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O C Snead

Publications and source records attributed to O C Snead.

At least 19 recordsLinked to original sources
PubMed1992

Evidence for G protein modulation of experimental-generalized absence seizures in rat.

Pertussis toxin is known to inhibit G proteins via ADP-ribosylation, and a response to pertussis toxin is presumptive evidence of G protein modulation of the activity being studied. Therefore, in order to test the hypothesis that G protein-mediated mechanisms are involved in the pathogenesis of generalized absence seizures, the effect of pertussis toxin in two pharmacological models of generalized absence seizures in rat was investigated. The experimental absence seizure models used were the gamma-hydroxybutyrate (GHB) model and low dose pentylenetetrazole (PTZ) model in rat. Pretreatment with pertussis toxin administered intracerebroventricularly (i.c.v.) resulted in a significant decrease in duration of seizure in both models. These data suggest that G-protein-mediated mechanisms may be involved in the pathogenesis of the bilaterally synchronous spike wave discharges (SWD) that characterize experimental absence seizures.

4-Butyrolactone↗
PubMed1992

Ontogenic study of lithium-pilocarpine-induced status epilepticus in rats.

Lithium is known to potentiate the ability of pilocarpine to induce status epilepticus in rats. The goal of this study was to determine whether lithium could potentiate pilocarpine-induced seizures in developing animals. Behavioral, electroencephalographic (EEG), and histopathological changes induced by systemic administration of lithium (3 meq/kg) followed 20 h later by pilocarpine (3, 10, 30, 60 mg/kg) were studied in 3-30-day-old rats. Lithium followed by pilocarpine (30 and 60 mg/kg) induced hyperactivity, tremor, loss of postural control and scratching but no electrographic seizures in 3-8-day-old rats. In the 7-10-day-old animals pretreatment with lithium and pilocarpine 60 mg/kg induced status epilepticus with sustained myoclonus and continuous bilateral synchronous spike and sharp wave, but doses of pilocarpine lower than 60 mg/kg had no effect. The susceptibility to lithium-pilocarpine-induced status epilepticus increased markedly during the third postnatal week of life. During this time period, rats treated with lithium (3 meq/kg) plus pilocarpine 10 mg/kg exhibited behavioral and EEG manifestations of status epilepticus. The same combination of lithium and pilocarpine failed to induce status epilepticus either before or after the third week of life. Histopathological analysis of the brains of the animals used in these studies failed to demonstrate the widespread damage reported in adult rats that have undergone lithium-pilocarpine-induced status epilepticus.

Aging↗
PubMed1992

The GABAA receptor complex in experimental absence seizures in rat: an autoradiographic study.

The regional distribution of radioactive ligand binding for different receptors of the gamma-aminobutyric acid A (GABAA)-benzodiazepine-picrotoxin chloride channel complex was measured on tissue section by autoradiography in brains taken from a genetic strain of Wistar rats with spontaneous absence-like seizures, the genetic absence epilepsy rats from Strasbourg (GAERS), and a control colony. The ligands employed included [3H]muscimol for high affinity GABA agonists sites; [3H]SR 95531 for the low-affinity GABA sites; [3H]flunitrazepam for the benzodiazepine sites; and [35S]t-butyl bicyclophosphorothionate (TBPS) for the picrotoxin site. There was no significant change between GAERS and control animals in [3H]flunitrazepam and [35S]TBPS binding. However, there was significantly decreased [3H]muscimol and [3H]SR 95531 binding in the CA2 region of the hippocampus of the GAERS. This was due to a decrease in Bmax of both [3H]muscimol and [3H]SR 95531 binding in the epileptic strain.

Animals↗
PubMed1992

Evidence for GABAB-mediated mechanisms in experimental generalized absence seizures.

Experimental absence seizures are characterized by the fact that they are exacerbated by both direct and indirect GABA agonists. To date most of the studies that have examined this phenomenon have utilized GABAA agonists. We assessed the effect of a GABAB agonist, baclofen and a specific GABAB antagonist in two pharmacological models of absence seizures in rodent after using either gamma-hydroxybutyrate or pentylenetetrazole to induce the bilaterally synchronous spike wave discharges that typify absence seizures in rodent. Baclofen markedly prolonged and the GABAB antagonist attenuated or blocked the experimental absence seizures in both models. These data suggest a role for GABAB-related mechanisms in the pathogenesis of generalized absence seizures and raise the possibility that GABAB antagonists may have therapeutic potential as antiabsence drugs.

Animals↗
PubMed1992

Corticotropin-releasing hormone-induced seizures in infant rats originate in the amygdala.

The neuroanatomical substrate of seizures induced by picomolar amounts of corticotropin-releasing hormone in infant rats was investigated. Electrographic and behavioral phenomena were monitored in 42 rat pups aged 5 to 22 days. Rat pups carried bipolar electrodes implanted in subcortical limbic structures, as well as cortical electrodes and intracerebroventricular cannulae. The administration of corticotropin-releasing hormone produced age-specific seizures within minutes, which correlated with rhythmic amygdala discharges. Paroxysmal hippocampal and cortical discharges developed subsequently in some rats. Corticotropin-releasing hormone-induced electrographic and behavioral seizures originate in the amygdala.

Aging↗
PubMed1992

Pharmacological models of generalized absence seizures in rodents.

A number of animal models of generalized absence seizures in rodents are described. These include absence seizures induced by gamma-hydroxybutyrate (GHB), low dose pentylenetetrazole, penicillin, THIP, and AY-9944. All of these models share behavioral and EEG similarity to human absence seizures and show pharmacologic specificity for antiabsence drugs such as ethosuximide and trimethadione. Moreover, the absence seizures induced by these agents are exacerbated by GABAergic agonists, a property unique to experimental absence seizures. These models are predictable, reproducible, and easy to standardize. They are useful both in studying mechanisms of pathogenesis of absence seizures as well as in screening for antiabsence activity of potential antiepileptic drugs.

Animals↗
PubMed1992

gamma-Hydroxybutyric acid binding sites: interaction with the GABA-benzodiazepine-picrotoxin receptor complex.

The effect of three compounds known to allosterically modulate binding to the GABA/benzodiazepine/picrotoxin receptor complex on 4-hydroxy-2,3 [3H]butyric acid (GHB) binding was investigated. Pentobarbital, pentylenetetrazole, and picrotoxin enhanced [3H]GHB binding in a dose dependent fashion. Pentobarbital enhanced 4-hydroxy-2,3 [3H]butyric acid binding was associated with an increase in Bmax while pentylenetetrazole and picrotoxin altered the affinity of GHB for its binding site producing a decrease in Kd. These findings suggest that the GHB and GABA receptor complex may share certain moieties in common.

Animals↗
PubMed1992

Involvement of excitatory amino acid mechanisms in gamma-hydroxybutyrate model of generalized absence seizures in rats.

gamma-Hydroxybutyric acid (GHB), a naturally occurring compound which is synthesized from gamma-aminobutyric acid (GABA), induces bilaterally synchronous spike wave discharges, associated with behavioral changes, reminiscent of petit mal or generalized absence seizures in rats. In the present study, possible involvement of excitatory amino acids (EAAs) in GHB-induced spike wave discharges was investigated. The noncompetitive antagonist of NMDA receptors, MK-801, attenuated GHB-induced spike wave discharges at all doses tested (0.025-1.0 mg/kg) but dose-dependently induced suppression of EEG bursts in GHB-treated animals. The suppression of bursts was never observed with GHB in control experiments. N-Methyl-D-aspartate (NMDA) had a similar effect on GHB-induced spike wave discharges, when it was administered prior to GHB. This effect of NMDA was partially reversed by MK-801. The competitive antagonists of NMDA receptors, (+/-)CPP and CGP 43487 and the antagonist at the strychnine-insensitive glycine site, HA-966, also suppressed GHB-induced spike wave discharges with the EEG progressing to suppression of bursts but were weaker in this regard than MK-801 or NMDA. These data raise the possibility of involvement of excitatory amino acids in the GHB model of absence seizures.

Amino Acids↗
PubMed1992

Section of the corpus callosum in kainic acid induced seizures in rats: behavioral, electroencephalographic and neuropathological study.

Clinical and experimental data suggest that the role of corpus callosum in epilepsy includes synchronization, spread, excitation and inhibition. Section of the corpus callosum (SCC) is known to be a useful therapy in selected types of generalized epilepsy, i.e., tonic, atonic and generalized convulsive seizures, but not partial seizures which may be exacerbated by this procedure. The goal of this study was to determine the effect of SCC in the kainic acid (KA) model of limbic seizures in rats. Using several doses of KA (2.5, 5 and 10 mg/kg) injected systemically, we found a potentiation of the behavioral, electrographic and histological effects of KA in the SCC group of animals compared to the sham-operated control rats. A low dose of kainic acid (2.5 and 5 mg/kg) induced status epilepticus in the SCC animals, but not in the sham-operated control rats. These data demonstrate that in the KA model of temporal lobe seizures, SCC not only fails to protect, but actually intensifies seizures. This finding is compatible with the hypothesis that there is an inhibitory influence, via the corpus callosum, of the non epileptic neocortex on its contralateral homologue in the kainic acid model.

Animals↗
PubMed1992

Corpus callosotomy in the lithium-pilocarpine model of seizures and status epilepticus.

Section of the corpus callosum (SCC) is a useful surgical therapy in selected types of epilepsy, i.e., tonic, atonic, and intractable generalized convulsive seizures. Experimentally, the effects of SCC have been documented in animal models of focal seizures as well as generalized seizures. The object of this study was to determine the effect of SCC on behavioral and EEG symptomatology in the lithium-pilocarpine model of seizures and status epilepticus in the rat. SCC was well tolerated. Fifty-seven percent of SCC animals never developed status epilepticus, while all control animals developed status epilepticus. None of the SCC animals died after 24 h but 59% of control animals died within 24 h of status. Histology verified the extent of the SCC and demonstrated widespread brain damage in all animals who exhibited status epilepticus after 72 h. SCC was associated with a lesion of hippocampal commissure in 64% of animals in the SCC group. This protective effect was not related to lesion of the skull or the longitudinal sinus. The lesion of the hippocampal commissure may have contributed to the protective effect of SCC, since animals with an isolated lesion of the hippocampal commissure without SCC survived the status and showed an increased latency to seizure and status epilepticus. These data suggest that the lithium-pilocarpine model of status epilepticus may be useful in the study of the mechanism of efficacy of SCC in the treatment of epilepsy.

Animals↗
PubMed1992

Brain-adrenal axis hormones are altered in the CSF of infants with massive infantile spasms.

Massive infantile spasms (MIS), a seizure disorder unique to infants, is considered an age-dependent response of the immature brain to various insults and stressors. The seizures improve with ACTH and glucocorticoids, both major components of the brain-adrenal axis. We hypothesized that CNS levels of these hormones are abnormal in infants with MIS and studied CSF from 14 infants with MIS and 13 age-matched controls by analysis for corticotropin-releasing hormone (CRH), ACTH, cortisol, and interleukin-1-beta. ACTH levels in CSF of patients were significantly lower than those of controls, but differences in cortisol levels between patients and controls were not statistically significant. CRH levels in both groups were similar and fluctuated diurnally. These results indicate an alteration of specific CNS components of the brain-adrenal axis in MIS.

Adrenocorticotropic Hormone↗
PubMed1979

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PubMed1979

Familial arteriovenous malformation.

A family is reported in which 3 siblings, 2 with the same and the third with a different father, were demonstrated to have cerebral arteriovenous malformations.

Adolescent↗
PubMed1979

Plasma and central nervous system kinetics of gamma-hydroxybutyrate.

Sodium gamma-hydroxybutyrate was administered to dogs in dosages of 200 to 1000 mg per kg with continuous EEG and temperature monitoring. Based on these studies, pulsed doses of 500 mg/kg of GHB were given and timed serum, cerebrospinal fluid (CSF) and brain samples obtained. In addition a group of animals were sacrificed 60 minutes after GHB administration and the regional distribution of GHB determined. The CSF kinetics of GBH suggests a passive diffusionof GHB into CSF but brain concentration peaked very early. Highest concentrations of GHB were found in cortical white matter with lower concentrations in subcortical areas.

Animals↗
PubMed1979

Febrile seizures.

Thirty to 40 percent of children who have a febrile seizure between the ages of six months and six years are at risk for further and more serious febrile seizures and possibly for afebrile seizures. The risk is heightened if the child is less than one year of age and if the seizure lasts more than 20 minutes or is focal rather than generalized. A history of epilepsy in a first-degree relative also increases the risk. The use of long-term phenobarbital therapy is advocated when the seizure is "atypical".

Anticonvulsants↗