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Query: UMLS:C0003129 (Anoxia)
 551 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Interstitial pH (pHo) and field responses (to stratum radiatum stimulation) were recorded simultaneously with double-barrelled microelectrodes in the CA1 region of hippocampal slices from Sprague-Dawley rats. 2. Both the relative acidity and amplitude of field responses increased with depth, reaching a maximum near the centre of the slice. When the temperature was raised from 22 to 37 degrees C, this pHo gradient was greater than 2 times steeper, but the field responses were much diminished. 3. Standard anoxic tests (substituting 95% N2 + 5% CO2 for 95% O2 + 5% CO2, for 2 min) tended to reduce pHo and population spikes, but these effects were highly temperature sensitive: at approximately 22 degrees C the blocking rate was only 12.3 +/- 4.6% and delta pHo -0.018 +/- 0.0157 units, both per minute; corresponding changes at 34-35 degrees C were 67.6 +/- 11.9% and -0.065 +/- 0.0046 units per minute. Highly significant linear correlations between rates of block and delta pHo gave a mean slope of 90.4 +/- 17.6% per 0.1 unit of acid change. 4. Anoxia caused similar temperature-dependent increases in acidity in stratum pyramidale and radiatum, but in the latter field responses (EPSPs) were much less depressed after 2 min of anoxia. 5. When slices were superfused with acid medium (low [HCO3-]), much greater reductions in pHo were needed to depress responses, giving a mean slope of 17.7% per 0.1 pH unit. 6. In glucose-free medium, there was a slow alkaline shift in pHo (0.13 +/- 0.036 units); population spikes and the acid transients evoked by anoxia disappeared. 7. It was concluded that acidosis cannot be the immediate cause of the similar depressions of postsynaptic excitability seen during anoxia and hypoglycaemia. 8. In further tests, DL-p-hydroxyphenyl-lactic acid, a blocker of lactate transport, failed to diminish acid transients evoked by anoxia, indicating that these are not mediated principally by lactate transport.
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PMID:Acidosis and blockade of orthodromic responses caused by anoxia in rat hippocampal slices at different temperatures. 235 75

1. The effects of brief anoxia (2-4 min) on membrane currents--especially the tetrodotoxin (TTX)-insensitive, Cd2+-sensitive slow inward currents, presumed to be Ca2+ currents--were studied by single-electrode voltage clamp in CA1 and CA3 neurons in submerged hippocampal slices from adult and newborn Wistar rats (PN1-13). 2. In mature neurons, anoxia had no effect on Q-type inward relaxations, but slowly activating C-type outward currents were depressed. The most striking change was the suppression of Ca inward currents (especially the slowly inactivating L-type, by greater than 95%). This effect of anoxia was not sensitive to the N-methyl-D-aspartate (NMDA) receptor blocker, D-aminophosphonovalerate. Anoxia also reversibly abolished the NMDA-evoked inward current. 3. In neurons from newborn animals (PN1-6), Q-type inward relaxations and postanoxic outward currents were very small or undetectable. The slow inward (Ca) currents were smaller than in mature cells, but they showed a clearer separation between low-threshold, fast-inactivating and high-threshold, slowly inactivating currents. Both types of current were more resistant to anoxia (mean depression of L-type was by only 53.3 +/- 5.6%, mean +/- SE). 4. In such immature neurons, the NMDA-evoked inward currents were also more resistant to anoxia. 5. By PN7-13, increasing maturation was reflected in 1) larger voltage-dependent inward currents, 2) increasingly evident Q-type relaxations and postanoxic outward currents, and 3) near-complete blockade of inward currents by anoxia (at PN11-13, mean depression of L-type currents was by 98.5 +/- 1.5%).
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PMID:Anoxia on slow inward currents of immature hippocampal neurons. 255 81

1. The reversible blocking effect of brief anoxia (2-4 min) on synaptic transmission was studied in submerged hippocampal slices (kept mostly at 34 degrees), obtained from adult (greater than 120 g) and very young (6-50 g) Wistar rats. Excitatory postsynaptic potentials (EPSPs) were recorded with extra- and intracellular electrodes, sometimes simultaneously: in CA1, they were evoked by stratum radiation stimulation, in CA3 by hilar stimulation. 2. In slices from adults, EPSPs in CA1 were depressed by 90% after 2 min of anoxia, and postanoxic recovery was relatively slow (one-half recovery times 4.0 +/- 0.23 min, mean +/- SE). EPSPs in CA3 were consistently more resistant, especially those generated by mossy fibers; after 2 min of anoxia, these were reduced by only 14.7 +/- 5.4%. 3. In newborn animals (PN1-4), both intra- and extracellular EPSPs (but no population spikes) could be recorded in CA1. Although smaller and more fatigable than in the adult, they were much more resistant to anoxia, after 2 min being reduced by only 44.1 +/- 8.8%; and they were not abolished even after 6-7 min. On the other hand, postanoxic recovery was very rapid, being one-half complete in 2.4 +/- 0.48 min. Only large and very prolonged (giant) depolarizing PSPs [probably inhibitory postsynaptic potentials (IPSPs)] could be recorded in CA3 neurons; they were rapidly blocked by anoxia. 4. In older pups (PN6-21), the CA1 EPSPs became progressively more sensitive to anoxia. At the end of the second week, they were as rapidly blocked as in slices from adults; but postanoxic recovery remained quicker throughout this period. In CA3, EPSPs could now be evoked that were as resistant to anoxia as in adult slices. 5. In both CA1 and CA3 neurons from adult rats, anoxia (for 2-3 min) reduced the input resistance (RN) by 45.7 +/- 6.25%. In CA1 neurons, there was most often some hyperpolarization (-7.2 +/- 1.8 mV), which was less consistent in CA3 cells. The return of O2 typically led to a second (postanoxic) phase of hyperpolarization (-7.9 +/- 1.93 mV). 6. At PN1-4, the resting potential (Vm) of most cells had to be maintained by current injection; the input resistance (RN) of CA1 neurons was 70% higher than in mature cells, and there was little time-dependent inward rectification. Anoxia produced no regular changes in Vm, and reductions in RN were very small (by only 9.6 +/- 5.0%). A postanoxic hyperpolarization was seen in only 2 neurons out of 11.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Anoxia produces smaller changes in synaptic transmission, membrane potential, and input resistance in immature rat hippocampus. 280 8

Immunohistochemical staining for the calcium-binding protein calbindin-D28k (CaBP) was combined with Lucifer Yellow (LY) identification and intracellular recording of changes in membrane parameters of pyramidal neurons in CA2, CA1, and the subiculum of rat hippocampal slices during brief exposure (4.0 +/- 0.19 min) to N2. Anoxia evoked either a depolarization or hyperpolarization of membrane potential (VM) (+21.5 +/- 2.79 mV above VM = -70.5 +/- 1.50 mV, n = 30 and -7.2 +/- 0.72 mV below VM = -68.2 +/- 1.34 mV, n = 24, respectively) and a fall in membrane resistance of approximately 20%. Differences in the response could be correlated with the presence or absence of CaBP and the localization of neurons in different layers of stratum pyramidale and sectors of the hippocampus. For neurons immunopositive for calbindin (CaBP(+)), depolarization was observed more frequently (83%) than hyperpolarization (17%); in contrast, 44% of responses of calbindin-negative (CaBP(-)) neurons were depolarizing and 56% were hyperpolarizing. Depolarizations of CaBP(+) neurons were more gradual in slope, and more rapidly reached a plateau in comparison with those recorded in CaBP(-) neurons. Responses of neurons in the superficial layer of stratum pyramidale (in which 79% of CaBP(+) pyramidal neurons were situated) were mainly depolarizing (91%), while for those in the deep layer (which contained 89% of the CaBP(-) cells) such responses were observed less often (45%). Depolarization was also more common than hyperpolarization for cells located in CA2/CA1c/CA1b (63%) than in the CA1a/subicular region (37%). The depolarizing response of the majority of pyramidal neurons which are CaBP(+), superficial, and closer to CA3 may reflect an efficient buffering of intracellular Ca2+, which maintains a low [Ca2+]i, steep gradient for Ca2+ influx and may facilitate the movement of Ca2+ away from points of entry. The neurons which are CaBP(-), deep, and closer to subiculum and in which N2 evokes hyperpolarization, on the other hand, may have a sustained elevation/accumulation of cytosolic Ca2+ which could activate K+ conductance, inhibit Ca2+ influx, and stabilize the membrane potential. These experiments provide a functional correlate for CaBP and suggest that it may have a significant role in Ca2+ homeostasis and the determination of selective neuronal vulnerability.
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PMID:Correlation of anoxic neuronal responses and calbindin-D28k localization in stratum pyramidale of rat hippocampus. 778 44

Anoxia produces deleterious effects on synaptic transmission in the hippocampal slice preparation. A proposed source of damage is the superoxide radical (.O2-) produced during the earlier period of reoxygenation. The present study tested the effects of a synthetic, catalytic superoxide radical scavenger (EUK-8) on CA1 pyramidal cell responses elicited by electrical stimulation of the Schaffer-commissural pathway after severe anoxic episodes. Following reoxygenation, slices incubated with EUK-8 (50 microM) exhibited significantly better recovery of excitatory postsynaptic potentials (EPSPs) than control slices. In addition, repeated episodes of anoxia produced irreversible loss of synaptic transmission in the majority of control slices (93 +/- 7%, n = 15), compared to a small fraction in EUK-8-incubated slices (27 +/- 12%, n = 15). A thiobarbituric acid (TBA) test was used to assess the effect of EUK-8 on lipid peroxidation elicited in hippocampal slices by acidosis and lactic acid (pH 5.0 and 30 mM lactic acid). Incubation in the presence of EUK-8 totally prevented the increase in lipid peroxidation produced by acidosis and lactic acid in both the incubation medium and the slice homogenates. These results indicate that a superoxide scavenger like EUK-8 prevents damage produced by acidosis and anoxia in hippocampal slices and suggest the possibility of using this type of molecule under various pathological conditions.
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PMID:Effects of EUK-8, a synthetic catalytic superoxide scavenger, on hypoxia- and acidosis-induced damage in hippocampal slices. 796 13

Anoxia is believed to cause nerve injury and death in part, by inducing sustained, elevated levels of intracellular Ca2+. The increased concentration of intracellular Ca2+ is capable, by itself, of inducing nerve injury and death, even without the added stress of anoxia. However, we have recently shown that an increased level of intracellular Ca2+ is not necessary for anoxia-induced CA1 nerve injury. Since we have observed that extracellular Na+ decreases during anoxia, we studied the role of extracellular Na+ in anoxia-induced nerve injury. Removal of extracellular Na+ and its replacement with the impermeant cation N-methyl-D-glucamine (NMDG+) completely protected freshly dissociated CA1 neurons during and after severe anoxia, for up to 90 min. Intracellular Ca2+ decreased during anoxia, recovering during reoxygenation. Propidium iodide was excluded from the neurons for as long as Na+ was absent. Addition of Na+ (by replacing NMDG+) following anoxia resulted in rapid bleb formation, swelling and intracellular Ca2+ rise. Removal of Na+ before the rupture of blebs caused either shrinkage or pinching off of blebs so that the neuron apparently returned to its previous undisturbed state.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Removal of extracellular sodium prevents anoxia-induced injury in freshly dissociated rat CA1 hippocampal neurons. 801 52

Cerebral ischemia induces major neuronal morphological alterations. It is not clear, however, whether this is directly caused by O2 deprivation. To determine the effect of hypoxia on cytoskeletal structures and neuronal morphology, we performed experiments and examined anoxia-induced changes in microtubule-associated protein 2 (MAP2) and cell morphology in hippocampal slices in vitro. Anoxia (measured PO2 = 0 Torr) induced a marked loss in dendritic MAP2 immunoreactivity and cell swelling of hippocampal neurons by 2 h after O2 reinstitution. These changes were severe in CA1 and CA3 neurons and comparatively mild in dentate gyrus neurons. Quantitative analysis showed that 10 min of anoxia induced a 30% loss of MAP2-positive dendrites but this increased to 70% after 30 min of anoxia. A concurrent major increase in somata area of about 100% and 200% was observed in CA1 and CA3 neurons respectively. Somata area in the lower dentate gyrus, however, increased either insignificantly or by only 30% for the respective periods of anoxia. These results suggest that deprivation of O2 can by itself induce a major loss in dendritic MAP2 immunoreactivity and changes in cell morphology in hippocampal neurons. These alterations occur rapidly after hypoxia, and the severity of these changes is directly related to the duration of anoxia and brain region in the hippocampus.
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PMID:Acute anoxia-induced alterations in MAP2 immunoreactivity and neuronal morphology in rat hippocampus. 836 56

1. The effects of anoxia on excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs, respectively) evoked by electrical stimulation in the stratum radiatum were studied in morphologically and electrophysiologicaly identified lacunosum-moleculare (LM) interneurons of the CA1 region of rat hippocampal slices. The blind whole cell patch-clamp technique was used, and anoxia was induced by superfusion of the slice with an anoxic artificial cerebral spinal fluid saturated with 95% N2-5% CO2 for 4-6 min. 2. In LM interneurons, anoxia generated currents similar to those in pyramidal cells, the most prominent being anoxic and postanoxic outward currents. The adenosine A1 type receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 200 nM) did not significantly affect anoxia-generated currents. 3. EPSCs and polysynaptic IPSCs (pIPSCs) evoked in LM interneurons by "distant" stimulation (> 1 mm) in the stratum radiatum were strongly depressed by anoxia and recovered upon reoxygenation. 4. Responses to pressure application of glutamate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and N-methyl-D-aspartate (NMDA) were not significantly affected by anoxia, suggesting that the suppression of EPSCs is due to presynaptic mechanisms. 5. DPCPX (200 nM) prevented anoxia-induced suppression of EPSCs, suggesting that this suppression was mediated by presynaptic A1 adenosine receptors. 6. Monosynaptic IPSCs evoked by "close" stimulation (< 0.5 mm) in the stratum radiatum, in the presence of glutamate-receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20 microM) and D-2-amino-5-phosphopentanoate (APV; 50 microM), were reversibly depressed but not blocked by anoxia. 7. Anoxia depressed monosynaptic GABAA receptor-mediated IPSCs (monosynaptic IPSCAs) by inducing a positive shift in the reversal potential and a decrease in slope conductance. Responses to pressure-applied isoguvacine, a GABAA receptor agonist, were reversibly depressed by anoxia, again because of a positive shift in reversal potential and decrease in conductance. Anoxic effects on slope conductances and reversal potential of isoguvacine responses and monosynaptic IPSCA coincided, suggesting that evoked transmitter release from GABAergic terminals was not affected by anoxia. 8. Anoxic depression of monosynaptic GABAB receptor-mediated IPSCs (monosynaptic IPSCBs) was due to a decrease in the slope conductance of monosynaptic IPSCB. In contrast to EPSCs, DPCPX (200 nM) failed to prevent anoxia-induced depression of mIPSCA and mIPSCB. 9. Paired-pulse depression of monosynaptic IPSCs, partially mediated by presynaptic GABAB receptors, was not affected by anoxia. 10. These data provide direct evidence for the hypothesis that inhibitory interneurons of CA1 stratum LM are functionally disconnected from excitatory inputs by anoxia. This disconnection underlies the preferential block by anoxia of IPSCs recorded in pyramidal cells, and it may occult the postsynaptic modifications in GABAA and GABAB responses. This disconnection involves adenosine-dependent inhibition of glutamate release from excitatory terminals. GABA release and its modulation by presynaptic GABAB receptors, both known to be insensitive to adenosine, seems to be resistant to anoxia.
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PMID:Hippocampal CA1 lacunosum-moleculare interneurons: comparison of effects of anoxia on excitatory and inhibitory postsynaptic currents. 859 2

The role of the adenosine A1 receptor in the modulation of anoxia-induced synaptic glutamate release was examined in CA1 pyramidal neurons by whole-cell voltage-clamp recording in the rat hippocampal slice preparation. Anoxia leads to an increased action potential-independent synaptic glutamate release in the form of a higher frequency of miniature excitatory postsynaptic currents (mEPSCs). This increase is not significantly affected when slices are preincubated in the adenosine A1 receptor antagonist, 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX). A second population of spontaneous inward currents, however, occurs in DPCPX-treated slices during a well-defined period following the onset of anoxia. Their suppression by glutamate antagonists, tetrodotoxin, or by the cutting of the Schaffer collateral pathway indicates that they represent action potential-dependent, glutamatergic excitatory postsynaptic currents (ap-EPSCs) originating from CA3 pyramidal neurons. CA3 neurons were examined in current-clamp whole-cell patch mode to determine the origin of this increased orthodromic excitation. After the onset of anoxia, CA3 cells initially exhibit a small depolarization or hyperpolarization associated with a decrease in input resistance. This is followed by transient depolarization (the depolarizing "nub"), which is associated with an increase in input resistance. The nub evoked single as well as bursts of action potentials in CA3 neurons. The occurrence of these CA3 nub-elicited action potentials coincides with that of ap-EPSCs recorded in the CA1 cells. Recording with cesium- rather than standard potassium-containing electrodes results in the suppression of the nub and its associated increase in input resistance. In conclusion we have shown that adenosine tone plays an important role in suppressing anoxia-induced spontaneous ap-EPSCs but not action potential-independent mEPSCs in CA1 neurons. These EPSCs originate from a depolarization in CA3 pyramidal neurons, which is associated with an increase in resistance. This previously undescribed phenomenon likely results from a decrease in the conductance of an unidentified potassium channel.
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PMID:Adenosine A1 antagonism increases specific synaptic forms of glutamate release during anoxia, revealing a unique source of excitation. 884 22

In in vitro rat hippocampal slices, a short period of transient anoxia caused a lasting increase in the amplitude of the compound action potential (population spike, PS) that was evoked in CA1 by stimulation of the Schaffer collaterals. No such increase was seen over a comparable period of time in slices that were not subjected to anoxia. The appearance of such an increase was dependent on the duration of anoxia. Anoxia of 1 min duration did not cause any increase, anoxia lasting 2 min caused a nonsignificant increase, while 3 min of anoxia caused a lasting and statistically significant increase in PS amplitude. Addition of creatine, a compound that is known to afford protection against severe neuronal damage from longer periods of anoxia, prevented PS potentiation at a concentration of 10 mM, but not at a concentration of 1 mM. In addition, while 1 mM creatine by itself did not show any effect on PS amplitude of control slices, 10 mM creatine decreased PS amplitude also in such control slices, that had not been exposed to anoxia. These data demonstrate that this postanoxic hyperexcitability is caused by mechanisms that are little sensitive to the protection that in other contexts is provided by creatine. We suggest that understanding the mechanisms of postanoxic hyperexcitability may help understand the pathophysiology of the epileptic seizures that sometimes occur at the time of an ischemic stroke.
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PMID:Effects of exogenous creatine on population spike amplitude and on postanoxic hyperexcitability in brain slices. 1256 Jan 25


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