Mild hypothermia protects rat hippocampal CA1 neurons from irreversible membrane dysfunction induced by experimental ischemia

Onitsuka, Meiko; Mihara, S.; Inokuchi, Hiroe; Shigemori, Minoru; Higashi, Hideho

doi:10.1016/s0168-0102(97)00110-7

Cited by 19 publications

(11 citation statements)

References 38 publications

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“…We also chose to use room temperature as the reversible neuronal depolarization phase is extended under these conditions (Morikawa et al, 1992; Taylor and Weber, 1993). According to the report by Onitsuka et al (1998) the reversible neuronal Vm depolarization phase can last for 14.4 min at 27 °C, which is consistent with our observation that the 15 min. OGD induced electrophysiological changes in hippocampal pyramidal neurons were readily reversible.…”

Section: Discussionsupporting

confidence: 93%

Tamoxifen mediated estrogen receptor activation protects against early impairment of hippocampal neuron excitability in an oxygen/glucose deprivation brain slice ischemia model

Zhang

Xie

Schools³

et al. 2009

Brain Research

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Pretreatment of ovarectomized rats with estrogen shows long-term protection via activation of the estrogen receptor (ER). However, it remains unknown whether activation of the ER can provide protection against early neuronal damage when given acutely, we simulated ischemic conditions by applying oxygen and glucose deprived (OGD) solution to acute male rat hippocampal slices and examined the neuronal electrophysiological changes. Pyramidal neurons and interneurons showed a time-dependent membrane potential depolarization and reduction in evoked action potential frequency and amplitude over a 10 to 15 minute OGD exposure. These changes were largely suppressed by 10 μM TAM. The TAM effect was neuron-specific as the OGD induced astrocytic membrane potential depolarization was not altered. The TAM effect was mediated through ER activation because it could be simulated by 17β-estradiol and was completely inhibited by the ER inhibitor ICI 182, 780, and is therefore an example of TAM’s selective estrogen receptor modulator (SERM) action. We further show that TAM effects on OGD- induced impairment of neuronal excitability was largely due to activation of neuroprotective BK channels, as the TAM effect was markedly attenuated by the BK channel inhibitor paxilline at10 μM. TAM also significantly reduced the frequency and amplitude of AMPA receptor mediated spontaneous excitatory postsynaptic currents (sEPSCs) in pyramidal neurons which is an early consequence of OGD. Altogether, this study demonstrates that both 17β-estradiol and TAM attenuate neuronal excitability impairment early on in simulated ischemia model via ER activation mediated potentiation of BK K+ channels and reduction in enhanced neuronal AMPA/NMDA receptor-mediated excitotoxicity.

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Section: Discussionsupporting

confidence: 93%

Tamoxifen mediated estrogen receptor activation protects against early impairment of hippocampal neuron excitability in an oxygen/glucose deprivation brain slice ischemia model

Zhang

Xie

Schools³

et al. 2009

Brain Research

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“…Hypothermia improves the recovery of resting and action potentials after hypoxia, while hyperthermia decreases the recovery of these potentials. These results agree with those from other animal models of hypoxia and ischemia (Busto et al 1987(Busto et al , 1989aOnitsuka et al 1998a;Rosen and Morris 1994) and with clinical studies, which indicate that mild hypothermia improves and hyperthermia degrades the neurological outcome in patients with ischemic brain injury (Wass and Lanier 1996).…”

Section: Intracellular Ca 2ϩ Concentrationsupporting

confidence: 90%

Differential Fall in ATP Accounts for Effects of Temperature on Hypoxic Damage in Rat Hippocampal Slices

Wang¹,

Chambers²,

Cottrell³

et al. 2000

Journal of Neurophysiology

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Intracellular recordings, ATP and cytosolic calcium measurements from CA1 pyramidal cells in rat hippocampal slices were used to examine the mechanisms by which temperature alters hypoxic damage. Hypothermia (34 degrees C) preserved ATP (1.7 vs. 0.8 nM/mg) and improved electrophysiologic recovery of the CA1 neurons after hypoxia; 58% of the neurons subjected to 10 min of hypoxia (34 degrees C) recovered their resting and action potentials, while none of the neurons at 37 degrees C recovered. Increasing the glucose concentration from 4 to 6 mM during normothermic hypoxia improved ATP (1.3 vs. 0.8 nM/mg) and mimicked the effects of hypothermia; 67% of the neurons recovered their resting and action potentials. Hypothermia attenuated the membrane potential changes and the increase in intracellular Ca(2+) (212 vs. 384 nM) induced by hypoxia. Changing the glucose concentration in the artificial cerebrospinal fluid primarily affects ATP levels during hypoxia. Decreasing the glucose concentration from 4 to 2 mM during hypothermic hypoxia worsened ATP, cytosolic Ca(2+), and electrophysiologic recovery. Ten percent of the neurons subjected to 4 min of hypoxia at 40 degrees C recovered their resting and action potentials; this compared with 60% of the neurons subjected to 4 min of normothermic hypoxia. None of the neurons subjected to 10 min of hypoxia at 40 degrees C recovered their resting and action potentials. Hyperthermia (40 degrees C) worsens the electrophysiologic changes and induced a greater increase in intracellular Ca(2+) (538 vs. 384 nM) during hypoxia. Increasing the glucose concentration from 4 to 8 mM during 10 min of hyperthermic hypoxia improved ATP (1.4 vs. 0.6 nM/mg), Ca(2+) (267 vs. 538 nM), and electrophysiologic recovery (90 vs. 0%). Our results indicate that the changes in electrophysiologic recovery with temperature are primarily due to changes in ATP and that the changes in depolarization and Ca(2+) are secondary to these ATP changes. Both primary and secondary changes are important for explaining the improved electrophysiologic recovery with hypothermia.

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“…Transverse hippocampal slices (450-500 m) were prepared from juvenile (postnatal days [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] and adult (>30 days old) Sprague-Dawley rats (n ‫ס‬ 21). Rats were anesthetized with halothane and then decapitated.…”

Section: Methodsmentioning

confidence: 99%

“…Several mechanisms have been offered to explain the anticonvulsant effect of cortical cooling (11,17,29,30) including reduction of transmitter release, alteration of activation-inactivation kinetics of voltage-gated ion channels, mitigation of effects of hypoxia, and a slowing of catabolic processes. However, the mechanisms by which cooling consistently blocked posttetanic oscillations in our experiments are unknown.…”

Section: Cooling Blocks Posttetanic Oscillation and Clonic Burstsmentioning

confidence: 99%

Cooling Abolishes Neuronal Network Synchronization in Rat Hippocampal Slices

et al. 2002

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Summary:Purpose: We sought to determine whether cooling brain tissue from 34 to 21°C could abolish tetany-induced neuronal network synchronization (gamma oscillations) without blocking normal synaptic transmission.Methods: Intracellular and extracellular electrodes recorded activity in transverse hippocampal slices (450-500 m) from Sprague-Dawley male rats, maintained in an air-fluid interface chamber. Gamma oscillations were evoked by afferent stimulation at 100 Hz for 200 ms. Baseline temperature in the recording chamber was 34°C, reduced to 21°C within 20 min.Results: Suprathreshold tetanic stimuli evoked membrane potential oscillations in the 40-Hz frequency range (n ‫ס‬ 21). Gamma oscillations induced by tetanic stimulation were blocked by bicuculline, a ␥-aminobutyric acid (GABA) Areceptor antagonist. Cooling from 34 to 21°C reversibly abolished gamma oscillations in all slices tested. Short, lowfrequency discharges persisted after cooling in six of 14 slices.Single-pulse-evoked potentials, however, were preserved after cooling in all cases. Latency between stimulus and onset of gamma oscillation was increased with cooling. Frequency of oscillation was correlated with chamber cooling temperature (r ‫ס‬ 0.77). Tetanic stimulation at high intensity elicited not only gamma oscillation, but also epileptiform bursts. Cooling dramatically attenuated gamma oscillation and abolished epileptiform bursts in a reversible manner.Conclusions: Tetany-induced neuronal network synchronization by GABA A -sensitive gamma oscillations is abolished reversibly by cooling to temperatures that do not block excitatory synaptic transmission. Cooling also suppresses transition from gamma oscillation to ictal bursting at higher stimulus intensities. These findings suggest that cooling may disrupt network synchrony necessary for epileptiform activity. Key Words: Epilepsy-Hippocampus-Cooling-HypothermiaSynchronization.Focal cooling has been suggested as a treatment for epilepsy. In vivo experiments confirmed that cooling reversibly inactivates mammalian cortex (1-4). Clinical case reports have documented use of cooling in a variety of epileptic conditions (5-10). Recent studies in hippocampal slices and in whole rats showed that rapid cooling to 22.0°C can halt seizure activity induced by 4-aminopyridine (11,36). Rapid cooling also blocked single-pulsed-evoked potentials in dentate granule cell layer neurons.Mechanisms of cooling as an antiepileptic therapy remain unknown. Tetany-induced discharges in the range of 30-120 Hz, also called gamma oscillations, resemble spontaneous oscillations seen under a variety of epileptic conditions (12). These oscillations reflect network synchronization mediated by ␥-aminobutyric acid (GABA) A -ergic depolarizations. Gamma oscillations recently have been identified in vitro in slice models of epilepsy. They are seen in transition to epileptiform bursting, spontaneously and in response to single-pulse stimulation in low-Mg 2+ conditions, after high-frequency tetanic stimulation, and in juvenile slic...

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Mild hypothermia protects rat hippocampal CA1 neurons from irreversible membrane dysfunction induced by experimental ischemia

Cited by 19 publications

References 38 publications

Tamoxifen mediated estrogen receptor activation protects against early impairment of hippocampal neuron excitability in an oxygen/glucose deprivation brain slice ischemia model

Tamoxifen mediated estrogen receptor activation protects against early impairment of hippocampal neuron excitability in an oxygen/glucose deprivation brain slice ischemia model

Differential Fall in ATP Accounts for Effects of Temperature on Hypoxic Damage in Rat Hippocampal Slices

Cooling Abolishes Neuronal Network Synchronization in Rat Hippocampal Slices

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