PubMed Health⌕ Search

Biomedical subjects

J L Velazquez

Publications and source records attributed to J L Velazquez.

12 recordsLinked to original sources
PubMed2000

Free radical production correlates with cell death in an in vitro model of epilepsy.

Free radical (FR) production, a major step in calcium-dependent neurodegeneration, has been linked to the generation of epileptiform activity and seizure-induced cell death. However, direct evidence of FR production in neurons during seizures has never been presented. Using hippocampal cultured slices we demonstrate that FRs are produced in CA3 but not CA1 pyramidal neurons during the rhythmic synchronous activity induced by the GABAA receptor antagonist bicuculline. The production of FRs (measured as changes in the fluorescence emission of dihydrorhodamine 123) was correlated with an increase in the baseline levels of intracellular calcium ([Ca2+]i) estimated by fluo-3 injected into individual neurons via a patch pipette. [Ca2+]i increased during spike bursting and returned to baseline levels after the burst termination in CA1, but not in CA3, pyramidal neurons where 'interburst' calcium concentrations progressively increased. Measurement of cell death, performed with propidium iodide 48 h after a 30-min exposure to bicuculline, revealed most prominent degeneration of pyramidal neurons in the CA3 pyramidal layer. The FR scavengers vitamin E and glutathione significantly reduced the seizure-induced neurodegeneration without supressing spontaneous epileptiform activity. These observations indicate that FR overproduction is related to seizure-induced neuronal death.

Action Potentials↗
PubMed1999

Type III intermittency in human partial epilepsy.

A rigorous characterization of the dynamic regimes underlying human seizures is needed to understand, and possibly control, the transition to seizure. Intra- or extracranial brain electrical activity was recorded in five patients with partial epilepsy, and the interictal and ictal activity analysed to determine the dynamics of seizures. We constructed first-return one-dimensional maps by fitting the scatter plots of interpeak intervals. The features of the mapping indicated that type III intermittency is the dynamic characteristic of the ictal events. This was confirmed using histograms of the durations of the regular phases during seizures. The intermittent regime explains the abrupt transitions observed during ictal events in terms of transient stabilization of the unstable steady state.

Brain↗
PubMed1999

Synchronization of GABAergic interneuronal networks during seizure-like activity in the rat horizontal hippocampal slice.

We studied the contribution of GABAergic (gamma-aminobutyric acid) neurotransmission to epileptiform activity using the horizontal hippocampal rat brain slice. Seizure-like (ictal) activity was evoked in the CA1 area by applying high-frequency trains (80 Hz for 2 s) to the Schaffer collaterals. Whole-cell recordings from stratum oriens-alveus interneurons revealed burst firing with superimposed high-frequency spiking which was synchronous with field events and pyramidal cell firing during ictal activity. On the other hand, interictal interneuronal bursts were synchronous with large-amplitude inhibitory postsynaptic potentials (IPSPs) in pyramidal cells. Excitatory and inhibitory postsynaptic potentials were simultaneously received by pyramidal neurons during the ictal afterdischarge, and were synchronous with interneuronal bursting and field potential ictal events. The GABAA receptor antagonist bicuculline greatly reduced the duration of the ictal activity in the CA1 layer, and evoked rhythmic interictal synchronous bursting of interneurons and pyramidal cells. With intact GABAergic transmission, interictal field potential events were synchronous with large amplitude IPSPs (9.8 +/- 2.4 mV) in CA1 pyramidal cells, and with interneuronal bursting. Simultaneous dual recordings revealed synchronous IPSPs received by widely separated pyramidal neurons during ictal and interictal periods, indicative of widespread interneuronal firing synchrony throughout the hippocampus. CA3 pyramidal neurons fired in synchrony with interictal field potential events recorded in the CA1 layer, and glutamate receptor antagonists abolished interictal interneuronal firing and synchronous large amplitude IPSPs received by CA1 pyramidal cells. These observations provide evidence that the interneuronal network may be entrained in hyperexcitable states by GABAergic and glutamatergic mechanisms.

2-Amino-5-phosphonovalerate↗
PubMed1999

Bursting in inhibitory interneuronal networks: A role for gap-junctional coupling.

Much work now emphasizes the concept that interneuronal networks play critical roles in generating synchronized, oscillatory behavior. Experimental work has shown that functional inhibitory networks alone can produce synchronized activity, and theoretical work has demonstrated how synchrony could occur in mutually inhibitory networks. Even though gap junctions are known to exist between interneurons, their role is far from clear. We present a mechanism by which synchronized bursting can be produced in a minimal network of mutually inhibitory and gap-junctionally coupled neurons. The bursting relies on the presence of persistent sodium and slowly inactivating potassium currents in the individual neurons. Both GABAA inhibitory currents and gap-junctional coupling are required for stable bursting behavior to be obtained. Typically, the role of gap-junctional coupling is focused on synchronization mechanisms. However, these results suggest that a possible role of gap-junctional coupling may lie in the generation and stabilization of bursting oscillatory behavior.

Action Potentials↗
PubMed1997

Neurotransmitter modulation of gap junctional communication in the rat hippocampus.

Increasing experimental evidence indicates that gap junctions can be modulated by neurotransmitters, in particular dopamine. To examine possible modulation of gap junctional communication in the rat hippocampus by neurotransmitters, we studied dye coupling and electrotonic transmission in the CA1 area in the presence of carbachol, a cholinergic agonist, and dopamine agonists. Carbachol markedly reduced dye coupling and the frequency of electrotonic potentials (spikelets). Spikelet amplitudes were decreased in the presence of carbachol. These effects were reversed by the cholinergic antagonist atropine, suggesting a muscarinic action of carbachol on gap junctional function. The non-specific dopamine agonist apomorphine, and the specific D1 receptor agonist SKF 38393, reduced dye coupling between pyramidal cells. Spikelet frequency was also decreased in the presence of dopamine agonists, but less than with carbachol. The specific D1 receptor antagonist, SCH 23390, reversed the effects of both dopamine agonists. These observations indicate that cholinergic and dopaminergic transmission can affect electrical and chemical (dye coupling) communication through gap junctions, and could therefore alter properties of neuronal assemblies, in addition to their effects on intrinsic membrane properties.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

GABAA receptor immunoreactivity in the white matter.

Using immunohistochemical methods with polyclonal antibodies directed against a specific sequence of the beta 1-subunit of the GABAA receptor, we found strong immunoreactivity in the white matter of cat brain. The immunopositive products were present primarily on processes of glial cells, especially astrocytes. Immunoreactivity appeared also on the cell bodies of astrocytes and on the cytoplasmic membranes of neurons. The abundant immunostaining in the white matter suggests that (1) GABAA receptors are present on glial cells in vivo, (2) GABAA receptors may be localized on non-synaptic membranes in the white matter and (3) activation of GABAA receptors may have some trophic effects on preservation of the structure and functional properties of the white matter.

Amino Acid Sequence↗
PubMed1989

Distribution and lateral mobility of GABA/benzodiazepine receptors on nerve cells.

The distribution and mobility of GABA/benzodiazepine receptors has been examined on living nerve cells by fluorescence digital imaging and fluorescence photobleach recovery with 2 novel fluorescent derivatives of the benzodiazepines Ro7-1986 and 1012S. These fluorescent derivatives retain their high affinity for the GABA/benzodiazepine receptor complex with Ks of 79 and 85 nM, respectively. Digital fluorescence imaging of GABA/benzodiazepine receptors on rat spinal cord neurons maintained in culture reveal that, even in the absence of observable synaptic contact, GABA/benzodiazepine receptors are localized on the cell body in clusters of very high density. Receptor density on processes is lower than on cell bodies, although occasional areas of intense fluorescence were observed. Fluorescence photobleach recovery measurements show that 70% of the GABA/benzodiazepine receptors on the cell body and greater than 85% on the processes of rat spinal cord neurons are immobile. In comparison, voltage-gated sodium channels are diffusely distributed and very mobile on the cell body (D = 10(-9) cm2/sec). The results suggest that even in the absence of nerve-nerve cell contact, there are specific mechanisms that segregate GABA/benzodiazepine receptors to the neuronal cell body and control their lateral mobility.

4-Chloro-7-nitrobenzofurazan↗
PubMed1979

Suxamethonium infusion rate and observed fasciculations. A dose-response study.

Suxamethonium chloride (Sch) was administered i.v. to 36 adult males at six rates: 0.25 mg s-1 to 20 mg s-1. The infusion was discontinued either when there was no muscular response to tetanic stimulation of the ulnar nerve or when Sch 120 mg was exceeded. Six additional patients received a 30-mg i.v. bolus dose. Fasciculations in six areas of the body were scored from 0 to 3 and summated as a total fasciculation score. The times to first fasciculation, twitch suppression and tetanus suppression were inversely related to the infusion rates. Fasciculations in the six areas and the total fasciculation score were related directly to the rate of infusion. Total fasciculation scores in the 30-mg bolus group and the 5-mg s-1 and 20-mg s-1 infusion groups were not significantly different.

Dose-Response Relationship, Drug↗
PubMedDate not supplied

Response time of the Narkotest anesthetic gas monitor.

Response time (RT) of the Narkotest anesthetic gas monitor was measured for 7 inhalation anesthetics, using a 5 L/min fresh gas flow (FGF). Time to 63 percent of maximum response (RT63) and to 95 percent of maximum response (RT95) was directly related to rubber/gas and oil/gas partition coefficients. RT95 ranged from 7 seconds for N2O to 843 seconds for methoxyflurane. RT measured at 0.5 L/min FGF was markedly prolonged over RT at 5 L/min. When the Narkotest was placed on the expiratory limbs of circle-absorber breathing circuits, the difference between the calibrated Narkotest reading (Fn) and the mixed expired circuit concentration (Fc) was shown to depend on the rate of increase of the circuit concentration.

Anesthesia, Inhalation↗