leads to a cascade of events which causes cytotoxicity and neuronal death. Ca2+ mediated toxicity has been implicated in the pathogenesis of neurodegenerative diseases (Parkinson's, Alzheimer's, amyotrophic lateral sclerosis, Huntington's), brain ischemia, epilepsy, cranial trauma, and AIDS-dementia complex. In this article we review the current status of this topic.
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PMID:[Calcium, neuronal death and neurological disease]. 898 15

Hypoxia, ischemia and other forms of brain injury during the pre- and perinatal period may cause neuronal migration disorders which results in irreversible structural modifications. In human neocortex, these malformations have been associated with severe mental retardation, motor dysfunction and the manifestation of therapy-resistant epilepsy. We were interested in analyzing the expression of epileptiform activity in an animal model of neocortical migration disorders. Newborn rats received a focal freeze lesion and were investigated anatomically and in vitro electrophysiologically after survival times of up to five months. Anatomic abnormalities included loss of normal cortical lamination (focal microgyrus) and presence of ectopic cell clusters in layer I and in the white matter (heterotopia). The functional in vitro analyses with eight extracellular recording electrodes revealed a prominent hyperexcitability of the disorganized neocortical network. Electrical stimulation of the afferents elicited epileptiform responses that propagated over > 4 mm in the horizontal direction. In untreated and sham-operated animals, this spread of evoked activity was restricted to 0.5-1 mm. Epileptiform responses were not significantly affected by APV but blocked by NBQX, indicating that AMPA receptors play a prominent role in the generation and propagation of this pathophysiological activity. Our data suggest that the experimentally induced migration disturbances cause long-term structural and/or functional modifications in the neocortical network which may form the basis for the expression of epileptiform activity.
Epilepsy Res 1996 Dec
PMID:Characterization of neuronal migration disorders in neocortical structures: I. Expression of epileptiform activity in an animal model. 898 88

Neuroanatomical methods have been used to study selective vulnerability after global brain ischemia. A consistent pattern of ischemic neuronal damage is found in the rodent hippocampus with loss of CA1 neurons and of some cells in the hilus of the dentate gyrus. Very little is known about plastic changes that would be expected in ischemia-resistant areas such as CA3 neurons and granule cells. Neuronal plasticity after lesions may be indicated by changes in labeling with antibodies to the growth-associated protein 43 (GAP-43). Expression of GAP-43 as a marker for neuronal plasticity was studied here in the hippocampus after global brain ischemia. Halothane-anesthetized rats were subjected to 20 min of transient forebrain ischemia using four-vessel occlusion. In situ hybridization was used to study GAP-43 mRNA at 1, 3, 6, and 12 h and at 1, 3, and 7 days after ischemia. Immunostaining was carried out with two different antibodies to GAP-43 in brains which were perfusion-fixed after 1, 2, 4, and 7/8 days. In the control hippocampus, GAP-43 mRNA was localized to CA1-CA3 and the hilus. Moderate increases in cellular signals were seen in hilar cells and granule cells early after ischemia, and some changes occurred in CA3 at late stages. Hybridization was lost in CA1 due to cell death. With immunostaining, GAP-43 was not seen in the cytoplasm of neurons, whereas dense labeling occurred in a differentiated pattern in the axonal and dendritic layers. At 1 day after ischemia, neurons in the hilus of the dentate gyrus and in the stratum pyramidale and lucidum of CA3 showed strong cytoplasmic labeling for GAP-43. Few cells were labeled in these regions at 2 days, and none at later stages. Pyramidal cells in CA1 and CA3 areas and granule cells were never labeled. These studies demonstrate a transient expression of GAP-43 mRNA and protein in a subset of vulnerable neurons after transient brain ischemia. The cytoplasmic localization in hilar neurons could be due to increased synthesis of GAP-43 or to changes in axoplasmic transport. It is suggested that axonal damage occurs in hilar cells which stimulates GAP-43 expression. The increased production of trophic factors after ischemia in granule cells could also cause plastic changes in hilar cells. Since hilar neurons are in a strategic position to control the excitability of the dentate area, increased expression of GAP-43 may indicate an important pathophysiological process. In seizure experiments, strong expression of GAP-43 mRNA in granule cells was associated with abnormal mossy fiber sprouting and development of chronic epilepsy. The relevance of the minor GAP-43 mRNA upregulation after ischemia must be considered. The changes in CA3 neurons at several days after ischemia might represent a plastic response to a loss of CA1 neurons.
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PMID:Transient expression of GAP-43 within the hippocampus after global brain ischemia in rat. 908 58

Medical issues in sport diving include illnesses that are caused by diving, and medical disorders that compromise safety. Cerebral air embolism and decompression sickness of the brain and spinal cord can result from diving. Sport divers may manifest a spectrum of symptoms from air embolism, which can range from unconsciousness to minimal symptoms, which include fatigue, personality change, poor concentration, irritability, and changes in vision. The physician must search for these minor symptoms in divers who are suspected of pulmonary barotrauma. Medical disorders of concern in diving include diseases of the lungs, the heart, the brain, and the endocrine system, particularly diabetes. Other factors involved in diving safety are exercise capacity and training. Clinical practice standards usually prohibit diving by individuals who have a seizure disorder that requires continuous medication. In the United States, we will not approve diving for individuals who have insulin-dependent diabetes or severe asthma. Some divers can return to diving after myocardial infarction or bypass surgery if they demonstrate good exercise tolerance and no ischemia on a graded exercise test, which simulates the physical activity needed for safe diving.
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PMID:Medical aspects of sport diving. 914 89

Neurodegeneration associated with neurological disorders such as epilepsy, Huntington's Chorea, Alzheimer's disease, and olivoponto cerebellar atrophy or with energy failure such as ischemia, hypoxia, and hypoglycemia proceeds subsequent to overexposure of neurons to excitatory amino acids of which glutamate and aspartate may be quantitatively the most important. The toxic action of glutamate and aspartate is mediated through activation of glutamate receptors of the N-methyl-D-aspartate (NMDA) and non-NMDA subtypes. Antagonists for these receptors can act as neuroprotectants both in in vitro model systems (e.g., cultured neurons) and in vivo. Activation of receptors leads to an increase in the intracellular Ca++ concentration and also to an increase in other second messengers such as cGMP. Thus, Ca++ channel antagonists may have neuroprotective action under certain conditions.
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PMID:Role of Ca+2 and other second messengers in excitatory amino acid receptor mediated neurodegeneration: clinical perspectives. 918 41

Electroencephalographic (EEG) findings in syncope are reviewed. There are four major categories of syncope: neurally mediated (neurocardiogenic), neurologic, decreased cardiac output, and orthostatic hypotension. However, regardless of cause, whether the syncope is due to a vasovagal effect, a cardiac arrhythmia, an epileptic seizure, or hypotension, EEG findings are similar and reflect cerebral hypoperfusion. Initially there may be a slowing of background rhythms. This is followed by high amplitude delta activity, maximal anteriorly. If the hypoperfusion persists there is subsequent flattening of the EEG. The EEG returns to normal in the reverse sequence. In cases with severe and prolonged ischemia, convulsive syncope may occur at the time of the EEG flattening. Although not an epileptic phenomena, clinically this is often mistaken for epilepsy. Conversely, epileptic disorders, such as the ictal bradycardia syndrome, may occasionally mimic syncope. Therefore, in patients in whom EEGs are performed for the evaluation of an episode of loss of consciousness, simultaneous ECG should be used.
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PMID:Electroencephalography in syncope. 924 59


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