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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apoptosis plays an important role in neuronal cell death in both chronic and acute human neurodegenerative diseases, including amyotrophic lateral sclerosis, Huntington's disease, cerebral ischemia, and human immunodeficiency virus (HIV) encephalopathy. We evaluated the ability of the extracellular binding domain of a dimeric tumor necrosis factor receptor (p75TNFR) to prevent neurotoxicity and death of human fetal cerebral neurons that were exposed in vitro to toxic agents known to be implicated in human neurological disorders, including tumor necrosis factor (TNFalpha) and the HIV proteins Tat and gp120. The extracellular domain of p75TNFR is capable of binding and neutralizing both soluble and transmembrane-anchored TNFalpha. We efficiently transduced human neurons using adenoviral vectors expressing p75TNFR (Ad.p75TNFR) or a control gene (lacZ). Treatment of control cultures with the toxic agents TNFalpha, TNFalpha plus actinomycin D, or Tat and gp120, induced neurotoxic alterations and apoptotic death of neurons. By contrast, transduction of neurons with Ad.p75TNFR prevented apoptosis and cell death due to these agents. We conclude that viral vector transfer of the p75TNFR gene efficiently protects human neurons from TNFalpha-, Tat- or gp120-induced apoptosis and cell death. These results suggest that p75TNFR transduction of neurons by viral vectors could be therapeutically useful in the treatment of many human neurodegenerative diseases.
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PMID:Protection of human cerebral neurons from neurodegenerative insults by gene delivery of soluble tumor necrosis factor p75 receptor. 1582 36

Cerebral vascular diseases, such as neonatal encephalopathy and focal or global cerebral ischemia, all result in reduction of blood flow to the affected regions, and cause hypoxia-ischemia, disorder of energy metabolism, activation of pathogenic cascades, and eventual cell death. Due to a narrow therapeutic window for neuroprotection, few effective therapies are available, and prognosis for patients with these neurological injuries remains poor. Hyperbaric oxygen (HBO) has been used as a primary or adjunctive therapy over the last 50 years with controversial results, both in experimental and clinical studies. In addition, the mechanisms of HBO on neuroprotection remain elusive. Early applications of HBO within a therapeutic window of 3-6h or delayed but repeated administration of HBO can either salvage injured neuronal tissues or promote neurobehavioral functional recovery. This review explores the discrepancies between experimental and clinical observations of HBO, focusing on its therapeutic window in brain injuries, and discusses the potential mechanisms of HBO neuroprotection.
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PMID:Mechanisms of hyperbaric oxygen and neuroprotection in stroke. 1586 72

Proteinases and their inhibitors play important roles in neural development, homeostasis and disease. Neuroserpin is a member of the serine proteinase inhibitor (serpin) superfamily that is secreted from the growth cones of neurons and inhibits the enzyme tissue-type plasminogen activator (tPA). The temporal and spatial pattern of neuroserpin expression suggests a role in synaptogenesis and is most prominent in areas of the brain that participate in learning, memory and behaviour. Neuroserpin also provides neuronal protection in pathologies such as cerebral ischaemia and epilepsy by preventing excessive activity of tPA. Point mutations in neuroserpin cause aberrant conformational transitions and the formation of loop-sheet polymers that are retained within the endoplasmic reticulum of neurons, forming inclusion bodies that underlie an autosomal dominant dementia that we have called familial encephalopathy with neuroserpin inclusion bodies or FENIB. We review here the role of neuroserpin and other proteinase inhibitors in brain development, function and disease.
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PMID:Neuroserpin: a serpin to think about. 1646 51

Rheumatoid arthritis (RA) is a diffuse connective tissue disease and a multi-system disorder with inflammatory process affecting joints in the first place. RA is found in 1 to 3% of population; the first signs of it are usually found in people aged 35 to 50. Neurological pathology in RA is manifested by cervicocranialgia, cervical myelopathy, pathological changes in the upper cervical spine, and cerebral disorders. However, exact mechanisms of the development of central nervous system (CNS) lesions in RA have not been presented. The aim of this study was to clarify the pathophysiological mechanisms and clinical peculiarities of cerebral disturbances in RA. The subjects were 42 female patients, who underwent clinical, neurological, clinicolaboratory, immunological, and clinicophysiological examination. Subjective and objective symptoms were studied; the following syndromes of CNS pathology were distinguished: initial manifestations of cerebral functional insufficiency; disseminated cerebral micro symptoms; focal cerebral lesion. These disorders were accompanied by changes in biochemical parameters which evidenced the presence of connective tissue destruction and immune inflammation. Immunological tests revealed elevation of the level of myelin basic protein antibodies, which correlated with the degree of neurological disturbances and the duration of the disease. The level of myeloperoxidase was elevated, but the degree of this elevation did not depend on the degree of the cerebral disorder and displayed a negative correlation with the duration of the disease. The results of the study demonstrate primary lesion of small vessels in RA--secondary vasculitis followed by demyelinization of CNS white substance. Thus, three forms of cerebrovascular pathology, caused by acute or chronic cerebral vascular insufficiency in RA can be distinguished: initial manifestations of cerebral circulation insufficiency; discirculatory encephalopathy; transient cerebral circulation disturbances and cerebral stroke.
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PMID:[Cerebrovascular disturbances in rheumatoid arthritis]. 1651 96

The results of clinical and biochemical studies of 93 full-term neonatal infants with perinatal hypoxia-induced ischemic nervous system lesion are presented. Perinatal ischemia in the newborns has been found to cause an increase in the serum content of nitric oxide, more significant and stable in severe encephalopathy. The level of nitric oxide remained significantly elevated in the natural development of the disease in children with persistent neurological symptoms; its normalization was observed by the third month of life when the clinical syndromes regressed. The authors proposed to use the blood level of nitric oxide as a marker of acute cerebral ischemia and as an additional criterion for predicting the nervous and mental development of children with prior neonatal ischemia.
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PMID:[The significance of determination of the serum levels of nitrites for assessing severity of perinatal ischemia and predicting the nervous and mental development of a child]. 1675 58

Posterior reversible encephalopathy syndrome (PRES) is a rare neurological condition identifiable by clinical presentation and MRI appearance.1 Patients present with headache, seizures, loss of vision and altered mental function. The pathogenesis of the syndrome is poorly understood. One hypothesis is that cerebral vasospasm results in cerebral ischaemia and subsequent development of T2 hyperintensity, and the other is a temporary failure of the autoregulatory capabilities of the cerebral vessels, leading to hyperperfusion, breakdown of the blood-brain barrier, and consequent vasogenic oedema. It is believed that a rapid rise in blood pressure overcomes cerebral autoregulatory mechanisms with abrupt dilatation of cerebral arterioles. We report a patient with systemic lupus erythematosus and PRES after recurrent spontaneous abortion.
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PMID:Seizures and loss of vision in a patient with systemic lupus erythematosus. 1765 17

In dyscirculatory encephalopathy and moderate ischemic stroke there are single changes of components of glutathione metabolism. In moderate and severe ischemic stroke frequent and considerable changes have been revealed. Changes in hemorrhagic stroke are also expressed. An increase of activities of glutathione peroxidase and glutathione transferase is the most typical, rarely the increase of glutathione reductase and GSH is observed. The increase of enzymes activity was absent at the delayed oneset of treatment (more than 3 days) and in severe cases patients who died later. Glutathione system is important in the tolerance to cerebral ischemia.
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PMID:[Glutathione system in erythrocytes and blood plasma in strokes and dyscirculatory encephalopathy]. 1803 26

The discussion surrounding shaken baby syndrome (SBS) arose from the lack of evidence implicating diffuse axonal injury (DAI) as a cause of death. It was assumed instead that injury to the cervical cord, medulla, and nerve roots played a causal role. The present pathomorphological study examines 18 selected infants (<1-year-old) whose deaths were highly suspicious for SBS, exhibiting the classical SBS triad of acute subdural hemorrhage (SDH), retinal bleeding, and encephalopathy. Gross autopsy and microscopic findings of these infants were compared with those of 19 victims of sudden infant death syndrome (SIDS; control group 1) and of 14 infants who died of disease or injuries/violence not involving the head, neck or eyes (control group 2). Symptoms of mechanical impact to the head were evident in seven of the SBS infants, but in none of the control infants. DAI was not detected in either the SBS or control cases. Localized axonal injury (AI) was regularly present in the brains of the SBS infants surviving longer than 1.5-3.0 h, but only occasionally in the craniocervical junction and within the nerve roots of the upper cervical cord; it was never present in the medulla. Epidural hemorrhage of the cervical cord was seen in four of the ten examined SBS cases, but in none of the control cases. Based on the absence of DAI in the brain and of signs of generalized cervical cord or nerve root injuries, we conclude that the cause of death in the SBS victims was a global cerebral ischemia secondary to SDH, focal vasospasm, trauma-induced transitory respiratory and/or circulatory failure.
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PMID:Shaken baby syndrome: re-examination of diffuse axonal injury as cause of death. 1836 21

Numerous epidemiologic observations reporting high prevalence of migraine among young individuals with stroke as well as dysfunction of cerebral arteries during migraine attacks prompt speculation on the existence of a comorbidity between the two disorders. The recent finding of silent infarct-like brain lesions in migraineurs reinforced this hypothesis and raised questions on whether migraine may be a progressive disorder rather than simply an episodic disorder. Stroke can occur during the course of migraine attacks with aura, supporting the assumption of a causal relation between the two diseases. Migraine may accentuate other existing risk factors for stroke, and both jointly increase the risk of cerebral ischemia outside of migraine attacks. In this regard, the role of migraine might be that of predisposing condition for cerebral ischemia. Migraine and ischemic stroke may be the end phenotype of common pathogenic mechanisms. Evidence of a migraine-stroke relation in cases of specific disorders, such as CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy) and MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes), strongly supports this concept. Finally, acute focal cerebral ischemia can trigger migraine attacks, and, thus, migraine may be the consequence of stroke. In this paper, we will review contemporary epidemiologic studies, discuss potential mechanisms of migraine-induced stroke and comorbid ischemic stroke, and pose new research questions.
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PMID:Migraine and ischemic stroke: a debated question. 1846 Oct 80

Experimental evidence shows that therapeutic hypothermia (TH) protects the brain from cerebral injury in multiple ways. In different models of focal and global cerebral ischemia, mild-to-moderate hypothermia reduces mortality and neuronal injury and improves neurological outcome. In models of experimental intracerebral hemorrhage (ICH), TH reduces edema formation but does not show consistent benefi cial effects on functional outcome parameters. However, the number of studies of hypothermia on ICH is still limited. TH is most effective when applied before or during the ischemic event, and its neuroprotective properties vary according to species, strains and the model of ischemia used. Intrinsic changes in body and brain temperature frequently occur in experimental models of focal and global cerebral ischemia, and may have infl uenced studies on other neuroprotectants. This might be one explanation for the failure of a large amount of translational clinical neuroprotective trials. Hypothermia is the only neuroprotective therapeutic agent for cerebral ischemia that has successfully managed the transfer from bench to bedside, and it is an approved therapy for patients after cardiac arrest and children with hypoxic-ischemic encephalopathy. However, the implementation of hypothermia in the treatment of stroke patients is still far from routine clinical practice. In this article, the authors describe the development of TH in different models of focal and global cerebral ischemia, point out why hypothermia is so efficient in experimental cerebral ischemia, explain why temperature regulation is essential for further neuroprotective studies and discuss why TH for acute ischemic stroke still remains a promising but controversial therapeutic option.
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PMID:Therapeutic hypothermia in experimental models of focal and global cerebral ischemia and intracerebral hemorrhage. 1867 69


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