Direct Current Potential Research Articles

Scalp recorded direct current (DC) potential shifts associated with food intake in hungry humans

In humans, eating is assumed to be regulated within a neuronal circuitry integrating hypothalamic ‘feeding centers’ with neocortical regions. Here, DC potentials were recorded in food deprived men to demonstrate a graded tuning of neocortical excitability in conjunction with meal ingestion. In the beginning of food ingestion a pronounced negative DC potential shift developed ( P<0.01) which was replaced by a gradual positive potential shift reaching a maximum within 5 min after cessation of food intake ( P<0.05). Both negative and positive shifts showed a widespread cortical distribution. The initial negative DC potential presumably reflecting increased depolarisation of apical cortical dendrites, may serve to facilitate eating behavior. The succeeding positivity points to a growing inhibitory influence on cortical processing with increasing satiety that may support termination of meal intake.

In Vivo Microvascular Analysis of Albumin Therapy in Focal Cerebral Ischemia: Dynamic Laser Confocal Microscopy.

P65 To study whether hemodynamic alterations are responsible for the marked neuroprotective effect of albumin in focal ischemia, we used a newly developed method for studying brain microcirculation, combining in vivo fluorescence microscopy of labeled erythrocytes and plasma with confocal microscopy. Sprague-Dawley (SD) rats were anesthetized with halothane/nitrous oxide, and a cranial window was placed in the dorsolateral frontoparietal cortex. Cortical direct current (DC) potential was also recorded. Rats received 2h middle cerebral artery occlusion (MCAo) by intraluminal suture coated with poly-L-Lysine and were treated with human albumin (Alb, n=4, 1.25g/kg) or saline (Sal, n=3) following 30 min of recirculation. Video images of cortical vessels were continually acquired and were digitized off-line to measure diameters and flow velocities. In separate experiments, anesthetized SD rats received 2h MCAo and were treated with Alb (2.5g/kg; n=6),) or Sal (n=5) 15 min after recirculation. Laser Doppler Perfusion Imaging (LDPI) was measured. MCAo was associated with arteriolar dilatation and slowing of capillary and venular perfusion together with recurrent DC depolarizations. During the first 15–30 min of postischemic recirculation, prominent foci of vascular stasis developed within cortical venules, associated with thrombus-like stagnant foci and adherent intra-venular corpuscular structures. Sal administration failed to affect these phenomena, while Alb therapy was followed in many cases by improvement of venular flow and disappearance of adherent corpuscules and thrombotic material. In the LDPI study, CBF declined during MCAo and rose initially with recirculation (to 130%) identically in Alb and Sal rats. Alb led to an additional sustained CBF increase of 17% (p&lt;.0001), but Sal caused no further change. These results support the strong beneficial effect of Alb therapy in focal ischemia and suggest its possible utility in treating patients with acute ischemic stroke. Supported by AHA Init. Invest. Award, NIH Grant NS05820 and an equipment loan from Moor Instruments, Ltd.

The effects of anesthetics on cortical spreading depression elicitation and c-fos expression in rats.

The effects of anesthetics on the generation of cortical spreading depression (CSD) were investigated. Volatile anesthetics halothane, isoflurane, sevoflurane (0.5, 1.0, and 2.0 MAC), and the intravenous anesthetic pentobarbital were studied. Cortical spreading depression was induced by 3M-KCl applied to a surface of brain cortex for 30 minutes. Direct current (DC) potential was recorded, and the number, amplitude, and duration of CSDs were observed. With increasing concentrations of each volatile anesthetic, there was a dose-related reduction in CSD frequency but not in CSD amplitude. At 2.0 MAC of sevoflurane the suppression of CSD was less than with the other volatile anesthetics. In addition, the influence of anesthetics on expression of c-fos mRNA was investigated. Additional animals anesthetized by isoflurane or sevoflurane were studied. Five CSDs were elicited by electric stimulation (0.5 mV, 1 second) in each animal. In situ hybridization with 35S-labeled oligonucleotides was used to evaluate the level of c-fos mRNA. The expression of c-fos was observed in the hemisphere in which CSD was elicited, but there was no difference in expression of c-fos among the groups. We conclude that volatile anesthetics can induce suppression of CSD elicitation in a dose dependent manner, but that at high concentrations sevoflurane is significantly less effective than other volatile agents. Pentobarbital has the least effect on KCl-induced CSD. These data suggest that the choice of anesthetics can impact the results of studies examining membrane depolarization and the ionic changes initiated by CSD.

Acute protective effect of nimodipine and dimethyl sulfoxide against hypoxic and ischemic damage in brain slices

Nimodipine and dimethyl sulfoxide (DMSO) were tested (alone and in combination) regarding their ability to increase hypoxic tolerance of brain slices under ‘hypoxic’ (deprivation of oxygen) or ‘ischemic’ (hypoxia+withdrawal of glucose) conditions. Direct current (DC) and evoked potentials were recorded in the CA1 region of hippocampal slices of adult guinea pigs. After induction of hypoxia or ischemia, the latency of anoxic terminal negativity (ATN) of the DC potential was determined during superfusion with artificial cerebrospinal fluid alone (aCSF), and during superfusion with aCSF containing DMSO [0.1% (14.1 mmol/l) and 0.4% (56.3 mmol/l)] with the addition of nimodipine (40 μmol/l). Latencies of ATN with first hypoxia were 6.7±3.7 min in the control group, 9.3±4.2 min in the 0.4% DMSO group and 12.3±5.5 min ( P=0.007) in the nimodipine/0.4% DMSO group. Latencies of ATN with first ischemia were 2.9±2 min in the control group, 4.1±1.6 min in the 0.1% DMSO group, 7.1±3.9 min in the 0.4% DMSO group ( P=0.006), 5.3±1.5 min in the nimodipine/0.1% DMSO group and 7.6±3 min ( P<0.001) in the nimodipine/0.4% DMSO group. DMSO (0.4%), either alone or in combination with nimodipine, increase the latency of the ATN after acute onset of hypoxia and ischemia.

Scalp recorded direct current potential shifts associated with quenching thirst in humans

As an indicator of cortical excitability, direct current (DC) potentials were recorded from thirsted subjects before, during and after drinking 400 ml of water. Self-rated thirst was distinctly reduced after drinking. Compared with control conditions in which the subjects remained thirsty, during drinking a widespread negative potential shift occurred averaging over -70 microV at Cz. At the transition from the consumatory phase to the postconsumption phase, a slow positive potential shift commenced that was most pronounced over the anterior cortex (averaging over +40 microV at Fz) and persisted for more than 3 min after drinking. Control conditions excluded muscle activity, ocular movements, and changes in body fluid and serum osmolality as possible non-neuronal sources of the DC-potential changes. The sequence of negative and positive potential shifts associated with drinking indicates a coordinate regulation of cortical excitability that may facilitate consumatory behavior and its context-dependent encoding into memory.

Scalp recorded direct current potential shifts associated with quenching thirst in humans

As an indicator of cortical excitability, direct current (DC) potentials were recorded from thirsted subjects before, during and after drinking 400 ml of water. Self-rated thirst was distinctly reduced after drinking. Compared with control conditions in which the subjects remained thirsty, during drinking a widespread negative potential shift occurred averaging over −70 μV at Cz. At the transition from the consumatory phase to the postconsumption phase, a slow positive potential shift commenced that was most pronounced over the anterior cortex (averaging over +40 μV at Fz) and persisted for more than 3 min after drinking. Control conditions excluded muscle activity, ocular movements, and changes in body fluid and serum osmolality as possible non-neuronal sources of the DC-potential changes. The sequence of negative and positive potential shifts associated with drinking indicates a coordinate regulation of cortical excitability that may facilitate consumatory behavior and its context-dependent encoding into memory.

Changes in direct current (DC) potentials and infra-slow EEG oscillations at the onset of the luteinizing hormone (LH) pulse.

An essential function of the neuroendocrine system lies in the coordination of hypothalamo-pituitary secretory activity with neocortical neuronal activity. Cortical direct current (DC) potential shifts and EEG were monitored in conjunction with the circulating concentration of luteinizing hormone (LH) in humans while asleep to assess a hypothalamic-neocortical interaction. The onset of an LH pulse was accompanied (i) at frontocortical locations by a transient positive DC potential shift of approximately 3 min duration and peak amplitude 50 microV; (ii) at frontal and central locations by an increase in power of infra-slow EEG oscillations for periodicities between 64 and 320 s. Results uniquely demonstrate a coupling of hypothalamo-pituitary activity with regulation of neocortical excitability.

Products of hemolysis in the subarachnoid space inducing spreading ischemia in the cortex and focal necrosis in rats: a model for delayed ischemic neurological deficits after subarachnoid hemorrhage?

The pathogenesis of delayed ischemic neurological deficits after subarachnoid hemorrhage has been related to products of hemolysis. Topical brain superfusion of artificial cerebrospinal fluid (ACSF) containing the hemolysis products K+ and hemoglobin (Hb) was previously shown to induce ischemia in rats. Superimposed on a slow vasospastic reaction, the ischemic events represent spreading depolarizations of the neuronal-glial network that trigger acute vasoconstriction. The purpose of the present study was to investigate whether such spreading ischemias in the cortex lead to brain damage. A cranial window was implanted in 31 rats. Cerebral blood flow (CBF) was measured using laser Doppler flowmetry, and direct current (DC) potentials were recorded. The ACSF was superfused topically over the brain. Rats were assigned to five groups representing different ACSF compositions. Analyses included classic histochemical and immunohistochemical studies (glial fibrillary acidic protein and ionized calcium binding adaptor molecule) as well as a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay. Superfusion of ACSF containing Hb combined with either a high concentration of K+ (35 mmol/L, 16 animals) or a low concentration of glucose (0.8 mmol/L, four animals) reduced CBF gradually. Spreading ischemia in the cortex appeared when CBF reached 40 to 70% compared with baseline (which was deemed 100%). This spreading ischemia was characterized by a sharp negative shift in DC, which preceded a steep CBF decrease that was followed by a slow recovery (average duration 60 minutes). In 12 of the surviving 14 animals widespread cortical infarction was observed at the site of the cranial window and neighboring areas in contrast to findings in the three control groups (11 animals). The authors conclude that subarachnoid Hb combined with either a high K+ or a low glucose concentration leads to widespread necrosis of the cortex.

Solid-state amperometric sensor for the In-situ monitoring of slag composition and transport properties

Open-circuit potential (OCP) measurements with zirconia-based sensors have been used for several decades in the metals industries to determine the oxidation state of high-temperature melts. Although amperometric techniques are known to provide additional kinetic and compositional analysis of the system, they have not been utilized by the metals industries to the same extent. In this work, three different amperometric techniques were examined to monitor high-temperature slags by utilizing zirconia-based sensors. Applied direct current (DC) potential steps and impedance frequency sweeps at fixed applied DC potentials were shown to clearly distinguish between slags having the same oxidation state but different quantities of FeOx in low concentrations. The techniques were also shown to reveal information on the transport properties, slag structures, dissociable oxide type, and buffering capacity of the slag to a given oxidation state. The third technique, coulometric titration, was shown to easily differentiate between slags containing different quantities of FeOx in larger concentrations. The ion-selective membrane properties of the zirconia allowed the coulometric titration to proceed at current efficiencies near 100 pct. This may be useful in developing technology for the recovery of metals from oxide waste streams.

Pharmacological investigation into the involvement of nitric oxide in K+-induced cortical spreading depression.

Cortical spreading depression (CSD) is a transient, local disruption of cellular ionic homeostasis that propagates slowly across the cerebral cortex. As previous data have suggested a possible link between nitric oxide (NO) formation and CSD, we have examined whether CSD is suppressed by local inhibition of NO synthesis with 7-nitroindazole (7-NINA), a compound which may have a greater selectivity for the neuronal NO synthase isoform. Multifunctional microdialysis probes were implanted in the cortex of halothane-anaesthetised rats, and used for (1) elicitation of repetitive CSD by perfusion of 160 mM K+ through the probe, (2) recording of CSD as a negative shift of the extracellular direct current (DC) potential, and (3) perfusion of 7-NINA before and during CSD elicitation. Elicitation of CSD was moderately inhibited by 1 mM 7-NINA in the perfusion medium, as shown in one treated group (n=8) by a significant reduction of both number (from 5.1+/-0.4 to 3.6+/-0.4; P<0.05) and cumulative DC negativity (from 16.4+/-0.7 mV x min to 13.3+/-0.9 mV x min; P<0.01). However, effective concentrations of 7-NINA were at least 100-fold higher than its Ki for the target enzyme in vitro, the moderate inhibition of CSD by 7-NINA was not reversed by the NO precursor, L-arginine, and the amplitude of the K+-induced sustained DC potential negative shift was also reduced significantly by 7-NINA (from 27.9+/-0.9 mV to 23.9+/-1.2 mV; P<0.05). These data do not support the hypothesis that NO formation contributes to the elicitation of CSD by high extracellular K+. The finding that 7-NINA reduced the intensity of K+-induced depolarisation may be relevant to previous investigations that used this drug to examine the role of NO in the modulation of K+-induced neurotransmitter release.

Effects of clomethiazole on spreading depression in the rat hippocampal slice

Clomethiazole is neuroprotective in a variety of animal models of ischaemic stroke, but the mechanism is unclear. This study examined whether clomethiazole is able to modify spreading depression elicited in rat hippocampal slices. When spreading depression was induced by superfusion with high K + medium (50 mM), clomethiazole at 100 μM reduced its duration. Both the amplitude and duration of spreading depression were reduced at 200 μM. Clomethiazole at 200 μM tended to reduce the amplitude of the K +-induced shift in direct current (DC) potential but this was not statistically significant. When a pair of K + pulses were presented, 30 min apart, the second produced a smaller DC potential than the first. Clomethiazole at 200 μM increased the size of the ratio of these responses. Superfusion with a hypoxic solution induced spreading depression observed as a shift in the DC field potential. The amplitude of this was decreased significantly by clomethiazole at 200 μM. With intracellular recordings, the effects of clomethiazole were quantified by measuring the time from the peak K +-induced depolarisation to the recovery of membrane potential following the period of hyperpolarisation. Clomethiazole did not reduce this period significantly. It is concluded that clomethiazole can reduce some forms of spreading depression, but only at the higher concentrations tested. It is unlikely that this effect contributes to its neuroprotective properties.

Abstracts of literature

Abstracts of literature

SB-220453, a potential novel antimigraine agent, inhibits nitric oxide release following induction of cortical spreading depression in the anaesthetized cat.

Profound nitric oxide release associated with cortical spreading depression (SD), has been implicated in stroke, traumatic brain injury and migraine pathophysiology. SB-220453 represents a mechanistically novel, well-tolerated class of compounds which may have therapeutic potential in the treatment of conditions associated with neuronal hyperexcitability and inflammation. The aim of the present study was to investigate the effects of SB-220453 on the nitric oxide (NO) release associated with SD in the anaesthetized cat. In vehicle treated animals, KCl application for 6 min to the cortical suface produced repeated changes in extracellular direct current field potential with associated NO release. This activity was sustained for a median duration of 55 min (25-75% range, 32-59 min) and 59 min (25-75% range, 34-59 min), respectively. SB-220453 (1, 3 and 10 mg/kg i.p.) produced a dose-related inhibition of this activity and at the highest dose tested, the median duration of changes in extracellular field potential and NO release were reduced to 4 min (25-75% range, 4-5 min) and 5 min (25-75% range, 5-5 min), respectively. No effect was observed on basal systemic haemodynamic parameters or resting cerebral laser Doppler blood flux at any of the doses of SB-220453 tested. SB-220453 therefore represents a novel compound to assess the potential benefit of inhibiting SD associated nitric oxide release in neurological disease.

The relationship between the apparent diffusion coefficient measured by magnetic resonance imaging, anoxic depolarization, and glutamate efflux during experimental cerebral ischemia.

A reduction in the apparent diffusion coefficient (ADC) of water measured by magnetic resonance imaging (MRI) has been shown to occur early after cerebrovascular occlusion. This change may be a useful indicator of brain tissue adversely affected by inadequate blood supply. The objective of this study was to test the hypothesis that loss of membrane ion homeostasis and depolarization can occur simultaneously with the drop in ADC. Also investigated was whether elevation of extracellular glutamate ([GLU]e) would occur before ADC changes. High-speed MRI of the trace of the diffusion tensor (15-second time resolution) was combined with simultaneous recording of the extracellular direct current (DC) potential and on-line [GLU]e from the striatum of the anesthetized rat. After a control period, data were acquired during remote middle cerebral artery occlusion for 60 minutes, followed by 30 minutes of reperfusion, and cardiac arrest-induced global ischemia. After either focal or global ischemia, the ADC was reduced by 10 to 25% before anoxic depolarization occurred. After either insult, the time for half the maximum change in ADC was significantly shorter than the corresponding DC potential parameter (P < 0.05). The [GLU]e remained at low levels during the entire period of varying ADC and DC potential and did not peak until much later after either ischemic insult. This study demonstrates that ADC changes can occur before membrane depolarization and that high [GLU]e has no involvement in the early rapid ADC decrease.

In Vivo Microvascular Analysis of Albumin Therapy in Focal Cerebral Ischemia: Dynamic Laser Confocal Microscopy.

P65 To study whether hemodynamic alterations are responsible for the marked neuroprotective effect of albumin in focal ischemia, we used a newly developed method for studying brain microcirculation, combining in vivo fluorescence microscopy of labeled erythrocytes and plasma with confocal microscopy. Sprague-Dawley (SD) rats were anesthetized with halothane/nitrous oxide, and a cranial window was placed in the dorsolateral frontoparietal cortex. Cortical direct current (DC) potential was also recorded. Rats received 2h middle cerebral artery occlusion (MCAo) by intraluminal suture coated with poly-L-Lysine and were treated with human albumin (Alb, n=4, 1.25g/kg) or saline (Sal, n=3) following 30 min of recirculation. Video images of cortical vessels were continually acquired and were digitized off-line to measure diameters and flow velocities. In separate experiments, anesthetized SD rats received 2h MCAo and were treated with Alb (2.5g/kg; n=6),) or Sal (n=5) 15 min after recirculation. Laser Doppler Perfusion Imaging (LDPI) was measured. MCAo was associated with arteriolar dilatation and slowing of capillary and venular perfusion together with recurrent DC depolarizations. During the first 15–30 min of postischemic recirculation, prominent foci of vascular stasis developed within cortical venules, associated with thrombus-like stagnant foci and adherent intra-venular corpuscular structures. Sal administration failed to affect these phenomena, while Alb therapy was followed in many cases by improvement of venular flow and disappearance of adherent corpuscules and thrombotic material. In the LDPI study, CBF declined during MCAo and rose initially with recirculation (to 130%) identically in Alb and Sal rats. Alb led to an additional sustained CBF increase of 17% (p

A glycine site antagonist ZD9379 reduces number of spreading depressions and infarct size in rats with permanent middle cerebral artery occlusion.

Spreading depressions (SDs) occur in experimental focal ischemia and contribute to lesion evolution. N-methyl-D-aspartate (NMDA) antagonists inhibit SDs and reduce infarct size. The glycine site on the NMDA receptor complex offers a therapeutic target for acute focal ischemia, potentially devoid of many side effects associated with competitive and non-competitive NMDA antagonists. We evaluated the effect of the glycine antagonist, ZD9379, on SDs and brain infarction. Male Sprague-Dawley rats (n = 18) weighing 290 to 340 g undergoing permanent middle cerebral artery occlusion (MCAO) were randomly and blindly assigned to receive drug or placebo: Group 1 (pre-MCAO treatment group, n = 5) a 5 mg/kg bolus of ZD9379 over 5 minutes followed by 5 mg/kg/hour drug infusion for 4 hours beginning 30 minutes before MCAO; Group 2 (post-MCAO treatment group, n = 7) a 5 mg/kg bolus of ZD9379 30 minutes after MCAO followed by 5 mg/kg/hour drug infusion for 4 hours; and Group 3 (control group, n = 6) vehicle for 5 hours beginning 30 minutes before MCAO. SDs were monitored electrophysiologically for 4.5 hours following MCAO by continuous recording of cortical direct current (DC) potentials and electrocorticogram (ECoG). Infarct volume was measured 24 hours after MCAO by 2,3,5 triphenyltetrazolium chloride (TTC) staining. Corrected infarct volume was 90 +/- 72 mm3 (mean +/- standard deviation) in Group 1, 105 +/- 46 mm3 in Group 2, and 226 +/- 41 mm3 in Group 3 (P < .001). The corresponding numbers of SDs in the 3 groups were 8.2 +/- 5.8, 8.1 +/- 2.5, and 16.0 +/- 5.1, respectively (P < .01). When all animals (n = 18) were analyzed, infarct volumes and the number of SDs were significantly correlated (r = .68, P = .002). This study demonstrated that ZD9379 initiated before or after MCAO significantly reduced the number of SDs and infarct volume in a permanent focal ischemia model, implying that ZD9379 is neuroprotective and its neuroprotective effect may be related to inhibiting ischemia-related SDs.

Use of Laser Light Scatter Signals to Study the Effect of a Direct-Current Biased Mesh Screen in a Spray Chamber on Aerosols Generated for Use in Atomic Spectroscopy

A new method that relies on tertiary aerosol laser light scatter signals to alleviate the NaCl chemical matrix effect in inductively coupled plasma atomic emission spectroscopy (ICP-AES) is introduced. The method involves monitoring the laser light scatter signal from the entire tertiary aerosol with a line-shaped laser beam and the plasma off. In this work, the tertiary aerosol laser scatter signal was measured to increase nonlinearly with NaCl concentration. The source of the increased scatter signal is described as originating from Coulomb fission events that droplets with net charge experience while inside the spray chamber. Each droplet in the secondary aerosol that undergoes Coulomb fission introduces ∼ 20 progeny droplets into the aerosol stream. The introduction of progeny droplets to the aerosol stream measured by increased laser light scatter signals coincides with an increase in analyte emission, off-axis, at low viewing heights in an inductively coupled plasma, a characteristic of the easily ionized element chemical matrix effect. It is shown that a direct-current potential applied to a mesh screen positioned inside the spray chamber can coarsely control the transport of droplets with net charge through the spray chamber, by effecting their removal from the aerosol stream. With an appropriate voltage applied to the mesh, the laser scatter signal from the tertiary aerosol from a solution containing 100 mM NaCl can be made similar to the scatter signal from a solution that does not contain NaCl. Under the same conditions, calcium-ion lateral emission signal intensity contour maps in a plasma for the same two solutions become similar within the normal analytical zone in the plasma (2 mm wide, from 13 to 19 mm above the load coil).

Brain metabolic and ionic responses to systemic hypoxia in the newborn dog in vivo

Newborns are less sensitive than adults to hypoxic/ischemic injury. However, research into the mechanism of the newborn's relative resistance to reduced brain oxygen levels is relatively scarce, and the time-scale for the disappearance of resistance is not known. The multiprobe assembly (MPA) has enabled us to examine the resistance of puppies at various ages to hypoxia via continuous, simultaneous, on-line measurement of various ionic, metabolic and electrical parameters from the cerebral cortex. The parameters measured included electrocorticogram (ECoG), direct current (DC) steady state potential, extracellular potassium (K+e) and calcium ion concentrations and intra-mitochondriaI Nicotine amide adenine dinucleotide NADH redox levels. These parameters were measured under various degrees of hypoxia (fraction of inspiration oxygen was between 0-10%) in 6-h-old to 24-week-old puppies fn = 44). Sensitivity to hypoxia increased with age, being expressed in the leakage of potassium ions out of the cells (0.3 ± 0.07 mM in the younger puppies and 3.0± 1.3 mM in the older puppies) following an increase in intra-mitochondrial NADH redox levels. Potassium ion (K+e) leakage was apparently due to depleted energy stores resulting from an impairment in the balance between oxygen supply and demand. Although the overall effect was similar, the kinetics of these changes were much faster in the older puppies. The time to initial increase of extracellular K+e was 2.5 ± 0.1 min in the younger puppies and 0.9± 0.1 min in the older puppies. The time to maximum increase of NADH was 3.2 ±0.2 min in the younger puppies and 1.4 ± 0.1 min in the older puppies. Our results indicate that the older puppies utilize the existing oxygen faster than the younger puppies. It is concluded that the increased resistance of newborn puppies to hypoxia is due to intrinsic properties of the brain itself, like the ability of the membrane to maintain ionic homeostasis. [Neurol Res 1999; 21: 765–770]

Sodium homeostasis in rat hippocampal slices during oxygen and glucose deprivation: role of voltage-sensitive sodium channels

The breakdown in brain ionic homeostasis during energy deprivation (anoxic depolarization [AD]) is intimately linked to neuronal injury. We studied the role of one particular route of Na + influx, voltage-sensitive Na + channels, in the AD induced by O 2 and/or glucose deprivation. We recorded extracellular Na + concentration ([Na +] e) and direct current potential (DCP) in the CA1 stratum pyramidale of hippocampal slices using Na +-selective microelectrodes. Tetrodotoxin (0.1–1 μM) delayed the occurrence of AD and reduced the peak change in both [Na +] e and DCP during AD. However the tetrodotoxin effects were overcome by a concomitant reduction in extracellular glucose during anoxia. We conclude that: (1) the activation of voltage-gated Na + channels is involved in the triggering of AD; (2) there may be a critical level of energy depletion when AD occurs and different mechanisms may underlie AD during hypoxia, compared to O 2 and glucose deprivation.

Breakdown of Calcium Homeostasis in Relation to Tissue Depolarization: Comparison between Gray and White Matter Ischemia

In vitro studies suggest that ischemic injury of cerebral white matter is mediated by nonsynaptic cellular mechanisms, such as Ca2+ entry into axons through reversal of the Na+ -Ca2+ exchanger. The authors investigated extracellular Ca2+ concentration in relation to tissue depolarization (direct current potential) in vivo using ion-selective electrodes in cortical gray and subcortical white matter of alpha-chloralose-anesthetized cats during 120 minutes of global cerebral ischemia. On induction of ischemia, regional CBF, as measured by hydrogen clearance, ceased. The direct current potential decreased rapidly within minutes in gray matter and with little time delay in white matter. Extracellular Ca2+ concentration decreased just as quickly in gray matter. In white matter, in contrast, extracellular Ca2+ increased in the first 20 to 30 minutes, and a delayed and much slower decline, compared with gray matter, was observed thereafter, reaching a minimal level only about 60 minutes after occlusion. Our results suggest that smaller and delayed transmembrane shifts of Ca2+ are correlates of delayed ischemic membrane dysfunction in central white matter tracts, which may be explained by a lack of synaptic mechanisms.