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H S Lustig

Publications and source records attributed to H S Lustig.

13 recordsLinked to original sources
PubMed1996

omega-agatoxin IVA and excitotoxicity in cortical neuronal cultures.

Because the P- and Q-type Ca2+ channel antagonist omega-agatoxin IVA inhibits glutamate release, agatoxin-related drugs could have a role in the treatment of excitotoxic neurologic disorders such as stroke. We examined the effect of omega-agatoxin IVA on excitotoxicity (lactate dehydrogenase release) induced by depolarization with veratridine or ouabain, or by N-methyl-D-aspartate, in neuron-enriched cerebral cortical cultures. omega-Agatoxin IVA (< or = 300 nM) failed to reduce excitotoxicity, as did the L-type Ca2+ channel antagonist nimodipine and the N-type antagonist omega-conotoxin GVIA. Drugs that inhibit glutamate release may not necessarily be neuroprotective.

Animals↗
PubMed1994

Pre- and post-synaptic modulators of excitatory neurotransmission: comparative effects on hypoxia/hypoglycemia in cortical cultures.

Neuron-enriched cultures from embryonic rat cerebral cortex were exposed to hypoxia and hypoglycemia, and the resulting cellular injury was quantified by measuring lactate dehydrogenase (LDH) release, which was maximal after 20-24 h. The increase in LDH release produced by hypoxia/hypoglycemia was prevented by N-methyl-D-aspartate (NMDA) antagonists, but not by three classes of drugs thought to modulate glutamate release: Ca2+ channel antagonists (nimodipine, omega-conotoxin GVIA, omega-agatoxin-IVA), KATP channel activators (cromakalim, diazoxide), and glutamate transport inhibitors (dihydrokainate, DL-threo-beta-hydroxyaspartate).

Animals↗
PubMed1994

Enhancement of NMDA toxicity and calcium responses by chronic exposure of cultured cortical neurons to ethanol.

Exposure of rat cerebrocortical cultures to 100 mM ethanol for 3-4 days increased both the neurotoxic potency of N-methyl-D-aspartate (NMDA) and the maximal extent of NMDA-induced intracellular calcium (Ca2+i) elevations. In both control and ethanol-treated cultures, NMDA toxicity correlated closely with [Ca2+]i. Enhancement of NMDA responses may reflect neuronal adaptation to chronic ethanol exposure and could contribute to the pathogenesis of alcohol-related neurologic disorders.

Animals↗
PubMed1993

Calcium indicators and excitotoxicity in cultured cortical neurons.

Membrane-permeating, fluorescent Ca2+ indicators have been used to investigate the role of increased intracellular Ca2+ (Ca2+i) levels in excitotoxic neuronal injury, but their ability to chelate Ca2+i and their own toxic effects in some cells could obscure this relationship. N-Methyl-D-aspartate (NMDA)-stimulated Ca2+i responses and toxicity were measured in neuron-enriched rat cerebrocortical cultures loaded with either fluo-3 or fura-2. Ca2+i responses signaled by both indicators were similar in magnitude, and neither indicator reduced NMDA toxicity, measured by lactate dehydrogenase (LDH) release. Fluo-3 and fura-2 appear to be suitable for comparative studies of NMDA-induced Ca2+i responses and excitotoxicity.

Aniline Compounds↗
PubMed1992

Antiparkinsonian drugs and in vitro excitotoxicity.

N-Methyl-D-aspartate (NMDA) receptor activation has been implicated in the pathogenesis and clinical expression of Parkinson's disease. Because some antiparkinsonian drugs have NMDA antagonist properties, we examined their effects on NMDA toxicity, measured by lactate dehydrogenase (LDH) release, in neuron-enriched cerebrocortical cultures. Amantadine reduced NMDA toxicity with half-maximal reduction at approximately 30 microM, while trihexphenidyl, L-3,4-dihydroxyphenylalanine (L-DOPA), bromocriptine and selegiline were ineffective, and benztropine was itself toxic. Amantadine and related drugs could not only reduce parkinsonian symptoms, but also modify underlying neurodegenerative processes.

Animals↗
PubMed1992

A novel inhibitor of glutamate release reduces excitotoxic injury in vitro.

Excessive release of glutamate has been implicated in the pathogenesis of excitotoxic neurologic disorders, such as stroke. BW 1003C87, an inhibitor of glutamate release and a putative Na+ channel antagonist, reduced veratridine-stimulated, tetrodotoxin- and dizocilpine-sensitive toxicity (measured by lactate dehydrogenase efflux) in neuron-enriched cortical cultures (IC50 = 5 microM). In contrast, BW 1003C87 (300 microM) had no effect on toxicity induced by direct application of 1 mM glutamate or 1 mM N-methyl-D-aspartate, or by depolarization with 50 mM KCl. Glutamate release inhibitors such as BW 1003C87 may provide a novel approach to protection from excitotoxicity.

Animals↗
PubMed1992

Comparative neurotoxic potential of glutamate, endothelins, and platelet-activating factor in cerebral cortical cultures.

The excitatory amino acid glutamate, the peptides endothelin-1 and -3, and the phospholipid platelet-activating factor have been implicated in ischemic injury to the nervous system. To determine if, like glutamate, endothelins and platelet-activating factor are directly toxic to neurons, we examined their effects on lactate dehydrogenase release and trypan blue dye exclusion in rat cerebral cortical cultures. Glutamate (1 mM) increased lactate dehydrogenase release by approximately 75% and reduced the number of cells excluding trypan blue dye by approximately 50%. In contrast, endothelins (0.5 and 100 nM) and platelet-activating factor (0.1 and 10 microM) had no effect on these indices of cell injury. Endothelins and platelet-activating factor appear more likely to act on blood vessels than on neurons or glia as mediators of ischemic injury.

Animals↗
PubMed1992

Cyclic GMP modulators and excitotoxic injury in cerebral cortical cultures.

N-Methyl-D-aspartate (NMDA) receptor activation generates nitric oxide (NO) and cyclic GMP (cGMP) and produces 'excitotoxic' neuronal injury. To examine the possible role of cGMP in excitotoxicity, we evaluated the effects of agents that stimulate or inhibit cGMP activity on the release of lactate dehydrogenase from neuron-enriched cortical cultures. cGMP analogs exhibited no toxicity, and inhibitors of guanylate cyclase or of cGMP-dependent enzymes failed to protect cultures from the toxic effects of NMDA or the NO donor sodium nitroprusside. These findings argue against a role for cGMP in the pathogenesis of excitotoxic neuronal injury.

Animals↗
PubMed1992

Ethanol inhibits excitotoxicity in cerebral cortical cultures.

Excitatory amino acid neurotransmitters have been implicated in the pathogenesis of cerebral ischemia and related forms of acute neuronal injury. Because ethanol inhibits cellular signaling mechanisms activated by excitatory amino acids, we examined its effect on excitatory amino acid-induced toxicity in neuron-enriched cultures prepared from rat cerebral cortex. Both glutamate and N-methyl-D-aspartate (NMDA) were toxic to cultured cortical cells, as demonstrated by a reduction in their ability to exclude trypan blue dye, and this toxicity was reversed by the NMDA antagonist MK-801. Ethanol (100 mM) provided partial protection from the excitotoxic effect of NMDA. Thus ethanol, like conventional excitatory amino acid antagonists, can attenuate excitotoxic neuronal injury in vitro.

Animals↗
PubMed1992

Ethanol and excitotoxicity in cultured cortical neurons: differential sensitivity of N-methyl-D-aspartate and sodium nitroprusside toxicity.

Neural injury due to ischemia and related insults is thought to involve the action of excitatory amino acids at N-methyl-D-aspartate receptors, which results in the influx of extracellular Ca2+ and the generation of nitric oxide. Because ethanol inhibits physiologic responses to excitatory amino acids, we examined its effect on toxicity induced by N-methyl-D-aspartate and by the nitric oxide donor sodium nitroprusside in neuron-enriched cultures prepared from rat cerebral cortex. Both N-methyl-D-aspartate and sodium nitroprusside were cytotoxic, as measured by the release of lactate dehydrogenase and by microfluorescent determination of cell viability. Ethanol (3-1,000 mM) protected cultures from N-methyl-D-aspartate but not sodium nitroprusside toxicity, and the ability of a series of n-alkanols to reproduce the effect of ethanol was related to carbon-chain length. Neuroprotection by ethanol was accompanied by a decrease in the N-methyl-D-aspartate-evoked elevation of free intracellular Ca2+ and did not appear to involve gamma-aminobutyric acid- or cyclic GMP-mediated mechanisms. These findings suggest that ethanol inhibits excitotoxicity at an early step in the N-methyl-D-aspartate signaling pathway, probably by reducing Ca2+ influx, and not by interfering with the action of nitric oxide.

Animals↗
PubMed1978

Participation of house staff in group practice: experience at a tertiary care center.

In order to improve patient care, provide better teaching in an ambulatory setting, and establish research opportunities for faculty staff, the medical clinic of the Children's Hospital of Philadelphia has been developed into a group practice. The entire house staff is involved in this project, and it appears that the endeavor has resulted in improved patient care and house officers who are better prepared for outpatient problems. Some of the difficulties are discussed.

Ambulatory Care↗