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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

An emerging concept in neurobiology is that the adult brain retains a capacity for plasticity and functional reorganization throughout the life span. Experimental data from electrophysiological, morphological and behavioral studies have documented experience dependent plasticity in the intact and injured adult brain. Neuroimaging clinical studies indicate altered post stroke functional activation patterns, usually including activation of the intact hemisphere. However, there is some disagreement regarding their functional significance and longitudinal studies correlating outcome and activation pattern are needed to solve some controversies. Postoperative housing of rats in activity stimulating environment after ligation of the middle cerebral artery significantly enhances outcome. Gene expression for brain derived neurotrophic factor and Ca2+/calmodulin-dependent protein kinase II, two substances with potential role in brain plasticity, show different patterns in animals housed in standard and in enriched environment. The functional significance of altered gene expression needs to be evaluated.
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PMID:Environmental influence on gene expression and recovery from cerebral ischemia. 1049 41

Previous studies have shown that several different neurotrophic factors can prevent death of cortical and hippocampal neurons induced by excitotoxic and oxidative insults in cell culture and in vivo. Because neuronal degeneration may be initiated by alterations occurring in synaptic compartments in disorders ranging from Alzheimer's disease to stroke, we tested the hypothesis that neurotrophic factors can exert direct protective actions at the level of the synapse. We now report that a nine amino acid bioactive fragment of activity-dependent neurotrophic factor (ADNF-9) enhances basal glucose and glutamate transport, and attenuates oxidative impairment of glucose and glutamate transport induced by amyloid beta-peptide and Fe(2+), in neocortical synaptosomes. Preservation of transporter function required only short-term (1-2 h) pretreatments. Basic fibroblast growth factor (bFGF) was also effective in suppressing oxidative impairment of synaptic transporter functions, while nerve growth factor (NGF) was less effective. Additional analyses showed that ADNF-9, bFGF and NGF suppress oxidative stress and mitochondrial dysfunction induced by amyloid beta-peptide and Fe(2+) in synaptosomes. Our data suggest that ADNF-9 can act locally in synaptic compartments to suppress oxidative stress and preserve function of glucose and glutamate transporters. Such synapto-protective actions suggest roles for activity-dependent trophic signaling in preventing degeneration of neuronal circuits, and indicate possible therapeutic applications of agents that stimulate local synaptic (transcription-independent) neurotrophic factor signaling pathways.
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PMID:Neurotrophic factors protect cortical synaptic terminals against amyloid and oxidative stress-induced impairment of glucose transport, glutamate transport and mitochondrial function. 1063 95

The neuroprotective potential of halothane anesthesia was investigated following unilateral electrolytic lesions to the forelimb representation area of the sensorimotor cortex (FL-SMC). Previously, it was found that the FL-SMC lesion increases substantially in size when the intact forelimb is immobilized with a plaster of paris cast for the first 7 days postlesion, which forces extreme overuse of the impaired forelimb during a time when nonlethally damaged tissue is vulnerable to behavioral demand. Initially, the purpose of this study was to investigate whether intracisternal infusion of basic fibroblast growth factor (bFGF or FGF-2), a potent neurotrophic factor that has been shown to have neuroprotective and plasticity promoting properties in focal stroke and other injury models, could prevent this use-dependent exaggeration of injury. Although intracisternal bFGF (starting 24 h after surgery, twice per week) was not found to produce significant neuroprotective or behavioral effects, the brief exposure to halothane anesthesia (15-20 min) during bFGF or vehicle administration was found to prevent expansion of the lesion size, and to reduce delayed loss of neurons in the substantia nigra pars reticulata (SNr). The data have implications for investigations of the effects of neurotrophic factor in vivo, and other investigations requiring brief, intermittent halothane anesthesia.
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PMID:Focal brain injury, FGF-2 and the adverse effects of excessive motor demand on cortical and nigral degeneration: marked protection by delayed intermittent exposure to halothane. 1110 Dec 9

It is remarkable that neurons are able to survive and function for a century or more in many persons that age successfully. A better understanding of the molecular signaling mechanisms that permit such cell survival and synaptic plasticity may therefore lead to the development of new preventative and therapeutic strategies for age-related neurodegenerative disorders. We all know that overeating and lack of exercise are risk factors for many different age-related diseases including cardiovascular disease, diabetes and cancers. Our recent studies have shown that dietary restriction (reduced calorie intake) can increase the resistance of neurons in the brain to dysfunction and death in experimental models of Alzheimer's disease, Parkinson's disease, Huntington's disease and stroke. The mechanism underlying the beneficial effects of dietary restriction involves stimulation of the expression of 'stress proteins' and neurotrophic factors. The neurotrophic factors induced by dietary restriction may protect neurons by inducing the production of proteins that suppress oxyradical production, stabilize cellular calcium homeostasis and inhibit apoptotic biochemical cascades. Interestingly, dietary restriction also increases numbers of newly-generated neural cells in the adult brain suggesting that this dietary manipulation can increase the brain's capacity for plasticity and self-repair. Work in other laboratories suggests that physical and intellectual activity can similarly increase neurotrophic factor production and neurogenesis. Collectively, the available data suggest the that dietary restriction, and physical and mental activity, may reduce both the incidence and severity of neurodegenerative disorders in humans. A better understanding of the cellular and molecular mechanisms underlying these effects of diet and behavior on the brain is also leading to novel therapeutic agents that mimick the beneficial effects of dietary restriction and exercise.
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PMID:Neuroprotective signaling and the aging brain: take away my food and let me run. 1111 86

An accumulating body of evidence clearly establishes that estradiol is a potent neuroprotective and neurotrophic factor in the adult: it influences memory and cognition, decreases the risk and delays the onset of neurological diseases such as Alzheimer's disease, and attenuates the extent of cell death that results from brain injuries such as cerebrovascular stroke and neurotrauma. Thus, estradiol appears to act at two levels: 1) it decreases the risk of disease or injury; and/or 2) it decreases the extent of injury incurred by suppressing the neurotoxic stimulus itself or increasing the resilience of the brain to a given injury. During the past century, the average life span of women has increased dramatically, whereas the time of the menopause has remained essentially constant. Thus, more women will live a larger fraction of their lives in a postmenopausal, hypoestrogenic state than ever before. Clearly, it is critical for us understand the circumstances under which estradiol exerts protective actions and the cellular and molecular mechanisms that underlie these novel, nonreproductive actions.
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PMID:Minireview: neuroprotective effects of estrogen-new insights into mechanisms of action. 1118 7

Although cerebral hypoperfusion caused by cerebral occlusive disease leads to cerebral ischemic events, an effective treatment has not yet been established. Recently, a novel therapeutic strategy for ischemic disease using angiogenic growth factors to expedite and/or augment collateral artery development has been proposed. Therapeutic angiogenesis might be useful for the treatment of cerebral occlusive disease. Hepatocyte growth factor (HGF) is a potent angiogenic factor, in addition to vascular endothelial growth factor (VEGF), whereas in the nervous system HGF also acts as neurotrophic factor. Therefore, we hypothesized that gene transfer of these angiogenic growth factors could induce angiogenesis, thus providing an effective therapy for cerebral hypoperfusion or stroke. In this study, we employed a highly efficient gene transfer method, the viral envelop (Hemagglutinating Virus of Japan [HVJ]-liposome) method, because we previously documented that beta-galactosidase gene could be transfected into the brain by the HVJ-liposome method. Indeed, we confirmed wide distribution of transgene expression using beta-galactosidase via injection into the subarachnoid space. Of importance, transfection of HGF or VEGF gene into the subarachnoid space 7 days before occlusion induced angiogenesis on the brain surface as assessed by alkaline phosphatase staining (P<0.01). In addition, significant improvement of cerebral blood flow (CBF) was observed by laser Doppler imaging (LDI) 7 days after occlusion (P<0.01). Unexpectedly, transfection of HGF or VEGF gene into the subarachnoid space immediately after occlusion of the bilateral carotid arteries also induced angiogenesis on the brain surface and had a significant protective effect on the impairment of CBF by carotid occlusion (P<0.01). Interestingly, coinjection of recombinant HGF with HGF gene transfer revealed a further increase in CBF (P<0.01). Here, we demonstrated successful therapeutic angiogenesis using HGF or VEGF gene transfer into the subarachnoid space to improve cerebral hypoperfusion, thus providing a new therapeutic strategy for cerebral ischemic disease.
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PMID:Gene transfer of hepatocyte growth factor to subarachnoid space in cerebral hypoperfusion model. 1201 87

Fetal rat kidney cells produce high levels of glial-derived neurotrophic factor (GDNF) and exert neuroprotective effects when transplanted into the brain in animal models of Parkinson's disease and stroke. The purpose of the present experiment was to produce kidney cell lines that secrete GDNF. Genes encoding two truncated N-terminal fragments of SV40 large T antigen, T155g and T155c, which does not code for small t antigen, were used. T155g was transduced into E17 cultured fetal Sprague-Dawley rat kidney cortex cells using a plasmid vector, and T155c was transduced with a plasmid and a retroviral vector. Sixteen clones were isolated from cultures transfected with the T155g-expressing plasmid. No cell lines were obtained with T155c. Four clones produced GDNF at physiological concentrations ranging from 55 to 93 pg/ml of medium. These four clones were transplanted into the ischemic core or penumbra of rats that had undergone middle cerebral artery occlusion (MCAO). Three of the four clones reduced the volume of infarction and the behavioral abnormalities normally resulting from MCAO. Blocking experiments with antibodies to GDNF and platelet-derived growth factor (PDGF) suggested that these growth factors contributed only minimally to the reduction in infarct volume and behavioral abnormality. These cell lines may be useful for intracerebral transplantation in animal models of brain injury, stroke, or Parkinson's disease.
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PMID:T155g-immortalized kidney cells produce growth factors and reduce sequelae of cerebral ischemia. 1207 90

The possible neuroprotective effect of physical exercise was investigated in rats after middle cerebral artery occlusion (MCAO), a focal stroke model. It was found that physical exercise in the form of a 12-week treadmill running programme reduced the volume of infarction caused by MCAO. At the molecular level, reverse transcription polymerase chain reaction revealed that the runner had increased gene expression for nerve growth factor (NGF) over the nonrunner with or without MCAO. Expression of the NGF receptors, p75, was increased only in the absence of MCAO. In addition, runners showed a significantly higher number of cholinergic neurons, which constitutively expressed p75, in the horizontal diagonal band of Broca. The present findings suggest that neuroprotection after physical exercise may be a result of an increase in an endogenous neurotrophic factor nerve growth factor and the proliferation of its receptive cholinergic neurons.
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PMID:Neuroprotection associated with running: is it a result of increased endogenous neurotrophic factors? 1269 70

Sendai virus (SeV) vector-mediated gene delivery of glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) prevented the delayed neuronal death induced by transient global ischemia in gerbils, even when the vector was administered several hours after ischemia. Intraventricular administration of SeV vector directed high-level expression of the vector-encoded neurotrophic factor genes, which are potent candidates for the treatment of neurodegenerative diseases. After occlusion of the bilateral carotid arteries of gerbils, SeV vector carrying GDNF (SeV/GDNF), NGF (SeV/NGF), brain-derived neurotrophic factor (SeV/BDNF), insulin-like growth factor-1 (SeV/IGF-1) or vascular endothelial growth factor (SeV/VEGF) was injected into the lateral ventricle. Administration of SeV/GDNF, SeV/NGF or SeV/BDNF 30 min after the ischemic insult effectively prevented the delayed neuronal death of the hippocampal CA1 pyramidal neurons. Furthermore, the administration of SeV/GDNF or SeV/NGF as late as 4 or 6 h after the ischemic insult also prevented the death of these neurons. These results indicate that SeV vector-mediated gene transfer of neurotrophic factors has high therapeutic potency for preventing the delayed neuronal death induced by transient global ischemia, and provides an approach for gene therapy of stroke.
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PMID:Postischemic administration of Sendai virus vector carrying neurotrophic factor genes prevents delayed neuronal death in gerbils. 1496 Oct 67


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