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

Neurons from cerebral cortex and hippocampal CA1 sector exhibit a striking difference in vulnerability to transient ischemia. To establish whether this difference is due to the inherent (pathoclitic) properties of these neurons, the ischemic susceptibility was studied in primary cortical and hippocampal cultures by using a new model of argon-induced in vitro ischemia. Neuronal cultures were exposed at 37 degrees C for 10-30 min to argon-equilibrated glucose-free medium. During argon equilibration, Po2 declined to < 2.5 torr within 1 min and stabilized shortly later at approximately 1.3 torr. After 30 min of in vitro ischemia, total adenylate was < 45% and ATP content < 15% of control in both types of culture. Cytosolic calcium activity increased from 15 to 50 nM. Reoxygenation of cultures after in vitro ischemia led to delayed neuronal death, the severity of which depended on the duration of in vitro ischemia but not on the type of neuronal cultures. Energy charge of adenylate transiently returned to approximately 90% of control after 3 h, but ATP content recovered only to 40% and protein synthesis to < 35%. Cytosolic calcium activity continued to rise after ischemia and reached values of approximately 500 nM after 3 h. The new argon-induced in vitro ischemia model offers major advantages over previous methods, but despite this improvement it was not possible to replicate the differences in cortical and hippocampal vulnerability observed in vivo. Our study does not support the hypothesis that selective vulnerability is due to an inherent pathoclitic hypersensitivity.
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PMID:Susceptibility of hippocampal and cortical neurons to argon-mediated in vitro ischemia. 885 46

MR imaging has firmly established its place as the cornerstone of pediatric neuroimaging. Recent advances in MR imaging have led to decreased imaging time, high resolution studies, and new methods for obtaining tissue contrast. Magnetic resonance angiography (MRA) now obviates the need for angiography in some children, although its extended role is still to be defined. Normal and abnormal development and myelination patterns have been further defined with MR imaging. The patterns of brain injury resulting from hypoxia and ischemia vary with the degree of the insult as well as the gestational age of the child. These patterns of hypoxic-ischemic encephalopathy can be analyzed to determine when the insult occurred. Neuronal migration disorders and phakomatoses can be diagnosed with confidence at an early age, thus facilitating genetic counseling. MR imaging can detect the most common lesions associated with childhood epilepsy, such as hippocampal sclerosis, focal cortical dysplasias, and low-grade tumors. Other areas, including pediatric AIDS, toxicity-related injury, metabolic/mitochondrial conditions, and disorders associated with iatrogenic injury, can be diagnosed with MR. Spectroscopy provides information that should prove useful in evaluating and monitoring neuronal and other brain tissue disorders in children.
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PMID:MR of the brain in children. 887 Jan 79

1. Electrophysiological changes of CA1 pyramidal neurons in rat hippocampus were studied before, during 5 min forebrain ischemia, and after reperfusion using in vivo intracellular recording and staining techniques. 2. membrane input resistance of CA1 neurons decreased from 25.98 +/- 7.24 M omega (mean +/- SD, n = 42) before ischemia to 16.33 +/- 6.50 M omega shortly after the onset of ischemia (n = 6, P < 0.01). The input resistance fell to zero during ischemic depolarization and quickly returned to 24.42 +/- 10.36 M omega (n = 11) within 2 h after reperfusion. 3. The time constant of CA1 neurons decreased from 11.49 +/- 5.45 ms (n = 36) to 3.09 +/- 1.66 ms (n = 6, P < 0.01) during ischemia. The time constant remained significantly less than preischemic levels within 2 h after reperfusion (5.40 +/- 2.60 ms, n = 13, P < 0.01) and gradually returned to preischemic levels 4-5 h after reperfusion. 4. The spike height decreased from 91 +/- 10.35 mV (n = 45) before ischemia to 82 +/- 8.00 mV (n = 9, P < 0.05) within 2 h after reperfusion and fully returned to preischemic level 2-5 h after reperfusion. The spike width increased from 1.14 +/- 0.22 ms (n = 45) before ischemia to 1.36 +/- 0.22 ms (n = 9, P < 0.05) within 2 h after reperfusion and remained at this level 4-5 h after reperfusion. 5. The spike threshold significantly increased from -54 +/- 3.93 mV (n = 45) before ischemia to -49 +/- 5.04 mV (n = 8, P < 0.01) within 2 h after reperfusion. The rheobase increased accordingly from 0.34 +/- 0.16 nA (n = 41) to 0.73 +/- 0.26 nA (n = 6, P < 0.01). The spike threshold returned to control levels 4-5 h after reperfusion, while the rheobase was still significantly higher than control levels (0.50 +/- 0.21 nA, n = 16, P < 0.01). 6. The frequency of repetitive firing evoked by depolarizing current pulses was suppressed within 2 h after reperfusion (n = 6, P < 0.01). The spike frequency increased slightly 2-5 h after reperfusion but was still significantly below the control levels (n = 12, P < 0.01). 7. Spontaneous synaptic activities ceased during ischemia and remained depressed shortly after reperfusion. Spontaneous firing rate was 0.47 +/- 0.81 spikes/s (n = 34) before ischemia. No spontaneous firing was detected within 2 h after reperfusion, and the firing rate gradually returned to preischemic levels 2-5 h after reperfusion (0.28 +/- 0.96 spikes/s, n = 15). Neuronal hyperactivity as indicated by an increased spontaneous firing rate was not observed up to 7 h after reperfusion. 8. Stimulation of the contralateral commissural pathway elicited excitatory postsynaptic potentials (EPSPs) minutes after reperfusion, whereas inhibitory postsynaptic potentials (IPSPs) did not appear until approximately 1 h after reperfusion. Within 2 h after reperfusion, the amplitudes of EPSPs slightly increased compared with those before ischemia, and the duration of EPSPs significantly increased from 18.00 +/- 3.08 ms (n = 5) before ischemia to 26.83 +/- 4.26 ms (n = 6, P < 0.01). The amplitude and duration of EPSPs returned to preischemic levels 4-5 h after reperfusion. 9. Results from the present study indicate that the input resistance and time constant of CA1 pyramidal neurons decrease during cerebral ischemia. After 5 min of forebrain ischemia, the spontaneous neuronal activities, evoked synaptic potentials and excitability of CA1 neurons are transiently suppressed after reperfusion. No hyperactivity was observed up to 7 h after reperfusion.
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PMID:Electrophysiological changes of CA1 pyramidal neurons following transient forebrain ischemia: an in vivo intracellular recording and staining study. 889 Feb 85

The effect of the immunosuppressant FK506 on ischaemic neuronal damage was studied in a rat model of transient cerebral ischemia induced by occlusion of both common carotid arteries in combination with hypotension for 10 min. Neuronal damage was assessed morphologically after 4 days of recovery. Treatment with FK506, given at a dose of 2 mg kg-1 by intraperitoneal injections 30 min prior to ischemia and once daily during recovery, decreased neuronal damage by 52% in the hippocampal CA1 region and by 48% in the temporal cortex. The protection was not due to diminished body temperature or a marked reduction of ischaemia-induced synaptic overflow of glutamate. We propose that FK506 decreases neuronal damage either by inhibiting calcineurin-mediated events or by preserving mitochondrial function.
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PMID:The immunosuppressant FK506 ameliorates ischaemic damage in the rat brain. 889 62

Excitotoxicity involves neuronal depolarization and eventual cell death primarily through excess activation of glutamate receptors. Neuronal cell swelling is considered an early excitotoxic event mediated by ionic influx (mainly Na+ and Cl-) followed by water. Changes in the intrinsic optical signals of nerve tissue correlate with neuronal activity such that light transmittance (LT) increases across the brain slice as cells swell. The present study examined the effects of domoic acid, a potent excitotoxic food contaminant and glutamate analogue, on intrinsic optical signals in the rat hippocampal slice. A brief 1-min exposure to 10 microM domoate at 22 degrees C elevated LT by 58% in the apical dendritic region of CA1 and to a lesser extent in the molecular layer of the upper dentate gyrus. The responses peaked by 5 min and slowly reversed during a 30-min wash. The same responses were evoked by a 1-min application of 10 microM alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) at 22 degrees C. Minor changes were observed in the CA3 region and the lower blade of the dentate gyrus. At 37 degrees C, exposure to 10 microM domoate for 10 min resulted in apparent irreversible neuronal damage in the CA1 and upper dentate regions. The Na+ channel blocker tetrodotoxin (1 microM) eliminated the evoked CA1 population spike but not the LT increase, indicating that the domoate signal is not associated with action potential discharge pre- or post-synaptically. However, the response to domoate at 22 degrees C was reversibly blocked by the nonspecific glutamate receptor antagonist kynurenate and the non-N-methyl-D-aspartate (non-NMDA) receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 6,7-dinitroquinoxaline-2,3-dione (DNQX). The response was not blocked by the NMDA receptor antagonist 2-amino-5-phosphonovaleate (AP-5) nor the kainate receptor blocker gamma-D-glutamylaminomethyl sulfonate (GAMS). Relative tissue resistance (RREL) measured across the CA1 dendritic region increased rapidly in response to domoate and fell slowly over 30 min, which paralleled the LT response described above. The increase in RREL was blocked by kynurenate. We propose that domoate binding to AMPA receptors opens channels mediating ionic influx, presumably Na+ followed passively by Cl-. Water follows, producing prolonged postsynaptic swelling in the CA1 and dentate regions where AMPA receptors are most abundant. At higher temperature this swelling can progress to permanent neuronal injury. Imaging intrinsic optical signals allows a real-time view of early excitotoxic events and may prove useful in assessing potentially therapeutic agents that reduce damage induced by excitotoxic agents or ischemia.
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PMID:Real-time imaging of intrinsic optical signals during early excitotoxicity evoked by domoic acid in the rat hippocampal slice. 890 84

Wistar rats were subjected to transient forebrain ischemia for 30 min. After a survival period of two to three days their brains were fixed and sections were processed for Nauta suppressive method (26) to study postischemic degenerative changes and for glial fibrillary acidic protein (GFAP) to study glial reaction. After two days somatodendritic argyrophilia was evident in the CA1a and CA4 areas. The somata and dendrites of CA1 a pyramidal neurons were intensely argyrophilic, and a clear border zone which separated these neurons from undamaged CA1b neurons was detected. In the CA4 area a few degenerating, probably mossy cells were found. Neuronal degeneration then proceeded rapidly during a 72 h survival period, when the somata and dendrites of complete CA1 and CA2 pyramidal cells became intensively argyrophilic. The area of CA4 was full of degenerated neurons, but the CA3 neurons remained intact. Postischemic glial changes were observed after 48h survival. The rostral part of CA1a area contained a higher concentration of astrocytes in the dendritic layer as well as in the pyramidal layer. These astrocytes revealed features of reactive astrocytes. An intense GFAP immunoreactivity with heavily stained astrocytic figures appeared in the CA2, CA3 dendritic layers, stratum molecular of the DG and hilus. The central region of CA4 area contained various vacuoles with clearly stained astrocytes. By 72 h after ischemia the tissue structure changed in all areas since the pyramidal layer contained shrunken neurons and large vacuoles. The GFAP immunoreactivity in the hippocampus was the same or even higher as observed after two days postischemia, but the astrocytes were seen more closely in the relation with the pyramidal cell layer.
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PMID:Ischemic damage in the hippocampus: a silver impregnation and immunocytochemical study in the rat. 893 16

One major event taking place at the moment of traumatic brain injury in neuronal cells is the occurrence of massive ionic fluxes across the plasma membrane, which can be referred to as traumatic depolarization (TD). Unlike spreading depression, TD can occur over wide brain areas simultaneously. Furthermore, recovery from TD often takes far longer than recovery from ionic perturbation elicited by the passage of a single wave of spreading depression. Neuronal cell damage caused by ischemic brain injury is also initiated by massive ionic fluxes, termed anoxic depolarization. The occurrence of similar ionic events in these two forms of brain injury may account for the genesis of diffuse ischemia-like damage without actual episodes of hypoxia or ischemia in traumatic brain injury. We review the data indicating that excitatory amino acids (EAA) may play a vital role in producing TD, and that such EAA-mediated ionic perturbation is responsible for a number of posttraumatic events including subcellular metabolic dysfunction and cellular responses such as microglial activation and astrocytic transformation. TD may represent one of the most important mechanisms of diffuse neuronal cell dysfunction and damage associated with traumatic brain injury.
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PMID:Role of excitatory amino acid-mediated ionic fluxes in traumatic brain injury. 897 25

In this study the effect of LY 231617, an antioxidant, on spatial learning deficit and on neuronal damage following transient cerebral ischemia was evaluated. Global ischemia was induced by four-vessel-occlusion (4VO) for 20 min in rats. LY 231617 (20 mg/kg i.p.) was administered after onset of reperfusion. One week after surgery spatial learning was tested in the Morris water maze. LY 231617 reduced the increase in escape latency and in swim distance induced by 4VO. Neuronal damage in the CAI sector of the hippocampus produced by 4VO was significantly attenuated by LY 231617. The present data demonstrate that posttreatment with LY 231617 exerts a protective effect on hippocampal neuronal damage and deficits in spatial learning induced by 4VO.
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PMID:The antioxidant LY 231617 ameliorates functional and morphological sequelae induced by global ischemia in rats. 897 59

Glutamate antagonists have been shown to be neuroprotective in animal models of cerebral ischemia. Global cerebral ischemia in rats leads to selective neuronal damage in the hippocampus and striatum. Following ischemia a transient locomotor hyperactivity and a deficit in spatial learning and memory occurs. The aim of the present study was to investigate the potential neuroprotective effect of dextromethorphan, an antagonist at the N-methyl-D-aspartate receptor, with behavioural and histological measures of global ischemia in rats. Global ischemia was induced by four-vessel occlusion (4VO) for 20 min in rats. Dextromethorphan was administered 20 min before induction of ischemia at a dose of 10 or 50 mg/kg. Before and on day 1, 3 and 5 after operation the spontaneous locomotor activity was measured. One week after surgery spatial learning was tested in the Morris water maze. After behavioural testing the animals were sacrificed and the neuronal damage was assessed. Treatment with 50 mg/kg of dextromethorphan reduced the increase in locomotor activity observed on day 1 and 3 after ischemia. In the water maze dextromethorphan reduced the increase in escape latency and in swim distance induced by 4VO. Furthermore, the ischemia-induced reduction in time spent in the quadrant of the former platform position during the probe trial was increased by treatment with dextromethorphan. Neuronal damage in the CA1 sector of the hippocampus and in the dorsolateral striatum produced by 4VO was significantly attenuated by dextromethorphan. The present results demonstrate that protective effects on neuronal damage may be related to an attenuation of deficits in spatial leaning and memory following global ischemia.
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PMID:Dextromethorphan reduces functional deficits and neuronal damage after global ischemia in rats. 900 17

We have studied the beneficial effects of S-adenosyl-L-methionine (SAM) tosylate on blood-brain barrier (BBB) breakdown and neuronal survival after transient cerebral ischemia in gerbils. BBB breakdown experiments were performed in pentobarbital anesthetized gerbils subjected to 10 min of bilateral carotid artery occlusion and 6 h of reperfusion. For BBB breakdown measurements, SAM (120 mg/kg, i.p.) was administered to gerbils just after occlusion and thereafter every hour up to 5 h. Fluorometric measurements quantified the blood-brain permeability tracer, Evans blue (EB). SAM treatment significantly reduced the BBB breakdown as indicated by reduced levels of EB fluorescence. Neuronal count experiments were conducted in gerbils subjected to transient ischemia and 7 days of reperfusion. For neuronal count experiments SAM (15-120 mg/kg) was administered at 6 and 12 h after reperfusion, and twice each day thereafter for 7 days. SAM dose dependently protected the hippocampal CA1 neurons assessed by histopathological methods. SAM has a beneficial effect on the outcome of ischemic injury by reducing the BBB breakdown and neuronal death.
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PMID:Beneficial effects of S-adenosyl-L-methionine on blood-brain barrier breakdown and neuronal survival after transient cerebral ischemia in gerbils. 903 Jul 7


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