Biomedical subjects

D V Lewis

Publications and source records attributed to D V Lewis.

At least 37 records · Page 2Linked to original sources

PubMed1993

GABAB autoreceptors mediate activity-dependent disinhibition and enhance signal transmission in the dentate gyrus.

1. Activity-dependent depression (fading) of polysynaptic inhibition and the effects of this disinhibition on signal transmission were studied in the dentate gyrus of the rat hippocampal slice with the use of intracellular and extracellular recordings. 2. Polysynaptic inhibitory postsynaptic potentials/currents (IPSP/Cs) were evoked in dentate granule cells by stimulation of mossy fibers in stratum lucidum of area CA3b/c. These mossy fiber-evoked IPSP/Cs consisted of an early GABAA receptor-mediated component (IPSP/CA) and a late GABAB receptor-mediated component (IPSP/CB). 3. When paired stimuli were delivered 200 ms apart under voltage clamp, the amplitude of the IPSCA and IPSCB evoked by the second stimulus was reduced by 37.0 +/- 4.0 and 61.6 +/- 7.8% (mean +/- SE), respectively. Paired-pulse depression of both IPSCA and IPSCB was greatest at interstimulus intervals of 100-400 ms with a maximal effect when stimuli were delivered 200 ms apart. 4. (+/-) Baclofen, a GABAB receptor agonist, suppressed both components of the mossy fiber-evoked IPSP in a concentration-dependent fashion. At a concentration that only partially suppressed the initial IPSP, baclofen occluded paired-pulse depression of IPSPA. In addition, paired-pulse depression of IPSPA was blocked in a concentration-dependent fashion by 2-hydroxy-saclofen (10-400 microM), a GABAB receptor antagonist. 5. The contribution of the IPSPB conductance increase to paired-pulse depression of IPSPA was evaluated. Paired-pulse depression of IPSPA was significantly greater than was the depression of the response to a current pulse delivered 200 ms after the mossy fiber stimulus. In addition, injection of granule cells with GTP gamma S, a nonhydrolyzable guanosine triphosphate (GTP) analogue, occluded both IPSPB as well as the effects of baclofen on the granule cell membrane by activating G proteins but did not reduce paired-pulse depression of IPSPA or suppression of IPSPA by baclofen. Finally, examination of the first and second IPSCA evoked by paired stimuli 200 ms apart revealed no significant differences in response kinetics. Taken together, these results indicate that postsynaptic GABAB receptors on the granule cells are not responsible for paired-pulse depression of IPSPA. 6. Monosynaptic IPSPs were evoked by direct stimulation of inhibitory neurons in the inner molecular layer of the dentate gyrus during pharmacological blockade of excitatory transmission with D(-)-2-amino-5-phosphonovaleric acid (D-APV), an N-methyl-D-aspartate (NMDA) receptor antagonist and 6,7-dinitroquinoxaline-2,3-dione (DNQX), a non-NMDA glutamate receptor antagonist.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗

PubMed1993

Temporal lobe hypometabolism on PET: predictor of seizure control after temporal lobectomy.

To investigate the relationship of temporal lobe hypometabolism demonstrated on PET to surgical outcome and underlying pathology, we reviewed 30 consecutive epilepsy patients who underwent interictal PET studies with 18F fluorodeoxyglucose before temporal lobectomy. Two interpreters blindly reviewed the PET studies and graded them for degree, extent, and location of temporal lobe hypometabolism. Pathologic analysis of en bloc resected tissue showed mesial temporal sclerosis (n = 22), astrocytoma (n = 2), and no pathologic diagnosis (n = 6). Outcome (24 to 40 months' follow-up) was rated as seizure-free (21 patients), significantly improved (five patients), and not significantly improved (four patients). Both the degree and extent of the temporal lobe hypometabolism demonstrated on PET were strongly associated with subsequent seizure control. Pathologic findings, however, did not correlate with degree of PET hypometabolism or subsequent outcome. These data demonstrate that in patients judged to have temporal lobe epilepsy, the presence of temporal lobe hypometabolism is associated with a positive outcome after ipsilateral temporal lobectomy.

Adolescent↗

PubMed1992

Protein synthesis inhibition blocks maintenance but not induction of epileptogenesis in hippocampal slice.

We have been examining the role of protein synthesis in the development and maintenance of spontaneous bursting in the rat hippocampal slice. We used stimulus train induced bursting (STIB) as an in vitro model for epileptogenesis, to study the effects of 3 different protein synthesis inhibitors (cycloheximide, anisomycin, puromycin) on the development of bursting. We report here that none of these inhibitors blocked the induction of bursting, suggesting that protein synthesis is not essential for the development of electrically induced bursting. However, when established spontaneous bursting was examined in the presence of cycloheximide, the duration of the bursting phase was markedly reduced, suggesting that the maintenance of spontaneous bursting in the early hours requires ongoing protein synthesis.

Animals↗

PubMed1992

Mu opioid receptor-mediated modulation of synaptic currents in dentate granule cells of rat hippocampus.

1. The effect of a selective mu opioid agonist, [N-MePhe3-D-Pro4]morphiceptin (PL017), on synaptic transmission in the dentate gyrus was examined in hippocampal slices. Synaptic currents were evoked by stimulation of the outer molecular layer and recorded from granule cells using whole-cell voltage-clamp techniques. 2. Monosynaptic inhibitory postsynaptic currents (IPSCs) were evoked in the presence of D(-)-2-amino-5-phosphonovaleric acid (D-APV), and N-methyl-D-aspartate (NMDA) receptor antagonist, and 6,7-dinitroquinoxaline-2,3-dione (DNQX), a non-NMDA type of glutamate receptor antagonist. The IPSCs consisted of a gamma-aminobutyric acid (GABA)A receptor-mediated early component and a GABAB receptor-mediated late component. 3. Bath application of PL017 (0.3-3 microM) induced a dose-dependent reduction in the amplitude of both early IPSCs (21-56%) and late IPSCs (43-81%). These effects could be reversed by the opiate antagonist naloxone (1 microM) or prevented by the selective mu antagonist beta-funaltrexamine hydrochloride (10 microM). 4. NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) were revealed in the presence of DNQX and the GABAA antagonist bicuculline methiodide. PL017 (3 microM) caused a 35% reduction in the amplitude of NMDA EPSCs. NMDA receptor-mediated population EPSPs recorded extracellularly were also inhibited by 3 microM PL017 to a similar degree. 5. Non-NMDA receptor-mediated EPSCs were demonstrated in the presence of D-APV and bicuculline methiodide. The amplitude of non-NMDA EPSCs was not affected by PL017.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗

PubMed1992

Accuracy and interobserver reliability of scalp ictal EEG.

We studied the accuracy and reliability of scalp ictal EEG in 137 complex partial seizures (119 temporal and 18 extratemporal) in 35 patients in whom we knew the correct site of seizure origin because all patients had been seizure-free for more than 2 years after seizure surgery. Three electroencephalographers independently determined side of seizure origin based on activity at onset of electrographic seizure (ASO), rhythmic theta and alpha (RTA), postictal findings (PIF), and the electrographic seizure as a whole. When all seizures were analyzed, including those with generalized features or obscured by artifact, we determined side of seizure onset correctly in 76% to 83% of temporal seizures and 47% to 65% of extratemporal seizures. In most of the remainder, a lateralization judgment was impossible. When analysis was confined to those seizures in which lateralization was possible, we correctly lateralized 93% to 99% of temporal seizures and 89% to 100% of extratemporal seizures. Interobserver reliability was excellent. RTA and PIF were more accurate than ASO. RTA was significantly more common in temporal seizures. Our data indicate that lateralization by scalp EEG is highly accurate and reliable.

Electroencephalography↗

PubMed1992

Rasmussen's encephalitis: neuroimaging findings in four patients.

Rasmussen's encephalitis is a devastating disease of childhood causing progressive neurologic deficits and intractable seizure activity. Patients frequently have episodes of epilepsia partialis continua and, much less frequently, generalized status epilepticus. The seizures are intractable despite aggressive medical management. In advanced cases, hemispherectomy appears to be the only option to control the seizures. Permanent physical and mental impairments are inevitable. The cause of this disease is unknown, although pathologic specimens demonstrate nonspecific changes that are compatible with viral encephalitis. The progressive brain damage is typically so insidious in onset and gradual in course that it is difficult to make an accurate diagnosis on the basis of clinical evidence. We retrospectively evaluated the CT, xenon CT, positron emission tomographic, and MR neuroimaging findings in four young patients with pathologically suspected Rasmussen's encephalitis (three patients had CT scans, two had xenon CT scans, two had MR scans, and one had a positron emission tomogram). All studies showed abnormalities of the involved cerebral hemisphere: CT and MR revealed nonspecific atrophy, xenon CT showed decreased cerebral blood flow, and positron emission tomography revealed a hypometabolic state. Rasmussen's encephalitis is a diagnosis of exclusion; however, the information obtained from neuroimaging studies in combination with the clinical course should suggest this disorder.

Adolescent↗

PubMed1992

GABAB receptors mediate disinhibition and facilitate long-term potentiation in the dentate gyrus.

We examined the role of synaptic inhibition in regulating the development of long-term potentiation (LTP) in the dentate gyrus of the rat hippocampal slice. LTP was produced by delivering repetitive stimulation to the molecular layer at 5 Hz, a frequency in the range of theta rhythm. During this repetitive stimulation, responses became wider and developed extra population spikes. This enhancement was caused by an increase in the N-methyl-D-aspartate (NMDA) component of the response. NMDA responses became enhanced because there was suppression of the underlying gamma-aminobutyric acid-A (GABAA) receptor-mediated inhibitory postsynaptic potential (IPSP). Application of 2-OH saclofen prevented both the suppression of the IPSP as well as the increase in the NMDA component, demonstrating that the enhancement of the NMDA response was caused by a GABAB receptor-mediated suppression of inhibition. Furthermore, by preventing the GABAB receptor-mediated disinhibition, and thus the increase in the NMDA component, 2-OH saclofen blocked the development of LTP following the stimulus train. These observations indicate that GABAB receptor-mediated disinhibition is required for LTP induction by 5-Hz stimulation, and suggest that GABAB receptors represent a novel site for modulation of synaptic plasticity. The possible functional significance of these phenomena in the intact hippocampal deserves to be investigated.

Afferent Pathways↗

PubMed1991

Facilitation of the induction of long-term potentiation by GABAB receptors.

Long-term potentiation (LTP), an in vitro model of learning, was induced in hippocampal slices by 5-hertz stimulation. During induction, gamma-aminobutyric acid A (GABAA) inhibition decreased, causing the N-methyl-D-aspartate receptor-mediated excitation to increase. 2-OH Saclofen, a GABAB receptor antagonist, prevented the reduction of inhibition, the increase of excitation, and the induction of LTP. Therefore, disinhibition caused by GABAB receptors is required for induction of LTP by 5-hertz stimulation. GABAB receptor modulation of synaptic plasticity occurs at frequencies in the range of the endogenous hippocampal theta rhythm, which has been shown to modulate LTP in vivo.

2-Amino-5-phosphonovalerate↗

PubMed1991

Ethanol and magnesium ions inhibit N-methyl-D-aspartate-mediated synaptic potentials in an interactive manner.

The role of magnesium ions in the inhibitory effect of ethanol on NMDA receptor-mediated population synaptic potentials (pEPSPs) in area CA1 of the hippocampus of the adult rat, was studied. The excitatory amino acid (non-NMDA) receptor antagonist, DNQX and the GABAA channel antagonist, picrotoxin, were used to pharmacologically isolate NMDA-mediated pEPSPs. In the presence of a physiological concentration of magnesium (1.0 mM), ethanol (25-100 mM) inhibited NMDA-mediated pEPSPs, with an apparent EC50 of approximately 50 mM. The ability of ethanol to inhibit NMDA-mediated pEPSPs was reduced when the slices were incubated in the absence of magnesium. Concentrations of ethanol, in the range of 50-200 mM (apparent EC50 100 mM), were required to inhibit NMDA-mediated pEPSPs, in the absence of added magnesium. Combination studies of these two antagonists indicated that the sensitivity of NMDA-mediated pEPSPs to one antagonist was not altered by the presence of the other. This finding suggests that the affinity of each antagonist binding site is not affected by the presence of the other antagonist. In the case of ethanol, its low maximum antagonist efficacy may require larger concentrations of ethanol to inhibit NMDA-mediated pEPSPs, in the absence of other non-competitive antagonists such as magnesium.

Animals↗

PubMed1991

Chronic inflammatory demyelinating polyradiculoneuropathy of childhood: treatment with high-dose intravenous immunoglobulin.

We treated four children with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with high-dose intravenous immunoglobulin (IVIG). All patients received 400 mg/kg of IVIG a day for 5 days during relapses, and one patient received additional periodic infusions of 400 mg/kg. All patients showed excellent recovery of motor strength following each relapse that was treated with IVIG. Compared with plasmapheresis (which was used to treat relapses earlier), recovery of function with IVIG treatments was similar, and in two patients it was superior, to plasmapheresis. There were no side effects with IVIG treatments as compared with plasmapheresis with which two children had infection of central lines with Staphylococcus epidermidis, one had profuse bleeding from accidental extrusion of a central line, and one had multiple episodes of major venous thromboses. High-dose IVIG was a safe and effective adjunctive therapy for childhood CIDP in these four patients.

Child↗

PubMed1991

Opioid-mediated facilitation of long-term potentiation at the lateral perforant path-dentate granule cell synapse.

Opioid effects on the development of long-term potentiation (LTP) were investigated at the lateral perforant path (LPP)-dentate granule cell synapse of the hippocampal slice. High frequency stimuli were delivered to the outer molecular layer of the dentate to tetanize the LPP. Significant LTP was induced in the amplitude of the orthodromic population spike and the slope of the population excitatory postsynaptic potential recorded from the granule cell layer and molecular layer. Bath application of naloxone (0.1-10 microM), an opioid antagonist, induced a dose-dependent reduction in the potentiation of both orthodromic population spike and excitatory postsynaptic potential evoked in the LPP, but not in adjacent medial perforant path. PLO17 ([N-MePhe3-D-Pro4]morphiception; 0.3 or 1 microM), a mu opioid agonist, reduced the threshold for LTP and increased the amount of LTP in the LPP. PLO17 also reduced recurrent inhibition and enhanced an N-methyl-D-aspartate (NMDA) receptor-mediated component in single pulse-evoked field potentials in the LPP. The effects of PLO17 were antagonized by 1 microM naloxone and the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid (100 microM). These findings suggest that endogenous opioids released during high frequency stimulation play an important role in the induction of LTP at the LPP synapses. A mu receptor-mediated disinhibition which increases current flow through NMDA channels may contribute to the opioid enhancement of LTP in the dentate gyrus.

2-Amino-5-phosphonovalerate↗

PubMed1991

GABAB-receptor-mediated inhibition of the N-methyl-D-aspartate component of synaptic transmission in the rat hippocampus.

GABA receptor regulation of NMDA-receptor-mediated synaptic responses was studied in area CA1 of the rat hippocampus using extracellular and intracellular recording techniques. Picrotoxin (PTX) was used to suppress GABAA inhibition and 6,7-dinitroquinoxaline-2,3-dione (DNQX) was used to suppress non-NMDA receptor-mediated responses. In this manner, we were able to avoid the complicating factors caused by potentials induced by other excitatory and inhibitory amino acid receptors. Under these conditions, large NMDA-receptor-mediated EPSPs were observed. When paired stimuli were given at interstimulus intervals from 100 to 400 msec, powerful inhibition of the second response was observed. This inhibition was reversed by the GABAB antagonists phaclofen and 2-hydroxy-saclofen; it was also depressed by removal of Mg2+ from the bath. Examination of non-NMDA receptor-mediated synaptic responses (determined in the presence of D-2-amino-5-phosphonovalerate and PTX) showed no such inhibition, thereby supporting the hypothesis that GABAB inhibition of NMDA EPSPs is postsynaptic. This difference in paired-pulse inhibition of NMDA and non-NMDA EPSPs leads us to conclude that there was no evidence of GABAB-mediated presynaptic inhibition of excitatory transmitter release. Intracellular recordings in the presence of DNQX and PTX revealed a phaclofen-sensitive late IPSP that correlated in time with the period of inhibition of NMDA responses. Taken together, these data suggest that paired-pulse-inhibition of NMDA responses is produced by a GABAB-receptor-mediated hyperpolarization of the postsynaptic membrane, causing an enhanced block of the NMDA channels by Mg2+. Regulation of NMDA-mediated synaptic responses by GABAB receptors constitutes a powerful mechanism for control of a major excitatory system in hippocampal pyramidal cells.

Animals↗

PubMed1990

Reduced sensitivity of the N-methyl-D-aspartate component of synaptic transmission to magnesium in hippocampal slices from immature rats.

This study describes the measurement of N-methyl-D-aspartate (NMDA)-mediated excitatory postsynaptic potentials (EPSPs) of the CA1 subregion of transverse hippocampal slices from immature and adult rats. Our methods permit extracellular measurement of NMDA-mediated depolarizations in the presence of magnesium (Mg2+) ions. In comparison to slices from adult rats (75-90 days old), NMDA EPSPs in hippocampus from immature rats (25-35 days old) were of significantly greater amplitude and were significantly less sensitive to magnesium. It is suggested that developmental plasticity may be related to changes in magnesium regulation of the NMDA channel complex.

Aging↗

PubMed1990

Baclofen facilitates the development of long-term potentiation in the rat dentate gyrus.

The effect of baclofen on the development of long-term potentiation (LTP) in the dentate gyrus was examined. Stimulus trains applied to the perforant path in the presence of baclofen produced significantly more potentiation of the perforant path-evoked response than did similar stimulation in control medium. In addition, baclofen enabled stimulus trains, ordinarily subthreshold for LTP induction, to produce LTP. These results demonstrate that GABAB receptor activation by baclofen makes repetitive stimulation more effective at producing LTP.

Action Potentials↗

PubMed1990

Phaclofen antagonizes post-tetanic disinhibition in the rat dentate gyrus.

Tetanic mossy fiber stimulation transiently reduced recurrent inhibition in the rat dentate gyrus. The post-tetanic depression of inhibition was maximal 200 ms after the tetanus and typically lasted for about 2 s. Phaclofen, a selective gamma-aminobutyric acid-B (GABAB) receptor antagonist, significantly increased the post-tetanic level of inhibition. These results suggest that GABAB receptor activation is important for the development of post tetanic disinhibition. We suggest that GABA released during repetitive firing acts on GABAB receptors on inhibitory interneurons to suppress recurrent inhibition.

Animals↗

PubMed1990

Hippocampal epileptiform activity induced by magnesium-free medium: differences between areas CA1 and CA2-3.

Hippocampal slices, from which the entorhinal cortex had been removed, were exposed to artificial cerebrospinal fluid containing no magnesium (0-Mg ACSF) to elicit interictal bursts (IIBs) and electrographic seizures (EGSs). In 0-Mg ACSF, IIBs and EGSs occurred in both area CA1 and area CA3. The IIBs in CA3 led the IIBs in CA1 by several milliseconds. The epileptiform bursts occurring during the EGSs seemed to have the opposite relationship, with bursts in CA1 leading those in CA3 by several milliseconds. When the connections between CA1 and CA2-3 were cut, the IIBs ceased in CA1 and continued in CA3. To further characterize the local differences in epileptiform activity, totally separate minislices of area CA1 and area CA2-3 were prepared. In the CA2-3 minislices, a few EGSs occurred and thereafter only persistent IIBs prevailed. Conversely, in the CA1 minislices, many spontaneous EGSs occurred for long periods of time and no IIBs were seen. Periodic stimulation of the CA1 minislices triggered IIBs that suppressed the recurrent EGSs. In the hippocampal slice exposed to low magnesium, IIBs originate in CA2-3 and are propagated to CA1, where they can have a suppressant effect on EGSs. Furthermore, unlike IIBs, the bursts making up the EGSs seem to start in CA1 and invade CA2-3.

Action Potentials↗

PubMed1990

Anterior temporal lobectomy for complex partial seizures: evaluation, results, and long-term follow-up in 100 cases.

We report evaluation and results in 100 patients who had undergone anterior temporal lobectomy for intractable complex partial seizures. Average follow-up was 9.0 years (range, 2 to 21 years). In the 2nd postoperative year, 63% were seizure free, 16% were significantly improved, and 21% were considered not significantly improved. Mean number of seizures in the last group was 27% of preoperative levels. Surgical results did not change significantly in subsequent postoperative years; good outcomes tended to persist over the longer term. We also examined the utility of continuous depth electrode monitoring in the evaluation of patients with independent bitemporal interictal epileptiform activity. Despite limited numbers of subjects in this category, there was a trend toward improved surgical outcome when such subjects were evaluated with depth electrodes.

Adolescent↗

PubMed1990

Opioid-induced epileptiform bursting in hippocampal slices: higher susceptibility in ventral than dorsal hippocampus.

The disparity between the seizure sensitivity of the dorsal and ventral hippocampus to opioid peptides was studied by an in vitro electrophysiological method. Slices taken from the ventral (temporal) and dorsal (septal) regions of rat hippocampi were perfused in artificial cerebrospinal fluid bubbled continuously with 95% O2-5% CO2 at 34 degrees C. A stimulating electrode was placed in the stratum radiatum of CA3 region and electrical activity was recorded from the pyramidal cell body layer of the CA3b region. Paired dorsal and ventral hippocampal slices were perfused with [N-Me-Phe3-D-Pro4]morphiceptin (PL017), a specific mu opioid receptor agonist. Application of 0.05 microM PL017 produced triggered and spontaneous bursting in 20% of ventral hippocampal slices, but no such effect was observed in dorsal hippocampal slices. At 0.5 microM PL017, 80% of ventral hippocampal slices developed spontaneous bursting, whereas only 10% of dorsal hippocampal slices had spontaneous bursting. Slices from the ventral hippocampus consistently produced greater degrees of bursting at lower doses relative to the dorsal hippocampus. The addition of 0.1 microM naloxone before or after PL017 inhibited the triggered response but could not block the spontaneous bursting. Perfusion of ACSF for 1 hr also eliminated the triggered response but could only reduce the frequency of the spontaneous bursting. These results suggest that the ventral hippocampus has a higher susceptibility to PL017-induced epileptiform bursting, and this effect is mediated, at least in part, through mu opioid receptors.

Animals↗