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

We examined the distribution of synapsin I in the gerbil brain and investigated ischemic damage of presynaptic terminals immunohistochemically by using this protein as a marker protein of synaptic vesicles. The reaction for synapsin I in normal gerbil brain is exclusively localized in the neuropil, and other brain structures such as neuronal soma, dendrites, axon bundles, glia and endothelial cells exhibited little immunoreactivity. In a reproducible gerbil model of unilateral cerebral ischemia, ischemic loss of synapsin I immunoreactivity in the affected hemisphere was confined to the area exhibiting overt infarction, where the breakdown of this protein was also confirmed by the immunoblot analysis, and noted much later than that of microtubule-associated protein 2 immunoreactivity, which was demonstrated in neuronal soma and dendrites. In the non-affected hemisphere, selective damage of presynaptic terminals due to Wallerian degeneration and subsequently occurring resynaptogenesis at the molecular layer of the dentate gyrus were clearly demonstrated as a loss and recovery of immunoreaction for synapsin I, respectively. In a gerbil model of bilateral cerebral ischemia, immunoreaction for synapsin I was persistently preserved after seven days to two months recirculation following a brief period of global forebrain ischemia in the CA1 region of the hippocampus, where delayed neuronal death was consistently observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The synapsin I brain distribution in ischemia. 154 7

Reversible cerebral ischemia (of 5 min, 15 min, or 3-times 5 min) was produced in 14 Mongolian gerbils by occluding both common carotid arteries. After 72 h of recirculation, brains were frozen and processed for measuring regional levels of the polyamines putrescine, spermidine and spermine using HPLC and fluorescent detector. Ischemia induced a marked increase in putrescine levels throughout the brain, most pronounced after 3-times 5 min ischemia (P less than or equal to 0.05 - P less than or equal to 0.001). Spermine levels were significantly reduced, in the hippocampal CA1-subfield after 5 min of ischemia and, in addition, in the striatum and thalamus after 3-times 5 min ischemia. It is suggested that polyamines are released from necrotic neurons and cleared into the blood. Spermine, released from neurons into the extracellular compartment, may bind to the N-methyl-D-aspartate (NMDA) receptor of cells located in close vicinity and may thus render neurons vulnerable to otherwise subtoxic levels of excitotoxins.
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PMID:Changes in regional polyamine profiles in rat brains after transient cerebral ischemia (single versus repetitive ischemia): evidence for release of polyamines from injured neurons. 154 27

In several clinical situations, such as hyposmolar states and hypoxia-ischemia, reductions in the size of the extracellular space are associated with increased seizure susceptibility. Nonsynaptic interactions provide a likely means of mediating the effect of extracellular space on seizure susceptibility. Synchronous bursting of CA1 hippocampal neurons occurs via nonsynaptic mechanisms in solutions containing very low [Ca2+] and excitatory amino acid antagonists. We tested the hypothesis that lowering the osmolality of the extracellular medium could induce nonsynaptic bursting in the dentate gyrus, even though it is normally resistant to this treatment. Extracellular field potentials were recorded in the dentate gyrus and CA1 area of rat hippocampal slices. In the low-[Ca2+] solution with normal osmolality, bursts of population spikes were recorded from the dentate gyrus in only 7% of the slices, but solutions with decreased osmolality induced bursting in 63%. Corresponding values for the CA1 area were 60 and 73%, respectively. Mannitol, which reversed the hyposmolar state, abolished bursting in both regions. This study demonstrates that reducing the size of the extracellular space by lowering extracellular osmolality can transform a seizure-resistant area into one that exhibits robust epileptiform activity.
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PMID:Osmolality and nonsynaptic epileptiform bursts in rat CA1 and dentate gyrus. 154 52

Light microscopic neuronal changes were studied in rats subjected to 10 min of global ischemia produced by compression of the major cardiac vessels. Observations of cresyl violet-stained sections revealed early changes involving predominantly GABAergic neurons in various locations. In rats killed 15 min after recirculation, the changes were characterized by the appearance of a clear peripheral zone with condensation of the remaining neuronal cytoplasm. After 1 h, these zones appeared to be compartmentalized into individual pearl-like vacuoles, especially prominent in the nucleus reticularis thalami. After 3 h, the cytoplasmic vacuoles disappeared and the neuronal changes, particularly in the cerebral cortex, striatum, hippocampus, and pars reticulata of the substantia nigra, consisted mainly of hyperchromasia or loss of Nissl substance. After 2 days, the cerebral cortex and thalamus contained occasional neurons with conspicuously large nucleoli. After 7 days, the hippocampus revealed an approximately 50% loss of CA1 pyramidal neurons, associated with intense microglial reactivity in the stratum radiatum, whereas the neuronal destruction was more complete in the nucleus reticularis thalami. Our observations suggest a possibility that early changes in GABAergic neurons may provide a period of neuronal disinhibition and thus contribute to an excitatory ischemic damage in regions connected by GABAergic circuitry.
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PMID:Global cerebral ischemia associated with cardiac arrest in the rat: I. Dynamics of early neuronal changes. 154 96

The lipid peroxidation inhibitor, U74006F, was tested for neuroprotective properties using the rat four-vessel occlusion model. Adult Wistar rats (136) were randomized to receive pretreatment with either vehicle or U74006F, and exposed to either 15 min (n = 103) or 5 min (n = 33) of transient but severe forebrain ischemia. Surviving criterial animals were reperfused for 72 h, and in the multidose experiments, animals were injected with repeated doses of U74006F or vehicle during the reperfusion period. Vehicle-treated animals exposed to 15 min of ischemia sustained 60 +/- 35% (n = 16) CA1 pyramidal cell necrosis whereas U74006F-treated animals lost 61 +/- 30% (3 mg/kg, n = 9), 42 +/- 35% (10 mg/kg, n = 15), 62 +/- 28% (5 x 10 mg/kg, n = 10), and 74 +/- 30% (8 x 10 mg/kg, n = 10) of CA1 pyramidal cells. No improvement was seen in the injury to cortex or striatum with either pre- or pre- and posttreatment with U74006F. For animals suffering 5 min of transient forebrain ischemia, vehicle-treated rats lost 19 +/- 26% (n = 14), whereas U74006F-treated (8 x 10 mg/kg) animals lost 36 +/- 39% (n = 15) of CA1 neurons. In addition, no protection was discerned in the mildly injured striatum or cortex of these animals. Given the potent effect of U74006F in inhibiting iron-dependent lipid peroxidation in vitro, we question the importance of oxy radicals in the mechanism of postischemic selective neuronal injury in vivo.
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PMID:Failure of the lipid peroxidation inhibitor, U74006F, to prevent postischemic selective neuronal injury. 154 97

Transient arrest of the cerebral blood circulation results in neuronal cell death in selectively vulnerable regions of the rat brain. To elucidate further the involvement of glial cells in this pathology, we have studied the temporal and spatial distribution pattern of activated microglial cells in several regions of the ischemic rat brain. Transient global ischemia was produced in rats by 30 min of a four-vessel occlusion. Survival times were 1, 3, and 7 days after the ischemic injury. The microglial reaction was studied immunocytochemically using several monoclonal antibodies, e.g., against CR3 complement receptor and major histocompatibility complex (MHC) antigens. Two recently produced monoclonal antibodies against rat microglial cells, designated MUC 101 and 102, were also used to identify microglial cells. Following ischemia, the microglial reaction was correlated with the development of neuronal damage. The earliest presence of activated microglial cells was observed in the dorsolateral striatum, the CA1 area, and the dentate hilus of the dorsal hippocampus. However, the microglial reaction was not confined to areas showing selective neuronal damage, but also occurred in regions that are rather resistant to ischemia, such as the CA3 area. Particularly in the frontoparietal cortex, the appearance of MHC class II-positive microglial cells provided an early indication of the subsequent distribution pattern of neuronal damage. The microglial reaction would thus seem to be an early, sensitive, and reliable marker for the occurrence of neuronal damage in ischemia.
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PMID:Immunocytochemical study of an early microglial activation in ischemia. 154 98

We show a differential up-regulation of immunomolecules in the rat dorsal hippocampus accompanying neuronal cell death as a consequence of transient forebrain ischemia (four-vessel occlusion model). Using a panel of monoclonal antibodies (mAbs), we have examined the time course of expression of major histocompatibility complex (MHC) antigens class I (OX-18) and class II (OX-6), leukocyte common antigen (OX-1), CD4 (W3/25) and CD8 (OX-8) antigens, CR3 complement receptor (OX-42), as well as brain macrophage antigen (ED2). The study was performed at time intervals ranging from 1 to 28 days after reperfusion. Throughout all post-ischemic time periods, strongly enhanced immunoreactivity on microglial cells in the CA1 region and dentate hilus and, to a lesser extent, in CA3 was demonstrated with mAb OX-42. MHC class I-positive cells (OX-18) appeared on day 2, whereas cells immunoreactive with OX-1 and W3/25 became evident in the CA1 and hilar regions on post-ischemic day 6. In contrast, MHC class II (Ia) antigen was first detected on indigenous microglia by day 13. In some animals, the OX-8 antibody resulted in the labelling of scattered CD8-positive lymphocytes, but perivascular inflammatory infiltrates were absent. No changes in the expression of ED2 immunoreactivity on perivascular cells could be observed. The results show that following ischemic injury, microglial cells demonstrate a time-dependent up-regulation and de novo expression of certain immunomolecules, indicative of their immunocompetence. The findings are compared with those obtained in other models of brain injury.
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PMID:Progressive expression of immunomolecules on microglial cells in rat dorsal hippocampus following transient forebrain ischemia. 155 47

Synthesis of the polyamines putrescine, spermidine, and spermine is controlled by the activity of the key enzymes ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC). Beside their function in cellular growth processes, polyamines and particularly putrescine play a role in calcium-related events at the cell membrane, coupling an extracellular stimulus to an intracellular response (second messenger-like reactions), modulate the calcium-buffering capacity of mitochondria (spermine), and, if present in the extracellular compartment, modulate the activity of the N-methyl-D-aspartate receptor (spermidine and spermine). Reversible cerebral ischemia triggers pathological disturbances in polyamine metabolism that are characterized by a sharp increase in ODC synthesis, even in the most vulnerable hippocampal CA1 subfield in which overall protein synthesis is severely depressed at the same time, and a marked suppression of SAMDC synthesis in parallel with the inhibition of overall protein synthesis. ODC immunohistochemistry has revealed that the observed changes are neuronal responses to reversible ischemia. These changes in enzyme activities result in an overshoot in the formation of putrescine, the product of ODC activity. Spermine levels are significantly reduced in vulnerable brain structures after prolonged recirculation. In addition, evidence is accumulating that polyamines may be released from the cell during ischemia and after prolonged recirculation at a time when cell necrosis is apparent. This review will summarize the major features of ischemia-induced disturbances in polyamine metabolism and the possible consequences for the cells involved, taking into account that the underlying changes may be indicative of either the activation of a recovery process of neurons from the metabolic stress produced by reversible ischemia or pathological disturbances resulting in the manifestation of neuronal necrosis. Elucidating the mechanisms responsible for the postischemic disturbances in polyamine metabolism may lead to a better understanding of the molecular mechanisms involved in the development of neuronal necrosis after different pathological stimuli.
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PMID:Polyamine metabolism in reversible cerebral ischemia. 156 52

Slice preparations were made from the hippocampus of gerbils after 5 min of ischemia by carotid artery occlusion and the membrane properties of pyramidal neurons were examined. A majority of CA1 neurons lost the capacity for long-term potentiation following tetanic stimulation of the input fibers. CA3 pyramidal neurons, in contrast, preserved responses similar to those in the normal gerbil. Following ischemia, CA1 pyramidal neurons showed increased spontaneous firing that was highly voltage dependent and was blocked by intracellular injection of the Ca2+ chelator, EGTA. Thirty-five percent of CA1 neurons showed an abnormal slow oscillation of the membrane potential after 24 h following ischemia. Intracellular injection of GTP gamma S or IP3 produced facilitation of the oscillations followed by irreversible depolarization. Our results indicate that ischemia-damaged CA1 neurons suffer from abnormal Ca2+ homeostasis, involving IP3-induced liberation of Ca2+ from internal stores.
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PMID:Disturbance of membrane function preceding ischemic delayed neuronal death in the gerbil hippocampus. 156 36

The effect of single or repeated episodes of cerebral ischemia on protein biosynthesis and neuronal injury was studied in halothane-anesthetized gerbils by autoradiography of [14C]leucine incorporation into brain proteins and light microscopy. For quantification of the protein synthesis rate, the steady-state precursor pool distribution space for labeled and unlabeled free leucine was determined by clamping the specific activity of [14C]leucine in plasma, and by measuring free tissue leucine in samples taken from various parts of the brain. Control values of protein synthesis were 14.6 +/- 2.2, 5.8 +/- 2.3, 14.2 +/- 3.1, and 10.0 +/- 3.8 nmol g-1 min-1 (means +/- SD) in the frontal cortex, striatum, CA1 sector, and thalamus, respectively. Following a single episode of 5 or 15 min of ischemia, protein synthesis recovered to normal in all brain regions except the CA1 sector, where it returned to only 50% of control after 6 h and to less than 20% after 3 days of recirculation. After three episodes of 5 min of ischemia spaced at 1 h intervals, protein synthesis remained severely suppressed in all brain regions after both 6 h and 3 days of recirculation. Inhibition of protein synthesis after 6 h predicted histological injury after 3 days of recirculation. In animals submitted to a single episode of 5 or 15 min of ischemia, histological damage was restricted to the CA1 sector but injury occurred throughout the brain after three episodes of 5 min of ischemia. These observations demonstrate that persisting inhibition of protein synthesis following cerebral ischemia is an early manifestation of neuronal injury. Prevention of neuronal injury requires restoration of a normal protein synthesis rate.
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PMID:Neuronal damage after repeated 5 minutes of ischemia in the gerbil is preceded by prolonged impairment of protein metabolism. 156 37


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