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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An intricate interplay between neurotrophic factor and excitatory transmitter signaling systems exists in both the developing and adult brain. Interactions between these signaling systems appears to be a fundamental mechanism regulating adaptive neuritic pruning and cell death. Accordingly, genetically and environmentally induced imbalances in this regulatory system are implicated in the pathogenesis of a variety of acute (such as stroke and traumatic brain injury) and chronic (such as Alzheimer's and Parkinson's diseases) neurodegenerative disorders. Neurons exhibit both acute and delayed responses to neurotrophic factors and excitatory transmitters; acute responses include rapid structural remodeling of growth cones and synaptic contacts, and delayed responses include induction or suppression of the expression of gene products involved in neuroprotection. Intracellular free Ca2+ and free radicals appear to play key roles as mediators of both acute and delayed responses of neurons to excitatory transmitters and neurotrophic factors. For example, the delayed response to bFGF includes stabilization of Ca2+ homeostasis and induction of antioxidant enzymes; both of these actions of bFGF antagonize the dendrite outgrowth-stabilizing and excitotoxic actions of glutamate. Intricate regulatory interactions exist between glutamate and neurotrophic factor signaling systems so that glutamate can induce the expression of neurotrophic factors and their receptors, and neurotrophic factors modulate the expression of exitatory transmitter receptors. A novel signaling system that can interact with both glutamate and neurotrophic factor systems is that of the beta-amyloid precursor protein, which appears to play important roles in neuronal plasticity and survival. A working model for the regulation of neuronal survival and connectivity is presented, which considers spatial and temporal constraints on release of, and receptors for, neurotrophic factors and excitatory transmitters.
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PMID:Calcium and Free Radicals: Mediators of neurotrophic factor and excitatory transmitter-regulated developmental plasticity and cell death. 882 26

Apoptosis is a mode of cell death in which the cell plays an active role in its own death. Apoptosis occurs both within and outside the nervous system. Neural apoptosis occurs not only in neural development, but also in pathophysiological states such as stroke and beta-amyloid peptide toxicity. The mechanism by which apoptosis occurs is unknown, but several genes controlling the process have been identified. In some cases, these genes also have an effect on necrotic neural cell death. The finding that the cell plays an active role in its own death, and that specific gene products are involved, suggests that therapeutic intervention may be feasible.
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PMID:Genetic control of neural cell apoptosis. 882 28

A 53-year-old Japanese woman with a point mutation in mitochondrial DNA (tRNALeu(UUR), nt3243) consistent with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and Alzheimer-type brain pathology is reported. This woman had suffered myopathy and psychosis without any clinical evidence of, stroke-like episodes during the last 10 years of her life, and had died after an accident. At autopsy 30 h post mortem, a part of the brain was snap frozen for biochemical and histochemical studies, and the remaining part was processed for a routine examination and electron microscopy. In the brain there were no ischemic lesions. Instead, primitive/diffuse senile plaques were found throughout the brain, predominantly in the frontal and temporal lobes, while Alzheimer neurofibrillary tangles were found only in the parahippocampal gyrus. These plaques were positive for beta-protein and mostly negative for tau protein, ubiquitin, neurofilaments, alpha-choline acetyltransferase, and acetylcholinesterase. Mutations in codon 331 of the ND2 gene as well as codons 693, 713 and 717 of the beta-amyloid precursor protein gene, known to be responsible for some cases of familial Alzheimer disease, were not found. Furthermore, coincidental Down syndrome was ruled out by chromosome analysis. The results suggest a possible correlation between this mitochondrial DNA abnormality and Alzheimer-type pathology.
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PMID:Alzheimer-type pathology in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). 887 Aug 35

The prevention of dementia is of critical importance. The increasing population of high-risk older individuals will result in an increasing prevalence of dementia. Primary prevention of dementia and Alzheimer disease can take either a public health or high-risk preventive medicine approach. At the present time, there is little evidence to support a specific primary public health approach such as a specific nutrient. The possible association of vascular disease with dementia may offer the best preventive high-risk approach. The identification of individuals with clinical and subclinical vascular disease is possible. There is a very high prevalence of subclinical cerebral infarction in older individuals. Specific treatments can prevent clinical disease such as stroke and coronary heart disease. Whether therapies will prevent some dementia can be determined.
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PMID:Potential prevention of Alzheimer disease and dementia. 887 82

Recent evidence indicates that tumor necrosis factor-alpha (TNF-alpha) is up-regulated following brain injury and in neurodegenerative disorders such as stroke, multiple sclerosis, Parkinson's disease, and Alzheimer's disease. TNF-alpha elicits its biological effects through two distinct TNF receptor (TNFR) subtypes: p55 TNFR (TNFR1) and p75 TNFR (TNFR2). Studies have demonstrated that the p55 TNFR contributes to cell death, whereas the role of the p75 TNFR in neuronal viability is unclear. To better understand the role of p75 TNFR, we treated human neuronal SH-SY5Y cells with phosphorothioate-modified antisense oligonucleotides (ASO) for p75 TNFR and established that ASO inhibited p75 TNFR expression. Treatment of SH-SY5Y cells with ASO alone did not affect cell viability, whereas treatment with both ASO and human TNF-alpha significantly increased cell death relative to treatment with TNF-alpha alone. Moreover, addition of ASO significantly increased the level of cell injury observed following hypoxic conditions or exposure of beta-amyloid peptide. These results indicate that inhibition of p75 TNFR using ASO increases the vulnerability of neurotypic cells to insults and suggest that the p75 TNFR may not be required for normal neuronal cell viability but rather plays a protective role following injury.
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PMID:Inhibition of p75 tumor necrosis factor receptor by antisense oligonucleotides increases hypoxic injury and beta-amyloid toxicity in human neuronal cell line. 901 4

This study determines the early and late survival rates, the causes of death, and prognostic variables that are associated with early and late survival after for ruptured abdominal aortic aneurysm (AAA). These are based on the prospective analysis of 628 variables of data on 158 consecutive patients in 24 centers of our association in 1989. Patients were followed up for a mean of 42.1 +/- 21.0 months. Six patients were lost to follow-up. To identify the variables that were associated with early and late survival, statistical methods included logistic regression analysis, Kaplan-Meier analysis, and Cox regression analysis. The survival rate was 52.9% +/- 14.4% at 1 month, 48.8% +/- 15.8% at 1 year, 48.1% +/- 16.0 at 2 years, 40.3 +/- 19.2% at 3 years, and 35.0 +/- 21.8 at 4 years. The cause of the 73 (46.2%) early deaths were cardiac (33), hemorrhage (29), colonic necrosis (5), stroke (2), graft infection (2), pneumonia (1), and kidney failure (1). Significant predictors of early death were the presence of a common iliac aneurysm (p < 0.02), the age of the patient (p < 0.02), a previous history of stroke or transient ischemic attack (TIA) (p < 0.04), a bifurcated graft (p < 0.04), a saccular aneurysm (p < 0.06), the blood creatinine level (p < 0.06), and hypotension on admission (p < 0.06). The causes of the 28 (17.7%) late deaths were heart disease (11), cancer (8), stroke (3), another operation (3), graft infection (1), pneumonia (1), and Alzheimer disease (1). Significant predictors of late death were heavy smoking (p < 0.03) and chronic obstructive pulmonary disease (p < 0.07). Rupture of an abdominal aortic aneurysm remains a catastrophic event. Even after a successful cure of a ruptured AAA, cardiovascular causes of death are responsible for survival rates that are significantly lower than that in a matched nonaneurysmal population.
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PMID:Surgery for ruptured abdominal aortic aneurysm: early and late results of a prospective study by the AURC in 1989. 906 Nov 46

beta-Amyloid precursor protein (beta APP), transforming growth factor beta (TGF beta), and tumor necrosis factor-alpha (TNF alpha) are remarkably pleiotropic neural cytokines/neurotrophic factors that orchestrate intricate injury-related cellular and molecular interactions. The links between these three factors include: their responses to injury; their interactive effects on astrocytes, microglia and neurons; their ability to induce cytoprotective responses in neurons; and their association with cytopathological alterations in Alzheimer's disease. Astrocytes and microglia each produce and respond to TGF beta and TNF alpha in characteristic ways when the brain is injured. TGF beta, TNF alpha and secreted forms of beta APP (sAPP) can protect neurons against excitotoxic, metabolic and oxidative insults and may thereby serve neuroprotective roles. On the other hand, under certain conditions TNF alpha and the fibrillogenic amyloid beta-peptide (A beta) derivative of beta APP can promote damage of neuronal and glial cells, and may play roles in neurodegenerative disorders. Studies of genetically manipulated mice in which TGF beta, TNF alpha or beta APP ligand or receptor levels are altered suggest important roles for each factor in cellular responses to brain injury and indicate that mediators of neural injury responses also have the potential to enhance amyloidogenesis and/or to interfere with neuroregeneration if expressed at abnormal levels or modified by strategic point mutations. Recent studies have elucidated signal transduction pathways of TGF beta (serine/threonine kinase cascades), TNF alpha (p55 receptor linked to a sphingomyelin-ceramide-NF kappa B pathway), and secreted forms of beta APP (sAPP; receptor guanylate cyclase-cGMP-cGMP-dependent kinase-K+ channel activation). Knowledge of these signaling pathways is revealing novel molecular targets on which to focus neuroprotective therapeutic strategies in disorders ranging from stroke to Alzheimer's disease.
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PMID:Cellular signaling roles of TGF beta, TNF alpha and beta APP in brain injury responses and Alzheimer's disease. 906 86

Recent studies indicate that the proto-oncogene Bax, and other related proteins (eg Bcl-2) may play a major role in determining whether cells will undergo apoptosis under conditions which promote cell death. Increased expression of Bax has been found to promote apoptosis, while over-expression of Bcl-2 can inhibit apoptosis. To investigate the role of Bax in nerve cell death in the rat brain we examined the level of Bax expression in cells undergoing apoptosis, using a hypoxic-ischemic stroke model. We found that Bax was expressed at high levels in the nuclei of neurons in the hippocampus, cortex, cerebellum, and striatum on the control side, and that Bax levels increased in hippocampal neurons undergoing apoptosis on the stroke side, and then declined (correlating with cell loss). In the Alzheimer's disease hippocampi we found a concentrated localisation of Bax in senile plaques, which correlated with the localisation of beta-amyloid protein in adjacent sections from the same brains. beta-Amyloid positive plaques are thought to contribute to the Alzheimer's disease process, possibly via an apoptotic mechanism, and this may occur via an increase in Bax in these areas. Bax was also strongly stained in tau-positive tangles in Alzheimer's disease hippocampi, suggesting Bax may play a role in tangle formation. In addition, we observed a loss of Bax expression in the dentate granule cells of Alzheimer's disease hippocampi compared with moderate Bax expression in control hippocampi, and this loss may be related to the survival of these neurons in Alzheimer's disease. Finally, we observed substantially different staining patterns of Bax using three different commercially available antisera to Bax, indicating the need for caution when interpreting results in this area.
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PMID:Bax expression in mammalian neurons undergoing apoptosis, and in Alzheimer's disease hippocampus. 909 48

Age-dependent neurodegeneration in Alzheimer disease (AD) may be viewed as a complex interaction among: (i) susceptibility polymorphisms, (ii) somatic mutations or alterations that occur over extended periods of time, and (iii) environmental interactions. Putative "sporadic" diseases appear to have a much stronger genetic component than had been considered previously. For example, in Alzheimer disease, apolipoprotein E is a major susceptibility locus that accounts for approximately half the heritability. Specific APOE genotypes are associated with different relative risks and age of onset distributions. Disease may be expressed as a confluence of several genetic risk factors, superimposed upon the age-dependent increments of somatic mitochondrial mutations, and environmental determinants such as head injury, stroke, or hypoxia. A matrix involving each of these complex factors may influence the age of onset of AD in a particular individual. With careful clinically based family and epidemiological studies, it is now possible to tease out the relevant genetic contributions from the confluence of other factors leading to complex disease affecting specific sets of neurons. The highly intricate maze of contributing factors provides many potential unanticipated opportunities to design rational therapeutic and preventative strategies.
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PMID:Apolipoprotein E, a gene with complex biological interactions in the aging brain. 936 Dec 94

Affective disorders are complications of many nervous system diseases. Pathological laughing and crying may accompany cerebrovascular lesions, multiple sclerosis, ALS, Alzheimer disease or cerebral tumours. Precise mechanisms of how these disorders arise are still unknown. Reviews of the literature were been accomplished in the article where, taking the examples of stroke and multiple sclerosis, have been discussed: the clinic picture, pathogenesis in neuroanatomic and neurophysiologic aspects as well as diagnostic criteria and the treatment of uncontrolled pathological laughing and/or crying.
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PMID:[Pathologic laughing and crying in neurologic disorders]. 938 Aug 13


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