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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new model of status epilepticus (SE), which was induced by intermittent electrical stimulation (20 Hz for 20 sec every min for 180 min) of the deep prepyriform cortex, has been developed in the conscious rat. SE was induced in 9 of 16 rats in the drug-free group. The number of stimulation trains required to induce SE in this status subgroup was 125.6 +/- 12.7 (mean +/- SEM) and the mean duration of self-sustained seizure activity (SSSA) occurring after cessation of the stimulation session was 295.4 +/- 111.4 min. Some animals showed secondary generalized seizures. Significant cell loss was observed in the hippocampal CA3 pyramidal cell layer ipsilateral to the stimulation site and bilateral CA1 areas in the status subgroup compared with the group subjected to sham operation. In addition, there was a significant negative correlation between the duration of SSSA subsequent to the stimulation session and the total number of intact pyramidal neurons observed in the bilateral CA1 and ipsilateral CA3 subfields of the status subgroup. There were significant differences between the status and non-status subgroups with respect to the number of afterdischarges (ADs) and the total AD duration during the stimulation session. Pretreatment with phenobarbital (30 mg/kg) prevented the development of SE and hippocampal cell loss completely. Pretreatment with MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist (0.25 or 1 mg/kg), also prevented hippocampal cell loss, although it did not block SE generation completely, which suggests dissociation of the mechanisms underlying the development of SE and hippocampal damage. These results indicate that prolonged SSSA actually causes hippocampal damage and it is critically dependent upon NMDA receptor participation.
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PMID:Mechanisms in the development of limbic status epilepticus and hippocampal neuron loss: an experimental study in a model of status epilepticus induced by kindling-like electrical stimulation of the deep prepyriform cortex in rats. 153 85

Interneurons from the CA1 lacunosum-moleculare (L-M) region were isolated by trypsin-hyaluronidase treatment and mechanical trituration of the L-M. Interneurons isolated in this manner were multipolar with several dendritic processes and could be distinguished from CA1 pyramidal neurons. The properties of a low-threshold transient (LTT) Ca2+ current were investigated using whole-cell voltage-clamp techniques. The activation threshold of the LTT Ca2+ current was -60 mV, and the peak current, 100 +/- 9 pA (mean +/- SEM; n = 15), was observed at -30 mV. Ca2+ was the predominant charge carrier because the current was not affected by tetrodotoxin and was abolished in Ca(2+)-free external solution. Steady state inactivation was observed when the holding potential was positive to -100 mV, and the current was half-inactivated at -84 mV. Complete inactivation occurred at a holding potential of -60 mV. The time-to-peak of the current was highly voltage dependent and ranged from 10 msec at -60 mV to 4 msec at 0 mV. The time constant of inactivation was also voltage dependent and ranged from 27 msec at -60 mV to 12 msec at greater than -30 mV. Recovery from inactivation to 90% of maximum current occurred within 200 msec. L-M interneurons receive synaptic inputs from the septum that release ACh or GABA and from the raphe nuclei that release 5-HT. Carbachol, a nonhydrolyzable cholinergic agonist, and 5-HT quickly and reversibly increased the amplitude of the LTT Ca2+ current. Carbachol's actions were blocked by atropine, indicating that this effect was mediated by muscarinic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Low-threshold transient calcium current in rat hippocampal lacunosum-moleculare interneurons: kinetics and modulation by neurotransmitters. 167 22

Dendritic function of CA1 pyramidal cells was measured during intracellular recording in vitro and correlated with in vivo behavior in Fischer 344 rats. The aged rats (greater than 26 months) were significantly impaired on a water maze test of hippocampal behavioral function. CA1 neurons from these aged rats demonstrated an elevated action potential threshold compared to the young rats. Electrotonic length (L, in lambda), calculated independently from physiological transients and electrotonic cell reconstructions, was significantly longer in neurons from aged rats (L = 0.73 +/- 0.02 lambda; mean +/- SEM) than in neurons from young rats (L = 0.66 +/- 0.02 lambda). Analysis of proximal and distal synaptic potentials pointed to a more distal electrotonic siting of all dendritic synapses in the aged neurons. Thus, electrical lengthening of dendrites, alterations in synaptic location and decreased excitability in neurons from aged rats with behavioral impairment may represent an endpoint of neuronal reactive mechanisms in response to the aging process.
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PMID:Functional elongation of CA1 hippocampal neurons with aging in Fischer 344 rats. 187 26

Since blockers of excitatory transmission have been shown to reduce anoxic and ischemic neuronal damage, augmentation of inhibitory transmission by agents such as midazolam might have a similar protective effect. Rat hippocampal slices were maintained in vitro and used to determine whether and by what mechanism midazolam improves recovery of evoked responses after anoxia. The Schaffer collateral pathway in the slice was stimulated electrically, and an extracellular potential, the evoked population spike, was recorded from the CA1 pyramidal cells, which are postsynaptic. The slices were made anoxic by substituting artificial cerebrospinal fluid aerated with 95% nitrogen-5% carbon dioxide for fluid aerated with 95% oxygen-5% carbon dioxide. Percentage recovery was expressed as the amplitude of the evoked population spike 60 min after anoxia divided by its preanoxic amplitude. Protection in this model is defined as a significant (P less than 0.05) improvement in percentage recovery compared to the recovery of untreated slices. There was no recovery of the response recorded from CA1 pyramidal cells after 5 min of anoxia (4 +/- 2%) (mean +/- standard error of the mean [SEM]). Slices were treated with midazolam 10 min before, during, and 10 min after anoxia. Midazolam (1 microM) did not enhance recovery after anoxia when dissolved either in water (3 +/- 3%) or in dimethyl sulfoxide (DMSO) (1 +/- 1%). A higher concentration of midazolam (100 microM) did enhance recovery when dissolved in DMSO (27 +/- 7%) but not when dissolved in water (5 +/- 2%). To test whether prolonged pretreatment with midazolam dissolved in water would enhance recovery, slices were treated for 30 min prior to anoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Midazolam improves electrophysiologic recovery after anoxia and reduces the changes in ATP levels and calcium influx during anoxia in the rat hippocampal slice. 204 64

In the present study, we investigated the protective effect of nimodipine against postischemic neuronal damage in the rat and considered the question of whether this histologic finding coincides with an improvement of cerebral circulation. Male Wistar rats were subjected to 10 minutes of forebrain ischemia by clamping both common carotid arteries and lowering blood pressure to 40 mm Hg. Histologic evaluation was performed 7 days after ischemia. Local cerebral blood flow was determined with the 14C-iodoantipyrine technique in anatomically defined areas of the brain, including hippocampus. Preischemic application of nimodipine (3.0 mg/kg p.o.) significantly reduced the percentage of damaged neurons in hippocampal CA1 subfield from 78 +/- 4% in controls to 59 +/- 6% in treated rats (mean +/- SEM; p less than 0.05, Mann-Whitney U test). After 10, 60, and 180 minutes of recirculation no differences in local cerebral blood flow between control and drug-treated animals were observed. Our results demonstrate that nimodipine reduces ischemia-induced neuronal damage in rat hippocampus. We did not consider increased cerebral blood flow in the hypoperfusion state in the applied experimental design since improvement of cerebral blood flow seems to bear little relation to the neuroprotective activity of nimodipine.
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PMID:Neuroprotective effect of nimodipine is not mediated by increased cerebral blood flow after transient forebrain ischemia in rats. 226 Jan 31

(S)-Emopamil is a novel calcium channel blocker of the phenylalkylamine class, with potent serotonin S2 antagonist activity. We investigated the effect of (S)-emopamil on the histopathologic consequences of global brain ischemia in anesthetized rats. Pretreated rats (n = 15) received 20 mg/kg i.p. (S)-emopamil 30 minutes before and 2 hours following 10 minutes of bilateral common carotid artery occlusion plus arterial hypotension (50 mm Hg). Quantitative cell counts following 3 days' survival revealed a marked loss of pyramidal neurons in all subsectors of the hippocampal CA1 area of untreated ischemic rats (n = 15). In contrast, in (S)-emopamil pretreated rats numbers of normal neurons were significantly higher, by 2.4-, 1.9-, and 1.8-fold, respectively, in the medial, middle, and lateral subsectors of the CA1 area. For example, normal neuron counts in the medial CA1 subsector were 34 +/- 9 (mean +/- SEM) in untreated ischemic rats compared with 82 +/- 13 in (S)-emopamil pretreated rats (control nonischemic value [n = 5] 157 +/- 2). By semiquantitative grading, (S)-emopamil also decreased ischemic changes in the cerebral cortex. No significant effect of (S)-emopamil on ischemic injury was detected in rats treated beginning 30 minutes after the ischemic insult (n = 10). Thus, pretreatment with (S)-emopamil is beneficial in decreasing the severity of neuronal injury in global brain ischemia.
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PMID:(S)-emopamil protects against global ischemic brain injury in rats. 226 81

Currents generated by depolarizing voltage pulses were recorded in neurons from the pyramidal cell layer of the CA1 region of rat or guinea pig hippocampus with single electrode voltage-clamp or tight-seal whole-cell voltage-clamp techniques. In neurons in situ in slices, and in dissociated neurons, subtraction of currents generated by identical depolarizing voltage pulses before and after exposure to tetrodotoxin revealed a small, persistent current after the transient current. These currents could also be recorded directly in dissociated neurons in which other ionic currents were effectively suppressed. It was concluded that the persistent current was carried by sodium ions because it was blocked by TTX, decreased in amplitude when extracellular sodium concentration was reduced, and was not blocked by cadmium. The amplitude of the persistent sodium current varied with clamp potential, being detectable at potentials as negative as -70 mV and reaching a maximum at approximately -40 mV. The maximum amplitude at -40 mV in 21 cells in slices was -0.34 +/- 0.05 nA (mean +/- 1 SEM) and -0.21 +/- 0.05 nA in 10 dissociated neurons. Persistent sodium conductance increased sigmoidally with a potential between -70 and -30 mV and could be fitted with the Boltzmann equation, g = gmax/(1 + exp[(V' - V)/k)]). The average gmax was 7.8 +/- 1.1 nS in the 21 neurons in slices and 4.4 +/- 1.6 nS in the 10 dissociated cells that had lost their processes indicating that the channels responsible are probably most densely aggregated on or close to the soma. The half-maximum conductance occurred close to -50 mV, both in neurons in slices and in dissociated neurons, and the slope factor (k) was 5-9 mV. The persistent sodium current was much more resistant to inactivation by depolarization than the transient current and could be recorded at greater than 50% of its normal amplitude when the transient current was completely inactivated. Because the persistent sodium current activates at potentials close to the resting membrane potential and is very resistant to inactivation, it probably plays an important role in the repetitive firing of action potentials caused by prolonged depolarizations such as those that occur during barrages of synaptic inputs into these cells.
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PMID:A voltage-dependent persistent sodium current in mammalian hippocampal neurons. 237

The purpose of our study was to examine whether cyclooxygenase and lipoxygenase inhibitors ameliorate delayed neuronal death in the hippocampal CA1 sector in Mongolian gerbils after 5 minutes of forebrain ischemia. Gerbils were injected intraperitoneally with cyclooxygenase inhibitors piroxicam and flurbiprofen or with lipoxygenase inhibitors AA-861 and BW-755C. Seven days after ischemic insult, the animals were perfusion-fixed, and the neuronal density in the hippocampal CA1 sector was estimated. The average neuronal density in unoperated normal gerbils was 247 +/- 9/mm (mean +/- SEM). In ischemic gerbils with vehicle administration, the average neuronal densities were 13 +/- 2, 14 +/- 2, 13 +/- 2, and 13 +/- 1 for piroxicam, flurbiprofen, AA-861, and BW-755C, respectively. The average neuronal densities in ischemic gerbils treated with 1.5 and 10 mg/kg piroxicam and 1.5 and 10 mg/kg flurbiprofen were 13 +/- 2, 194 +/- 9, 19 +/- 5, and 143 +/- 12, respectively. In ischemic gerbils treated with 15 and 100 mg/kg AA-861 and 30 mg/kg BW-755C, the average neuronal densities were 12 +/- 1, 13 +/- 1, and 14 +/- 2, respectively. At their higher doses, both piroxicam and flurbiprofen significantly (p less than 0.01) ameliorated delayed neuronal death in the hippocampal CA1 sector. Our results suggest that cyclooxygenase products play an important role in the development of delayed neuronal injury after cerebral ischemia.
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PMID:Effect of cyclooxygenase and lipoxygenase inhibitors on delayed neuronal death in the gerbil hippocampus. 250 15

Single unit activity of CA1 and CA3 neurons in the hippocampus was recorded in rats 1, 2, or 3 days after 10 minutes of transient cerebral ischemia induced by the clamping of both carotid arteries combined with hypotension. In addition, paired pulse inhibition/facilitation of the CA1 population spike was examined on Day 2 using two successive stimuli of the contralateral CA3 region delivered at various intervals. On Day 1, the mean +/- SEM firing rate in the CA1 region was 0.91 +/- 0.42/sec (n = 5), which was not significantly different from the control value of 0.98 +/- 0.26/sec (n = 5). Firing rate increased on Days 2 and 3 to 3.96 +/- 0.69/sec (n = 5), and 6.49 +/- 0.89/sec (n = 5), respectively. In the CA3 region, the mean +/- SEM firing rate of 1.18 +/- 0.27/sec in the five control rats sharply dropped to 0.14 +/- 0.11/sec in the five Day 1 rats and gradually increased to 0.45 +/- 0.11/sec in the five Day 3 rats. Histologic examination of these rats revealed ischemic changes restricted to CA1 neurons on Days 2 and 3. The paired-pulse experiment showed no significant difference between six control and six Day 2 rats in the inhibition of the second population spike with interstimulus intervals of less than 400 msec. At interstimulus intervals of greater than 500 msec there was facilitation of the second spike, which lasted 5 seconds in Day 2 rats. This facilitation was not observed in control rats. Because CA3 neurons constitute the main input to CA1 pyramidal cells, decreased activity of CA3 neurons indicates less excitatory input to CA1 neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hippocampal unit activity after transient cerebral ischemia in rats. 254 53

Currents were generated by depolarizing pulses in voltage-clamped, dissociated neurons from the CA1 region of adult guinea pig hippocampus in solutions containing 1 microm tetrodotoxin. When the extracellular potassium concentration was 100 mM, the currents reversed at -8.1 +/- 1.6 mV (n = 5), close to the calculated potassium equilibrium potential of -7 mV. The currents were depressed by 30 mM tetraethylammonium in the extracellular solution but were unaffected by 4-aminopyridine at concentrations of 0.5 or 1 mM. It was concluded that the currents were depolarization-activated potassium currents. Instantaneous current-voltage curves were nonlinear but could be fitted by a Goldman-Hodgkin-Katz equation with PNa/PK = 0.04. Conductance-voltage curves could be described by a Boltzmann-type equation: the average maximum conductance was 65.2 +/- 15.7 nS (n = 9) and the potential at which gK was half-maximal was -4.8 +/- 3.9 mV (mean +/- 1 SEM, n = 10). The relationship between the null potential and the extracellular potassium concentration was nonlinear and could be fitted by a Goldman-Hodgkin-Katz equation with PNa/PK = 0.04. The rising phase of potassium currents and the decay of tail currents could be fitted with exponentials with single time constants that varied with membrane potential. Potassium currents inactivated to a steady level with a time constant of approximately 450 ms that did not vary with potential. The currents were depressed by substituting cobalt or cadmium for extracellular calcium but similar effects were not obtained by substituting magnesium for calcium.
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PMID:Potassium current activated by depolarization of dissociated neurons from adult guinea pig hippocampus. 284 59


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