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

Natural polyamines, putrescine, spermidine and spermine, exhibit a number of neurophysiological and metabolic effects in brain preparations. In the in vitro studies, several specific sites of action have been identified such as ion channels, transmitter release and Ca2+ homeostasis. Polyamines have been linked to the development of neuronal degeneration caused by, for instance, epileptic seizures and stroke. The role of endogenous polyamines in the functioning brain is not clear, however. We review the work carried out using state-of-the-art transgenic animal models for polyamine research. A number of transgenic mouse lines carrying human ornithine decarboxylase, spermidine synthase and S-adenosylmethionine decarboxylase gene have been generated. Of these animals those with ornithine decarboxylase transgene show an extensive and constitutive expression of the enzyme in the brain with an exceedingly high putrescine concentration, a phenotype that is not encountered under physiological conditions. In this article we review the neurometabolic, behavioural and histological data that has been obtained from these transgenic mice.
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PMID:Transgenic animals as models in the study of the neurobiological role of polyamines. 878 35

We used in situ hybridization to localize the long-term changes in ornithine decarboxylase (ODC) expression after a 90 min occlusion of the middle cerebral artery (MCAO) in the rat. The ODC mRNA was induced in the ipsilateral dentate gyrus (DG) and throughout the ischemic cortex at 12 h and still at 3 days after reperfusion. The induction was blocked by an N-methyl-D-aspartate (NMDA) receptor antagonist suggesting that ODC induction is NMDA receptor-mediated. The long-lasting up-regulation detected in regions where no cellular damage usually occurs, favors the hypothesis that ODC expression does not contribute to neuronal death after stroke.
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PMID:Induction of ornithine decarboxylase mRNA in transient focal cerebral ischemia in the rat. 946 58

Nuclear magnetic resonance imaging (MRI) was used to study dynamics of maturation and the size of ischaemic stroke lesions in rats with greatly increased activity of ornithine decarboxylase (ODC). Syngenic rats, either with or without chronic pre-ischaemic treatment with an ODC inhibitor, alpha-difluoromethylornithine (DFMO), as well as ODC-overexpressing transgenic rats were subjected either to transient middle cerebral artery (MCA) occlusion or permanent occlusion of the cortical branch of MCA. The two models were chosen to assess the role of ODC activity in damage caused by ischaemia and reperfusion, respectively. Diffusion of water was quantified by means of the trace of the diffusion tensor (D(av) = 1/3 Trace D) to assess the extent of energy failure and cytotoxic oedema, whereas the spin-spin relaxation time (T2) was used as a quantitative indicator of irreversible damage by MRI. Exposure to transient MCA occlusion resulted in significantly smaller stroke lesions in the ODC-overexpressing transgenic (246+/-14 mm3) than in syngenic (320+/-9 mm3) or DFMO-treated (442+/-63 mm3) rats as determined 48 h after the occlusion. The differences in sizes were due to smaller lesions in the cortical tissue (transgenic vs. syngenic) or both in cortical and striatal regions (transgenic vs. DFMO-treated animals). The degree of irreversible oedema was greater in DFMO-treated rats than in syngenic or transgenic animals indicating accelerated development of a permanent damage in the absence of ODC induction. Cortical infarct following permanent MCA occlusion developed faster in the DFMO-treated than in syngenic or transgenic rats as the lesion sizes at 10 h were 26.2+/-4.3 mm3, 14.2+/-2.3 mm3 and 12.3+/-1.9 mm3, respectively. However, the stroke volumes by 48 h were not statistically different in the three animal groups. The present data demonstrate that ODC activation is an endogenous neuroprotective measure in transient cerebral ischaemia.
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PMID:Neuroprotective role of ornithine decarboxylase activation in transient focal cerebral ischaemia: a study using ornithine decarboxylase-overexpressing transgenic rats. 975 92

Natural polyamines, spermidine and spermine, and their precursor putrescine, are of considerable importance for the developing and mature nervous system. They exhibit a number of neurophysiological and metabolic effects in the nervous system, including control of nucleic acid and protein synthesis, modulation of ionic channels and calcium-dependent transmitter release. The polyamine system is also known to be involved in various brain pathologic events (seizures, stroke, Alzheimer's disease and others). While cerebral polyamine concentrations and the activities of polyamine-metabolizing enzymes have been studied in great detail, much less is known about the cells that are responsible for cerebral polyamine synthesis and interconversion. With the present review the attempt is made to show how exact knowledge about the regional distribution and cellular localization of polyamines and the polyamine-synthesizing enzymatic machinery (and especially of L-ornithine decarboxylase) may help to better understand the functional interplay between polyamines and other endogenous agents (transmitters, receptors, growth factors neuroactive drugs etc.). Polyamines have been localized both in neurones and glial cells. However, the main cellular locus of the ODC is the neuron--both in the immature and adult central nervous system. Each period of normal brain development and ageing seems to have its own, characteristic temporo-spatial pattern of neuronal ODC expression. During strong functional activation (kindling, epileptic seizures, neural transplantation) astrocytes and other non-neuronal cells do also express ODC and other polyamine-metabolizing enzymes. Astroglial expression of ODC is accompanied by an increase in glial fibrillary acidic protein in these cells. This shift in the cellular mechanisms of polyamine metabolism is currently far from being understood. In human brain diseases (Alzheimer's disease, schizophrenia) certain neurones show an increased expression of ODC, the first and rate-limiting enzyme of polyamine metabolism. Since polyamines are structurally related to psychoactive drugs (neuroleptics, antidepressants) the polyamine system might be of importance as a putative target for drug intervention in psychiatry.
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PMID:The cellular localization of the L-ornithine decarboxylase/polyamine system in normal and diseased central nervous systems. 1021 98

The polyamines, putrescine, spermidine and spermine are present in most living cells, with the essentiality for normal cell function, cellular growth and differentiation. In the mammalian brain, polyamines are also present at relatively high concentrations with different regional distribution profiles. Cerebral ischemia is a leading cause of disability and mortality in humans, and believed to yield a cascade of cytotoxic molecules responsible for the death of viable cells in the brain. Polyamines have been implicated in the pathogenesis of ischemic brain damage. For example, polyamine biosynthesis is increased after the onset of cerebral ischemia through an induction of ornithine decarboxylase, a key enzyme in the polyamine biosynthetic pathway. The administration of a drug that inhibits ornithine decarboxylase activity prevents the development of ischemic brain damage, suggesting a critical role of the accumulation of polyamines in the ischemic brain in the pathogenesis of stroke. Both spermine and spermidine are linked to the development of glutamate-mediated neurotoxicity, for they can bind to the N-methyl-D-aspartate (NMDA)-sensitive subtype of glutamate receptors to potentiate cellular responses to glutamate. Moreover, polyamines are metabolized by polyamine oxidases after acetylation to produce different cytotoxic aldehydes and reactive oxygen species such as hydrogen peroxide, which possibly damage proteins, DNA and lipids. Polyamines have been extensively studied in the ischemic brain, particularly with respect to neuronal responses such as NMDA receptor-mediated excitotoxicity. However, little is known about glial responses to polyamines in the ischemic brain to date. In this review, we would summarize previous studies related to neuronal and glial responses to polyamines in the ischemic brain.
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PMID:Neuronal and glial responses to polyamines in the ischemic brain. 1618 Nov 15

Polyamines are small cationic molecules that in adult brain are connected to neuronal signaling by regulating inward-rectifier K(+)-channels and different glutamate receptors. Antizyme inhibitors (AZINs) regulate the cellular uptake of polyamines and activate ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine synthesis. Elevated levels of ODC activity and polyamines are detected in various brain disorders including stroke and Alzheimer's disease (AD). We originally reported a novel brain- and testis-specific AZIN, called AZIN2, the distribution of which we have now studied in normal and diseased human brain by in situ hybridization and immunohistochemistry. We found the highest accumulation of AZIN2 in a pearl-on-the-string-like distribution along the axons in both the white and gray matter. AZIN2 was also detected in a vesicle-like distribution in the somas of selected cortical pyramidal neurons. Double-immunofluorescence staining revealed co-localization of AZIN2 and N-methyl D-aspartate-type glutamate receptors (NMDARs) in pyramidal neurons of the cortex. Moreover, we found accumulation of AZIN2 in brains affected by AD, but not by other neurodegenerative disorders (CADASIL or Lewy body disease). ODC activity is mostly linked to cell proliferation, whereas its regulation by AZIN2 in post-mitotically differentiated neurons of the brain apparently serves different purposes. The subcellular distribution of AZIN2 suggests a role in vesicular trafficking.
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PMID:Brain neurons express ornithine decarboxylase-activating antizyme inhibitor 2 with accumulation in Alzheimer's disease. 1983 40


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