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

Nicaraven is an agent that is especially beneficial in vasospasm or brain damage caused by subarachnoid hemorrhage. It ameliorates neurological deficits of patients and protects the central nervous system from ischemia. We investigated the neuroprotective effect of nicaraven against oxygen-glucose deprivation (OGD) induced or N-methyl-D-aspartic acid (NMDA) induced hippocampal neuronal cell death in organotypic brain slice cultures. The effect of nicaraven on hippocampal neuronal injury was evaluated by inhibition of uptake of propidium iodide (PI) into dead cells. The results demonstrated that nicaraven protected neuronal cells from both OGD- and NMDA-induced cell death. While nicaraven has a strong hydroxyl radical scavenging effect, another radical scavenger, N-acetyl-L-cysteine (NAC), inhibited cell death only caused by OGD. In contrast, the poly(ADP-ribose) synthetase (PARS) inhibitors 3-aminobenzamide (3-AB) and theophylline protected cells from both OGD- and NMDA-induced cell death. Since nicaraven has an inhibitory effect in PARS, as well as a radical scavenging effect, these results suggest that inhibition of hippocampal cell death caused by NMDA may be attributable to PARS inhibition by nicaraven.
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PMID:Possible role of nicaraven in neuroprotective effect on hippocampal slice culture. 1289 15

The aim of this work was to assess effects of a novel asanquineous cardioplegic solution (CP-5), buffered with trisamine (pH 7.6+/-0.1 at 22 degrees C) and containing 21.5 mM aspartic acid and 20.0 mM mannitol, on postischemic functional and metabolic recovery of isolated rat heart. A modified Ringer solution with 25 mM KCl (pH 7.6+/-0.1 at 22 degrees C) and the St. Thomas' cardioplegic solution (pH 7.8+/-0.1 at 22 degrees C) were used as controls. Osmolarity of all cardioplegic solutions were 340+/-5. After 20-min initial perfusion according to Neely (steady state) the hearts were subjected to 40-min normothermal total ischemia followed by 30-min antegrade reperfusion. Cardioplegic solutions were infused prior to ischemia at rate of the initial coronary flow for 5 min at room temperature. During reperfusion the hearts of CP-5 group completely recovered coronary flow and significantly enhanced restoration of the majority functional indices compared to the hearts in both control groups. This effect was combined with less lactate accumulation and preservation of higher ATP and phosphocreatine (PCr) levels in the heart tissue by the end of ischemia and, probably was induced by inclusion of aspartic acid into composition of CP-5. By the end of reperfusion the hearts treated with CP-5 completely recovered PCr content and restored ATP level up to 65.2+/-4.6% of initial one. A better energy state of reperfused hearts in CP-5 group was accompanied by reduction of myocardial lactate tissue to the preischemic value. Restoration of ATP, PCr and lactate content was significantly poor in both control groups during reperfusion. The least formation of a spin adduct of the short life oxygen radicals was found in the myocardial effluent of the hearts of CP-5 group at the early reperfusion using EPR technique. These data suggest a reduced release of oxygen radical generating systems from postischemic myocardium into perfusate due to antioxidant effect of mannitol. The obtained results substantiate addition of aspartic acid and mannitol to the asanquineous cardioplegic solution, buffered with trisamine, to enhance efficacy of myocardial protection against ischemia and reperfusion injury.
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PMID:[Aspartic Acid and mannitol enhance protective efficiency of asanquineous cardioplegic solution]. 1511 77

Ischemic incubation significantly increased amino acid release from rat striatal slices. Reoxygenation (REO) of the ischemic slices, however, enhanced only taurine and citrulline levels in the medium. Ischemia-induced increases in glutamate, taurine and GABA outputs were accompanied with a similar amount of decline in their tissue levels. Tissue final aspartic acid level, however, was doubled by ischemia. Lactate dehydrogenase (LDH) leakage was not altered by ischemia, but enhanced during REO. Presence of tetrodotoxine (TTX) during ischemic period caused significant decline in ischemia-induced glutamate output, but not altered REO-induced LDH leakage. Although omission of extracellular calcium ions from the medium during ischemic period protected the slices against REO-induced LDH leakage, this treatment failed to alter ischemia-induced glutamate and GABA outputs. The release of other amino acids, however, declined 50% in calcium-free medium. Blockade of the glutamate uptake transporter by L-trans-PDC, on the other hand, doubled ischemia induced glutamate and aspartic acid outputs. These results indicate that more than one mechanisms probably support the ischemia-evoked accumulation of glutamate and other amino acids in the extracellular space. Although LDH leakage enhanced during REO, processes involved in this increment were found to be dependent on extracellular calcium ions during ischemia but not REO period.
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PMID:Ischemia and reoxygenation induced amino acid release release and tissue damage in the slices of rat corpus striatum. 1530 72

Alcohol is one of the most common noxious substance to which fetuses are exposed. The aim of the study was to determine the effects of in utero alcohol exposure on excitotoxin-induced neuronal migration disorders. Female hamsters received alcohol (7%) for 3-5 mo or for the last 9-12 d of gestation. Alcohol diet was continued for 5 d during lactation in both groups. Drinking behavior was monitored. Peak plasma alcohol levels were 104+/-12 mg/dL and 225+/-6 mg/dL after 30 min for hamsters receiving an intragastric dose of 3 mL or 5 mL alcohol, respectively. At birth, pups received intrapallial injections ibotenic acid (1 ng, 100 ng, or 10 microg). Histology and N-methyl-D-aspartic acid (NMDA) receptor labeling by 3H-MK-801 in the pups cortices were studied. Short-term-alcohol-exposed pups had normal body and brain weights at birth, but their body growth was retarded postnatally. Ibotenic acid induced similar neuronal migration impairments in control and alcohol-exposed pups (nodular heterotopia in the white matter and/or deep cortical layers, subpial ectopia, and micro- or polymicrogyria). The size of lesions induced by 100 ng ibotenic acid was increased in alcohol-exposed pups; the 10 microg dose was lethal. The density of 3H-MK-801 binding sites was similar in the three groups, indicating that exacerbated ibotenic acid excitotoxicity in alcohol-exposed pups did not result from increased NMDA receptor density. This study shows that alcohol exposure at levels that do not induce neuron migration disorders is sufficient to enhance the effects of the hypoxia-ischemia mimicking effects of ibotenic acid.
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PMID:Effect of perinatal alcohol exposure on ibotenic acid-induced excitotoxic cortical lesions in newborn hamsters. 1558 88

The majority of hippocampal neurons in dissociated cultures and in intact brain exhibit clustering of calcium/calmodulin-dependent protein kinase II (CaMKII) into spherical structures with an average diameter of 110 nm when subjected to conditions that mimic ischemia and excitotoxicity [Neuroscience 106 (2001) 69]. Because clustering of CaMKII would reduce its effective concentration within the neuron, it may represent a cellular strategy to prevent excessive CaMKII-mediated phosphorylation during episodes of Ca2+ overload. Here we employ a relatively mild excitatory stimulus to promote sub-maximal clustering for the purpose of studying the conditions for the formation and disappearance of CaMKII clusters. Treatment with 30 microM N-methyl-D-aspartic acid (NMDA) for 2 min produced CaMKII clustering in approximately 15% of dissociated hippocampal neurons in culture, as observed by pre-embedding immunogold electron microscopy. These CaMKII clusters could be labeled with antibodies specific to the phospho form (Thr286) of CaMKII, suggesting that at least some of the CaMKII molecules in clusters are autophosphorylated. To test whether phosphorylation is involved in the formation and maintenance of CaMKII clusters, the phosphatase inhibitors calyculin A (5 nM) or okadaic acid (1 microM) were included in the incubation medium. With inhibitors more neurons exhibited CaMKII clusters in response to 2 min NMDA treatment. Furthermore, 5 min after the removal of NMDA and Ca2+, CaMKII clusters remained and could still be labeled with the phospho-specific antibody. In contrast, in the absence of phosphatase inhibitors, no clusters were detected 5 min after the removal of NMDA and Ca2+ from the medium. These results suggest that phosphatases type 1 and/or 2A regulate the formation and disappearance of CaMKII clusters.
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PMID:Inhibition of phosphatase activity facilitates the formation and maintenance of NMDA-induced calcium/calmodulin-dependent protein kinase II clusters in hippocampal neurons. 1559 Jan 49

Increased release of glutamate is thought to contribute to ischemia-induced neuronal damage. Since general anesthetics such as thiopental and ketamine are thought to provide some degree of cerebral protection, this study was intended to 1) compare the effectiveness of ketamine and thiopental on ischemia-induced tissue damage; and, if so, 2) determine whether attenuation of the increased amino acid release is the sole mechanism for the protective effects demonstrated. Striatal slices prepared from Wistar Albino rats were incubated in an ischemic medium for 1 hour followed by 5 hours in a reoxygenation (REO) medium. Ketamine and thiopental were added medium during ischemia and/or REO periods, and the medium was collected at the end of each incubation period for measurement of amino acid release and lactate dehydrogenase (LDH) leakage. Ischemia significantly increased amino acid release without altering LDH leakage. Ischemia-induced increments in glutamate and aspartic acid releases returned to control levels during REO, but LDH leakage increased (P > 0.001) during this period. Although ketamine (100 microM) and thiopental (100 microM) failed to decrease ischemia-induced excitatory amino acid release, they protected the slices against REO-induced LDH leakage. Ketamine, but not thiopental, was effective even if added after ischemia (P < 0.05). These results indicate that ketamine and thiopental protect the slices against REO-induced LDH leakage. However, mechanisms other than attenuation of the enhanced glutamate release might be responsible for their protective effects.
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PMID:Effects of ketamine and thiopental on ischemia reoxygenation-induced LDH leakage and amino acid release from rat striatal slices. 1563 38

Transient cerebral ischemia kills CA1 pyramidal cells of the hippocampus, whereas most CA1 interneurons survive. It has been proposed that calcium-binding proteins, neurotrophins, and/or inhibitory neuropeptides protect interneurons from ischemia. However, different synaptic responses early after reperfusion could also underlie the relative vulnerabilities to ischemia of pyramidal cells and interneurons. In this study, we used gramicidin perforated patch recording in ex vivo slices to investigate gamma-aminobutyric acid (GABA) synaptic function in CA1 pyramidal cells and interneurons 4 h after a bilateral carotid occlusion accompanied by hypovolemic hypotension. At this survival time, the amplitudes of both miniature inhibitory postsynaptic currents (mIPSCs) and GABA-evoked currents were reduced in CA1 pyramidal cells, but not in CA1 interneurons. In addition, the mean rise time of mIPSCs was reduced in pyramidal cells. The reversal potential for the GABA current (E(GABA)) did not shift toward depolarizing values in either cell type, indicating that the driving force for chloride was unchanged at this survival time. We conclude that early during reperfusion GABAergic neurotransmission is attenuated exclusively in pyramidal neurons. This is likely explained by reduced GABAA receptor sensitivity or clustering and possibly also reduced GABA release, rather than by an elevation of intracellular chloride. Impaired GABA function may contribute to ischemic neuronal death by enhancing the excitability of CA1 pyramidal cells and facilitating N-methyl-D-aspartic acid channel opening. Therefore, normalizing GABAergic function might be a useful pharmacological approach to counter excessive, and potentially excitotoxic, glutamatergic activity during the postischemic period.
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PMID:Depressed responses to applied and synaptically-released GABA in CA1 pyramidal cells, but not in CA1 interneurons, after transient forebrain ischemia. 1595 57

We investigated the effects of an Na(+)/H(+) exchanger inhibitor, sabiporide, on excitotoxicity in cultured neuronal cells and in vivo. Sabiporide attenuated glutamate- or NMDA (N-methyl-d-aspartic acid)-induced neuronal cell death. Sabiporide also reduced glutamate or NMDA-induced increase in [Ca(2+)](i). In in vivo brain ischemia model, sabiporide produced protective effects, decreasing the infarct size and edema volume. Our results suggest that sabiporide elicits neuroprotective effect both in vitro and in vivo.
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PMID:Effects of sabiporide, a specific Na+/H+ exchanger inhibitor, on neuronal cell death and brain ischemia. 1622 53

The present study examines the hypothesis that aging defined by the 50% survival age compromises neuroprotection afforded by ischemic preconditioning (IPC). Sixty-four male F344 rats aged 4- and 24-months, respectively, were subjected to IPC, (3-min ischemia) or sham-surgery followed by 10-min (full) ischemia or sham-surgery 2 days later. There were 4 groups at each age: sham-surgery-sham-surgery (SS), preconditioning-sham-surgery (PS), preconditioning-ischemia (PI) and sham-surgery-ischemia (SI) groups. Assessments of histology and immunoreactivities of N-methyl-D-aspartic acid receptor 1 (NMDAr1) and caspase-3 active peptide (C3AP) in the hippocampal CA1 region were performed 8 days after full ischemia. The CA1 "living cell ratio" was greater in the aged SI group than in the young SI group (32+/-6% vs. 17+/-5%, p<0.05), whereas the degree of protection against full ischemia afforded by IPC was reduced in the aged compared with the young (53+/-17% vs. 241+/-25%, P<0.0001). The basal level of NMDAr1 immunofluorescence was significantly higher in young animals, while the numbers of C3AP-positive cells were greater in all three aged ischemic groups as compared to respective young groups (p<0.01, p=0.055 and p<0.05). A fourth method of assessing cell damage using Fluoro Jade C labeled degenerating neurons that were also intensively eosinophilic. Counts of Fluoro Jade C-positive cells were higher in the young SI group than in the aged SI group (P<0.05), suggesting that mechanisms of ischemic cell death may change with aging. In conclusion, aging alters mechanisms of ischemic cell death in CA1 neurons and ischemic tolerance mechanisms are blunted by aging.
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PMID:Aging blunts ischemic-preconditioning-induced neuroprotection following transient global ischemia in rats. 1637 18

Metabolic and functional effects of a hypocalcium reperfusion solution (RS) with low oxygen content containing d-glucose, trisamine, d-mannitol and I-aspartic acid have been studied in isolated rat hearts. The hearts were initially perfused for 20 min with the Krebs solution under constant left atrial filling pressure of 15 mm Hg and aortic perfusion pressure of 60 mm Hg. Then they were subjected to 30-min total normothermic ischemia followed by 30-min of reperfusion. The Krebs solution (control, n=16) or RS (n=11) were infused in retrograde mode with a rate of 4 ml/min during first 5 min of reperfusion. After that the hearts of both groups were reperfused in antegrade mode with the Krebs solution for 25 min under initial conditions. Short-term infusion of RS markedly improved postischemic functional recovery of cardiac function. After 30-min reperfusion coronary flow, an index of contractile function intensity, expressed as the left ventricle developed pressure-heart rate product, and cardiac work, calculated as the minute volume-aortic perfusion pressure product, recovered up to 92+/-1%, 77+/-1% and 61+/-1% of baseline values, respectively. In the control group the same indices were significantly lower and were 74+/-3%, 48+/-5% and 33+/-2%, respectively (p<0.001). At the end of reperfusion hearts treated with RS compared with the control hearts showed higher myocardial levels of ATP, phosphocreatine (PCr) and total creatine (SCr). These metabolic findings indicate better recovery of energy state and lesser sarcolemmal damage of postischemic cardiomyocytes after RS infusion. Thus, optimization of administration mode and composition of reperfusion solutions is a promising tool to attenuate functional and metabolic disturbances of the postischemic heart.
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PMID:[Controlled reperfusion improves the metabolic and functional recovery of the isolated heart in rats after total ischemia]. 1671 Jan 99


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