The present research examined the hypothesis that omega-3 polyunsaturated fatty acids would increase seizure threshold in rats in vivo, and reduce neuronal excitability in mouse hippocampal slices. Seizure thresholds were measured in rats using the maximal pentylenetetrazol and electrical stimulation seizure tests following α-linolenic acid (ALA) or docosahexaenoic acid administration. ALA raised seizure threshold in the maximal PTZ seizure test, but this effect probably occurred because ALA displaced DHA from liver to the brain. DHA itself was therefore tested in the PTZ and electrical stimulation seizure tests. Direct administration of DHA by subcutaneous injection raised seizure thresholds in the PTZ seizure test, which models tonic-clonic attacks in humans. Dietary enrichment with DHA raised afterdischarge seizure thresholds in the cortex and amygdala, which model simplex and complex partial seizures in humans, although this effect took some time to occur. In vitro, the application of DHA also reduced the incidence of excitatory sharp waves in mouse hippocampal slices. This effect did not appear to be due to either an increase in GABAergic inhibitory tone, nor to a decrease in glutamatergic drive. The fatty acid composition of phospholipids and unesterified fatty acids were measured in the brain following microwave fixation in order to determine whether the effects of DHA on seizure thresholds were due to its de-esterification from the phospholipid membrane. The assay surprisingly revealed that subcutaneous administration of DHA at a dose that raised seizure threshold, increased unesterified arachidonic acid, but not unesterified DHA concentrations during seizures. The results of these studies support the hypothesis that DHA raises seizure threshold in rats, and reduces neuronal excitability in vitro. The effects of DHA on seizure threshold are possibly mediated by the de-esterification of arachidonic acid, which is known to have effects on the voltage-dependent sodium channel.

Thesis (M.Sc.). / Written for the School of Computer Science. Title from title page of PDF (viewed 2008/05/30). Includes bibliographical references.

Thesis (Ed. D.)--University of Missouri-Columbia, 2000. / Typescript. Vita. Includes bibliographical references (leaves 252-255). Also available on the Internet.

Thesis (M.Soc.Sc.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 107-111) Also available in print.

Thesis (Ed. D.)--University of Missouri-Columbia, 2000. / Typescript. Vita. Includes bibliographical references (leaves 252-255). Also available on the Internet.

abstract: Alexithymia is a personality trait characterized by a diminished ability to identify and describe feelings, as well as an inability to distinguish physical symptoms associated with emotional arousal. Alexithymia is elevated in both patients with epilepsy (a neurologically-based seizure disorder) and psychogenic nonepileptic seizures (PNES; a psychological condition mimicking epilepsy); however, different neuropsychological processes may underlie this deficit in the two groups. To expand on previous research considering factors contributing to alexithymia in these populations, we examined the extent to which scores on the Toronto Alexithymia Scale (TAS-20) were predicted by performance on measures of executive and language functioning. We studied 138 PNES and 150 epilepsy patients with video-EEG confirmed diagnoses. Neuropsychological tests were administered to assess executive functioning (interference scores of the Stroop Color-Word Test and Part B of the Trail Making Test) and language functioning (Animals, Controlled Oral Word Association Test, and Boston Naming Test). Hierarchical linear regressions revealed that the relationships between disparate neuropsychological domains and alexithymia were not moderated by diagnosis of PNES or epilepsy. Multiple regression analyses within each group demonstrated that phonemic verbal fluency and response inhibition were significant predictors of alexithymia in epilepsy. Thus, alexithymia may reflect impairments in language and aspects of executive functioning in both PNES and epilepsy. / Dissertation/Thesis / Masters Thesis Psychology 2017

abstract: When surgical resection becomes necessary to alleviate a patient's epileptiform activity, that patient is monitored by video synchronized with electrocorticography (ECoG) to determine the type and location of seizure focus. This provides a unique opportunity for researchers to gather neurophysiological data with high temporal and spatial resolution; these data are assessed prior to surgical resection to ensure the preservation of the patient's quality of life, e.g. avoid the removal of brain tissue required for speech processing. Currently considered the "gold standard" for the mapping of cortex, electrical cortical stimulation (ECS) involves the systematic activation of pairs of electrodes to localize functionally specific brain regions. This method has distinct limitations, which often includes pain experienced by the patient. Even in the best cases, the technique suffers from subjective assessments on the parts of both patients and physicians, and high inter- and intra-observer variability. Recent advances have been made as researchers have reported the localization of language areas through several signal processing methodologies, all necessitating patient participation in a controlled experiment. The development of a quantification tool to localize speech areas in which a patient is engaged in an unconstrained interpersonal conversation would eliminate the dependence of biased patient and reviewer input, as well as unnecessary discomfort to the patient. Post-hoc ECoG data were gathered from five patients with intractable epilepsy while each was engaged in a conversation with family members or clinicians. After the data were separated into different speech conditions, the power of each was compared to baseline to determine statistically significant activated electrodes. The results of several analytical methods are presented here. The algorithms did not yield language-specific areas exclusively, as broad activation of statistically significant electrodes was apparent across cortical areas. For one patient, 15 adjacent contacts along superior temporal gyrus (STG) and posterior part of the temporal lobe were determined language-significant through a controlled experiment. The task involved a patient lying in bed listening to repeated words, and yielded statistically significant activations that aligned with those of clinical evaluation. The results of this study do not support the hypothesis that unconstrained conversation may be used to localize areas required for receptive and productive speech, yet suggests a simple listening task may be an adequate alternative to direct cortical stimulation. / Dissertation/Thesis / M.S. Bioengineering 2013

nÃo hà / O gÃnero Aniba destaca-se por suas propriedades farmacolÃgicas, tais como ansiolÃtica, antidepressiva e vasorelaxante. Dos frutos de Aniba panurensis conhecida popularmente por âlouro amareloâ foi identificada uma pirona natural, a 6-[(E)-esteril-piran-2-ona]. O objetivo do presente trabalho foi verificar os efeitos neurofarmacolÃgicos da 6-[(E)-esteril-piran-2-ona (STY) obtida da Aniba parusinensi em camundongos atravÃs de testes comportamentais (atividade locomotora espontÃnea (ALE), rearing e grooming), testes de induÃÃo de convulsÃo quÃmica e dosagens neuroquÃmicas de aminoÃcidos (glutamato (GLU), aspartato (ASP), Ãcido γ-aminobutÃrico (GABA), glicina (GLI), taurina (TAU), histidina (HIS) em cÃrtex prÃ-frontal (CPF), hipocampo (HC) e corpo estriado (CE). Foram utilizados camundongos Swiss, machos, com peso mÃdio de 28 gramas. Os animais foram tratados com dose Ãnica de STY (1, 5, 10 ou 20 mg) por via intraperitoneal. Trinta minutos apÃs administraÃÃo os animais foram submetidos aos testes comportamentais e teste de convulsÃo induzidas por pentilenotetrazol (PTZ), estricnina, bicuculina e pilocarpina. Imediatamente apÃs os testes os animais foram sacrificados e as Ãreas cerebrais de interesse dissecadas para a dosagem da concentraÃÃo de aminoÃcidos atravÃs de HPLC (High Perfomance Liquid Chromatography). No teste de ALE a STY na dose de 10 ou 20 mg/kg aumentou atividade locomotora quando comparada ao grupo controle. No Labirinto em cruz elevada e o teste da placa perfurada, a STY em todas as doses comprovou seu efeito ansiolÃtico, pois aumentou todos os parÃmetros analisados. Na dosagem de aminoÃcidos neurotransmissores apÃs o teste de comportamento houve aumento nas concentraÃÃes dos aminoÃcidos inibitÃrios (GABA, GLI, TAU, HIS) e excitatÃrios (ASP, GLU) no CPF, HC e CE. ApÃs o prÃ-tratamento com STY os animais foram submetidos ao teste de induÃÃo de convulsÃo por PTZ (85 mg/kg) ou Bicuculina (12 mg/kg) foram observados aumentos na latÃncia de convulsÃo e morte, com animais sobreviventes na maior dose. No teste com a induÃÃo de convulsÃo por estricnina (20 mg/kg/ ocorreu o aumento na latÃncia de convulsÃo (STY-10: 50,42  7,20; STY-20: 65,99  3,22) e latÃncia de morte (STY-1: 20  1,72; STY-10: 19,17  1,87; STY-20: 23,83  1,55) em todos os animais prÃ-tratados com STY. Na induÃÃo de convulsÃo por pilocarpina ocorreu uma diminuiÃÃo da latÃncia de morte. ApÃs os testes os animais realizou-se a dosagem da concentraÃÃo dos aminoÃcidos (ASP, GLU, GLI, TAU e GABA). No CPF aumentaram ASP, TAU, GABA. Jà no HC o aumentou GLU, ASP, GLI e GABA. Na induÃÃo de convulsÃo com estricnina no CPF ocorreu o aumento no ASP, TAU, GABA, enquanto no HC aumentou ASP, GLI, TAU, GABA. No modelo de induÃÃo com bicuculina no CPF aumentou o ASP, GLU, GLI, TAU, GABA, enquanto no HC aumentou ASP, GLU, GLI, TAU, GABA. No modelo de induÃÃo com pilocarpina no CPF aumentou ASP, GABA, GLI, enquanto no HC aumentou apenas o ASP. Conclui-se que a STY apresenta um efeito ansiolÃtico nos testes de comportamento, efeito protetor nos teste de induÃÃo de convulsÃo por PTZ, estricnina e bicuculina. ApÃs o doseamento dos aminoÃcidos pode-se demonstrar a participaÃÃo dos sistemas glutamatÃrgico, GABAÃrgico e glinÃrgico. / The genus Aniba stands out for its pharmacological properties, such as anxiolytic, antidepressant and vasorelaxant. Of the Aniba panurensis fruits popularly known as ―louro amarelo‖ a natural pyrone, 6-[(E)-styryl-pyran-2-one], was identified. The objective of this study was to verify the neuropharmacological effects of 6-[(E)-styryl-pyran-2-one] (STY), obtained from Aniba panurensis, in mice through behavioral tests (spontaneous locomotor activity (SLA), rearing and grooming), tests of chemically induced seizures and neurochemical dosages of amino acids (glutamate (GLU), aspartate (ASP), γ-aminobutyric acid (GABA), glycine (GLY), taurine (Tau), histidine (HIS) in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST). We used Swiss mice, male, with an average weight of 28 grams. The animals were treated with a single dose of STY (1, 5, 10 or 20 mg) by intraperitoneal injection. Thirty minutes after administration, the animals were subjected to behavioral tests of chemically induced seizures by pentylenetetrazol (PTZ), strychnine, bicuculline and pilocarpine. Immediately after the tests, the animals were sacrificed and the brain areas of interest were dissected to estimate the amino acid concentration via HPLC (High Performance Liquid Chromatography). In the SLA test the STY at 10 or 20 mg/kg dose increased locomotor activity when compared to the control group. In the elevated plus-maze and hole-board tests, the STY in all doses proved its anxiolytic effect, because it increased all parameters analyzed. In the dosage of amino acid neurotransmitters after behavioral test there was an increase in inhibitory amino acid concentrations (GABA, GLY, TAU, HIS) and excitatory (ASP, GLU) in PFC, HC and ST. After pretreatment with STY, the animals were tested for seizures induced by PTZ (85 mg/kg) or Bicuculline (12 mg/kg), we observed an increase in the latency of seizures and death in surviving animals at the highest dose. During the strychnine-induced seizures test (20 mg/kg) there was an increase in seizure latency (STY-10: 50.42  7.20; STY-20: 65.99  3.22) and latency to death (STY-1: 20  1.72; STY-10: 19.17  1.87; STY-20: 23.83  1.55) in all animals pretreated with STY. In the pilocarpine-induced seizures there was a decrease in the latency to death. After testing the animals, we conducted the dosage of amino acid concentrations (ASP, GLU, GLY, TAU and GABA). PFC increased ASP, TAU and GABA. HC increased GLU, ASP, GLY and GABA. In the strychnine-induced seizure in PFC there was an increase in ASP, TAU and GABA, while the HC increased ASP, GLY, TAU and GABA. In the bicuculline-induced seizure in PFC there was an increase in ASP, GLU, GLY, TAU and GABA, while the HC increased ASP, GLU, GLY, TAU and GABA. In the pilocarpine-induced seizure in PFC there was an increase in ASP, GABA, GLY, while the HC increased only ASP. We concluded that STY presents an anxiolytic effect in behavioral tests and a protective effect in tests of induced seizures by PTZ, strychnine and bicuculline. After the dosage of the amino acids we can demonstrate the involvement of glutamatergic, GABAergic and glycinergic systems.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Levetiracetam (LEV) is a new antiepileptic drug effective as adjunctive therapy for partial seizures and in experimental models of seizures, including pilocarpine-induced seizures in rodents. Objectifying to clarify if anticonvulsant activity of LEV occurs near cholinergic muscarinic alterations, adult male mice received LEV injections before muscarinic agonistsâ administration. Pretreatment with LEV (30, 50, 100 or 200 mg/Kg, i.p.) increased the latency of seizures, latency of status epilepticus and latency of death on the seizure model induced by pilocarpine, 400 mg/Kg, s.c. (P400). LEV (200 mg/Kg, i.p., LEV200) pretreatment abolished seizures in 53% (20/38) of the animals; reduced status epilepticus appearance in 58% (22/38); increased deathâs latency in 116% compared to P400 group; protected 61% (23/38) of the animals from death and also reduced the intensity of tremors induced by oxotremorine (0,5 mg/kg, i.p). [3H]-N-methylscopolamine binding assays in mice hippocampus showed that LEV200 pretreatment reverts the downregulation on muscarinic acetylcholine receptors (mAChR), induced by P400 administration, bringing back these density values to control ones (0,9% NaCl, i.p.). However, subtype-specific binding assays revealed that P400 and LEV200 alone treatments results in M1 and M2 subtypes decrease, respectively. The agonist-like behavior of LEV200 on the inhibitory M2 mAChR subtype, observed in this work, could contribute to explain the reduction on oxotremorine-induced tremors and the delay on pilocarpine-induced seizures, by an increase in the attenuation of neuronal activity mediated by the M1 receptors. [3H]-spiroperidol binding assays also showed a downregulation of dopaminergic D2 receptors, induced by LEV200 alone treatment. Although this effect was reverted on P400 presence, maybe it posses some influence on LEV200 protective effect, since the stimulation of these receptors can reduce the intensity of pilocarpine induced-seizures. Objectifying to investigate if LEVâ mechanism of action also involves anti-oxidant proprieties, neurochemical analysis were carried out in hippocampus and striatum and showed that P400 produced an increased lipid peroxidation in hippocampus, main epileptogenic focus on cholinergic agents induced-seizures, demonstrating and confirming the involvement of free radical oxygen injury in the P400 induced brain injury. However, LEV200 pretreatment abolished this increase, bringing lipid peroxidation levels back to normal values, suggesting an anti-oxidative property of LEV. Our finds also showed a decrease of nitrite levels and stabilization of catalase activity in hippocampus and striatum, beyond an increase on reduced glutathione levels on hippocampus, induced by LEV200 treatment before P400 administration. In this way, the anti-oxidative action of LEV was showed in several stages involved on oxidative injury, suggesting a novel mechanism of its protector effects. / O levetiracetam (LEV) à uma nova droga antiepilÃptica, com eficÃcia na terapia adicional das convulsÃes parciais e em vÃrios modelos experimentais de convulsÃo, inclusive nas convulsÃes induzidas por pilocarpina em roedores. Objetivando investigar se o mecanismo de aÃÃo anticonvulsivante do LEV està relacionado a alteraÃÃes no sistema colinÃrgico muscarÃnico, camundongos machos adultos receberam injeÃÃes de LEV uma hora antes da administraÃÃo de agonistas muscarÃnicos. O prÃ-tratamento com LEV (30, 50, 100 ou 200 mg/Kg, i.p.) aumentou significativamente as latÃncias de convulsÃo, de estatus epilepticus e de morte no modelo de convulsÃes induzidas por pilocarpina, 400 mg/Kg, s.c. (P400). O prÃ-tratamento com LEV (200 mg/Kg, i.p., LEV200) levou à ausÃncia de convulsÃes em 53% (20/38) dos animais; reduziu a ocorrÃncia de estatus epilepticus em 58% (22/38); aumentou a latÃncia de morte em 116% comparada ao grupo P400; protegeu 61% (23/38) dos animais da morte e, ainda, reduziu a intensidade dos tremores induzidos por oxotremorina (0,5 mg/kg, i.p). Ensaios de binding com [3H]-N-metilescopolamina em hipocampo mostraram que o prÃ-tratamento com LEV200 reverte a downregulation dos receptores muscarÃnicos de acetilcolina, induzida por P400, normalizando a densidade desses receptores. Todavia, ensaios para subtipos especÃficos de receptores muscarÃnicos revelaram que a administraÃÃo de P400 ou LEV200, isoladamente, resulta em downregulation dos subtipos M1 e M2, respectivamente. A aÃÃo agonista-sÃmile do LEV nos receptores prÃ-sinÃpticos inibitÃrios M2, observada no presente estudo, poderia contribuir para explicar a reduÃÃo nos tremores induzidos por oxotremorina e o retardo na instalaÃÃo das convulsÃes induzidas por P400, atravÃs da atenuaÃÃo da atividade neuronal mediada pelos receptores M1. Ensaios de binding com [3H]-espiroperidol demonstraram uma downregulation dos receptores dopaminÃrgicos D2, induzida pela administraÃÃo isolada de LEV200. Embora esse efeito tenha sido revertido na presenÃa de P400, talvez possua alguma influÃncia na aÃÃo protetora oferecida por LEV200, considerando que a estimulaÃÃo desses receptores reduz a intensidade das convulsÃes induzidas pela pilocarpina. Objetivando investigar se o efeito protetor demonstrado pelo LEV envolve propriedades antioxidantes, anÃlises neuroquÃmicas foram realizadas em hipocampo e corpo estriado. A administraÃÃo de P400 aumentou a ocorrÃncia de peroxidaÃÃo lipÃdica no hipocampo, considerado principal foco de instalaÃÃo das convulsÃes provocadas por agentes colinÃrgicos, demonstrando e confirmando o envolvimento de espÃcies deletÃrias na injÃria cerebral produzida por esse modelo de convulsÃes. O prÃ-tratamento com LEV200 reverteu esse efeito, fornecendo indÃcios de uma atividade antioxidante dessa droga. Nossos estudos tambÃm mostraram uma diminuiÃÃo da produÃÃo de nitrito e estabilizaÃÃo da atividade da catalase no hipocampo e corpo estriado e o aumento dos nÃveis de glutationa reduzida no hipocampo, decorrentes do tratamento com LEV antes de P400. A aÃÃo antioxidante do LEV foi evidenciada em vÃrias etapas envolvidas no processo de dano oxidativo, sugerindo um novo mecanismo atravÃs do qual essa droga poderia exercer seus efeitos protetores.

The purpose of this project was to determine the time between arrival, assessment, and treatment for patients presenting with alcohol withdrawal syndrome (AWS) to the emergency department (ED) as well as to identify patient and environmental factors that may prolong initiation of the implementation of the clinical institute withdrawal alcohol (CIWA-Ar) protocol for assessment and treatment of AWS. There is clear evidence that rapid assessment and treatment of AWS improves cost, quality, risk, safety and patient outcomes. This project found that patients in the emergency department at Banner University Medical Center South campus (BUMCS) in 2016 on average waited 2 hours and 20 minutes for initial CIWA-Ar assessment and 50 minutes for medication to be administered. When taking into account the physiological process of AWS and the highly variable nature of ethanol metabolism this timeline is suboptimal and significant reduction of these times are recommended. The only factor that was significantly associated with increased wait times was elevated blood alcohol content (BAC). With higher BAC resulting in longer wait times. This is a concerning finding since patients experiencing symptoms of withdrawal in the presence of elevated BAC are at significantly higher risk for the most severe AWS including delirium tremens and seizure.