Thesis (Ph. D.)--University of Texas at Austin, 1999. / Vita. Includes bibliographical references (leaves 183-192). Available also in a digital version from Dissertation Abstracts.

No description available.

Cerebral haemodynamic status defined as cerebral vasoreactivity to carbon dioxide and pressure autoregulatory response, have been shown to be affected after traumatic brain injury (TBI) and correlate with the neurological condition and clinical outcome. Therefore, it is important to have a reliable method to determine the cerebral haemodynamic status in brain-injured patients. Blood flow velocity (BFV) measurement by transcranial Doppler ultrasonography (TCD) has been shown to give accurate indication of changes in cerebral blood flow (CBF). Transient hyperaemic response (THR) test with TCD measurement to assess the BFV response of middle cerebral artery to a brief compression of the ipsilateral carotid artery, provides a simple method for repeated assessment of the cerebrovascular autoregulatory reserve in brain injured patients. However, the test has not been validated systematically against classical assessment tests using TCD and gold standard CBF measurement. / The aims of this thesis are (1) to validate the non-invasive TCD and its haemodynamic tests with a more involved gold standard CBF measurement using stable xenon-enhanced computerized tomography. (2) To correlate the cerebral haemodynamic abnormalities with the patterns of neurochemical disturbance detected by intracerebral microdialysis. (3) To investigate the possibility to reverse or minimized the cerebral haemodynamic abnormalities and metabolic derangement by treatment. (Abstract shortened by UMI.) / The goal of intensive care management for TBI is to provide them with a favourable physiological and metabolic environment for recovery of the injured-compromised cells. The development of clinical intracerebral microdialysis has enabled documentation of the metabolic derangement that provides more understanding of the mechanism of brain damage. Continuous measurement of both neurochemical and physiological parameters including CPP defined as mean arterial blood pressure (ABP) minus intracranial pressure, BFV and CBF, enables study of the relationship between metabolic events and physiologic changes. Clinical management of patients with TBI has emphasized on maintaining an optimal cerebral perfusion pressure (CPP). This critical CPP can then be defined by TCD, CBF as well as the metabolic measurements. / Ng Chi Ping. / "June 2005." / Adviser: Wai-sang Poon. / Source: Dissertation Abstracts International, Volume: 67-01, Section: B, page: 0122. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005 / Includes bibliographical references (p. 147-154). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Thesis (doctoral)--Lund University, 1995. / Added t.p. with thesis statement inserted.

OBJETIVO: Desenvolver e validar a técnica de CLAE-DE para o doseamento de dopamina (DA), ácido diidrofenilacético (DOPAC), ácido homovanílico (HVA) e 3-metoxitiramina (3-MT); validar a técnica de microdiálise (MD) cerebral em animais conscientes e avaliar o efeito do tratamento agudo com um extrato lipofílico das partes aéreas de Hypericum caprifoliatum (HCP) sobre os níveis cerebrais de DA e seus metabólitos. MATERIAIS E MÉTODOS: A validação analítica foi realizada conforme o preconizado pela ANVISA, com análise dos parâmetros linearidade, precisão, exatidão, especificidade e limite inferior de quantificação. A técnica de microdiálise foi realizada de forma clássica: guias de sonda foram implantadas nas regiões cerebrais de interesse por cirurgia estereotáxica; os dialisados foram obtidos, 48 horas após a cirurgia, através da perfusão da sonda com líquido cérebroespinhal artificial (1 μL/min) e coleta durante três horas, em intervalos de 20 min; as três primeiras coletas foram utilizadas para determinação da linha de base e só então foram administrados os tratamentos. Para a validação da MD a sonda foi implantada no estriado (A: -0,3; L: + 3,2; P: - 4,5) e o tratamento foi sulfato de anfetamina (2 mg/kg, s.c.). Para a avaliação do efeito de HCP, a sonda foi implantada no núcleo acumbens (A: +2,2; L: -1,5; P: -5,8) e o tratamento foi uma dose de 270 mg/kg do extrato (v.o.). RESULTADOS E DISCUSSÃO: Os parâmetros avaliados para validar o método analítico ficaram dentro dos limites especificados pela ANVISA. O sulfato de anfetamina produziu um aumento nos níveis extracelulares de DA em 160% e uma redução de DOPAC e de HVA em 80% e 50%, respectivamente. O extrato HCP não alterou o conteúdo intersticial de DA, DOPAC e HVA no núcleo acumbens. Os valores basais encontrados estão de acordo com dados relatados na literatura. Não foi possível quantificar 3-MT. CONCLUSÃO: A metodologia analítica e as condições experimentais de microdiálise utilizadas permitiram a mensuração de mudanças induzidas por anfetamina nos níveis extracelulares de DA e seus principais metabólitos demonstrando que os fundamentos da técnica estão estabelecidos em nossas condições. O regime de tratamento empregado com HCP não foi suficiente para alterar os níveis de DA e seus principais metabólitos no núcleo acumbens de ratos. / OBJECTIVE: The objectives of this work were to validate the HLPC-ED technique for measuring dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3- methoxytyramine (3-MT); to put into operation the brain microdialysis technique (MD) in freely moving rats; to evaluate, by using MD, the effect of a single treatment with lipophilic extract from aerial parts of Hypericum caprifoliatum (HCP) on DA, DOPAC, HVA and 3-MT brain levels. MATERIALS AND METHODS: In order to validate the analytical technique we followed the parameters established by ANVISA for bioanalytical samples. The parameters were: precision, accuracy, specificity and also the lower limit of quantitation. The microdialysis technique was carried out following classical procedures: male Wistar rats were submitted to stereotaxic surgery for the guide cannula implantation in the brain regions of interest; 48 hours later, the microdiaysis probe was inserted and perfused with cerebrospinal fluid (1 μL/min). After baseline samples collecting (1 h), the treatments were administrated and samples were collected every 20 min, during 2h. To accomplish MD technique validation the animals were treated with amphetamine sulfate (2 mg/kg, s.c.) and the extracellular levels of DA, DOPAC e HVA were measured in striatum (A: -0,3; L: + 3,2; P: - 4,5). The effect of HCP acute treatment (270 mg/kg, p.o.) was evaluated in nucleus accumbens (A: +2,2; L: -1,5; P: -5,8). RESULTS AND DISCUSSION: The analytical parameters values found were within the acceptable ranges for bio-analytical limits specified by ANVISA. As expected, amphetamine sulfate administration significantly increased DA (160%) extracellular levels and decreased DOPAC (80%) and HVA (50%) levels. The quantification of 3-MT was not possible. Acute HCP administration did not affected DA, DOPAC and HVA levels in the nucleus accumbens. CONCLUSION: The HPLC-ED methodology and microdialysis procedures employed allowed the detection of amphetamineinduced changes in extracellular levels of DA and its metabolites demonstrating that the technical starting point was acceptable. The acute administration of 270 mg/kg, p.o. of HCP to rats was not sufficient to modify the extracellular levels of DA, DOPAC and HVA in the nucleus accumbens.

OBJETIVO: Desenvolver e validar a técnica de CLAE-DE para o doseamento de dopamina (DA), ácido diidrofenilacético (DOPAC), ácido homovanílico (HVA) e 3-metoxitiramina (3-MT); validar a técnica de microdiálise (MD) cerebral em animais conscientes e avaliar o efeito do tratamento agudo com um extrato lipofílico das partes aéreas de Hypericum caprifoliatum (HCP) sobre os níveis cerebrais de DA e seus metabólitos. MATERIAIS E MÉTODOS: A validação analítica foi realizada conforme o preconizado pela ANVISA, com análise dos parâmetros linearidade, precisão, exatidão, especificidade e limite inferior de quantificação. A técnica de microdiálise foi realizada de forma clássica: guias de sonda foram implantadas nas regiões cerebrais de interesse por cirurgia estereotáxica; os dialisados foram obtidos, 48 horas após a cirurgia, através da perfusão da sonda com líquido cérebroespinhal artificial (1 μL/min) e coleta durante três horas, em intervalos de 20 min; as três primeiras coletas foram utilizadas para determinação da linha de base e só então foram administrados os tratamentos. Para a validação da MD a sonda foi implantada no estriado (A: -0,3; L: + 3,2; P: - 4,5) e o tratamento foi sulfato de anfetamina (2 mg/kg, s.c.). Para a avaliação do efeito de HCP, a sonda foi implantada no núcleo acumbens (A: +2,2; L: -1,5; P: -5,8) e o tratamento foi uma dose de 270 mg/kg do extrato (v.o.). RESULTADOS E DISCUSSÃO: Os parâmetros avaliados para validar o método analítico ficaram dentro dos limites especificados pela ANVISA. O sulfato de anfetamina produziu um aumento nos níveis extracelulares de DA em 160% e uma redução de DOPAC e de HVA em 80% e 50%, respectivamente. O extrato HCP não alterou o conteúdo intersticial de DA, DOPAC e HVA no núcleo acumbens. Os valores basais encontrados estão de acordo com dados relatados na literatura. Não foi possível quantificar 3-MT. CONCLUSÃO: A metodologia analítica e as condições experimentais de microdiálise utilizadas permitiram a mensuração de mudanças induzidas por anfetamina nos níveis extracelulares de DA e seus principais metabólitos demonstrando que os fundamentos da técnica estão estabelecidos em nossas condições. O regime de tratamento empregado com HCP não foi suficiente para alterar os níveis de DA e seus principais metabólitos no núcleo acumbens de ratos. / OBJECTIVE: The objectives of this work were to validate the HLPC-ED technique for measuring dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3- methoxytyramine (3-MT); to put into operation the brain microdialysis technique (MD) in freely moving rats; to evaluate, by using MD, the effect of a single treatment with lipophilic extract from aerial parts of Hypericum caprifoliatum (HCP) on DA, DOPAC, HVA and 3-MT brain levels. MATERIALS AND METHODS: In order to validate the analytical technique we followed the parameters established by ANVISA for bioanalytical samples. The parameters were: precision, accuracy, specificity and also the lower limit of quantitation. The microdialysis technique was carried out following classical procedures: male Wistar rats were submitted to stereotaxic surgery for the guide cannula implantation in the brain regions of interest; 48 hours later, the microdiaysis probe was inserted and perfused with cerebrospinal fluid (1 μL/min). After baseline samples collecting (1 h), the treatments were administrated and samples were collected every 20 min, during 2h. To accomplish MD technique validation the animals were treated with amphetamine sulfate (2 mg/kg, s.c.) and the extracellular levels of DA, DOPAC e HVA were measured in striatum (A: -0,3; L: + 3,2; P: - 4,5). The effect of HCP acute treatment (270 mg/kg, p.o.) was evaluated in nucleus accumbens (A: +2,2; L: -1,5; P: -5,8). RESULTS AND DISCUSSION: The analytical parameters values found were within the acceptable ranges for bio-analytical limits specified by ANVISA. As expected, amphetamine sulfate administration significantly increased DA (160%) extracellular levels and decreased DOPAC (80%) and HVA (50%) levels. The quantification of 3-MT was not possible. Acute HCP administration did not affected DA, DOPAC and HVA levels in the nucleus accumbens. CONCLUSION: The HPLC-ED methodology and microdialysis procedures employed allowed the detection of amphetamineinduced changes in extracellular levels of DA and its metabolites demonstrating that the technical starting point was acceptable. The acute administration of 270 mg/kg, p.o. of HCP to rats was not sufficient to modify the extracellular levels of DA, DOPAC and HVA in the nucleus accumbens.

OBJETIVO: Desenvolver e validar a técnica de CLAE-DE para o doseamento de dopamina (DA), ácido diidrofenilacético (DOPAC), ácido homovanílico (HVA) e 3-metoxitiramina (3-MT); validar a técnica de microdiálise (MD) cerebral em animais conscientes e avaliar o efeito do tratamento agudo com um extrato lipofílico das partes aéreas de Hypericum caprifoliatum (HCP) sobre os níveis cerebrais de DA e seus metabólitos. MATERIAIS E MÉTODOS: A validação analítica foi realizada conforme o preconizado pela ANVISA, com análise dos parâmetros linearidade, precisão, exatidão, especificidade e limite inferior de quantificação. A técnica de microdiálise foi realizada de forma clássica: guias de sonda foram implantadas nas regiões cerebrais de interesse por cirurgia estereotáxica; os dialisados foram obtidos, 48 horas após a cirurgia, através da perfusão da sonda com líquido cérebroespinhal artificial (1 μL/min) e coleta durante três horas, em intervalos de 20 min; as três primeiras coletas foram utilizadas para determinação da linha de base e só então foram administrados os tratamentos. Para a validação da MD a sonda foi implantada no estriado (A: -0,3; L: + 3,2; P: - 4,5) e o tratamento foi sulfato de anfetamina (2 mg/kg, s.c.). Para a avaliação do efeito de HCP, a sonda foi implantada no núcleo acumbens (A: +2,2; L: -1,5; P: -5,8) e o tratamento foi uma dose de 270 mg/kg do extrato (v.o.). RESULTADOS E DISCUSSÃO: Os parâmetros avaliados para validar o método analítico ficaram dentro dos limites especificados pela ANVISA. O sulfato de anfetamina produziu um aumento nos níveis extracelulares de DA em 160% e uma redução de DOPAC e de HVA em 80% e 50%, respectivamente. O extrato HCP não alterou o conteúdo intersticial de DA, DOPAC e HVA no núcleo acumbens. Os valores basais encontrados estão de acordo com dados relatados na literatura. Não foi possível quantificar 3-MT. CONCLUSÃO: A metodologia analítica e as condições experimentais de microdiálise utilizadas permitiram a mensuração de mudanças induzidas por anfetamina nos níveis extracelulares de DA e seus principais metabólitos demonstrando que os fundamentos da técnica estão estabelecidos em nossas condições. O regime de tratamento empregado com HCP não foi suficiente para alterar os níveis de DA e seus principais metabólitos no núcleo acumbens de ratos. / OBJECTIVE: The objectives of this work were to validate the HLPC-ED technique for measuring dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3- methoxytyramine (3-MT); to put into operation the brain microdialysis technique (MD) in freely moving rats; to evaluate, by using MD, the effect of a single treatment with lipophilic extract from aerial parts of Hypericum caprifoliatum (HCP) on DA, DOPAC, HVA and 3-MT brain levels. MATERIALS AND METHODS: In order to validate the analytical technique we followed the parameters established by ANVISA for bioanalytical samples. The parameters were: precision, accuracy, specificity and also the lower limit of quantitation. The microdialysis technique was carried out following classical procedures: male Wistar rats were submitted to stereotaxic surgery for the guide cannula implantation in the brain regions of interest; 48 hours later, the microdiaysis probe was inserted and perfused with cerebrospinal fluid (1 μL/min). After baseline samples collecting (1 h), the treatments were administrated and samples were collected every 20 min, during 2h. To accomplish MD technique validation the animals were treated with amphetamine sulfate (2 mg/kg, s.c.) and the extracellular levels of DA, DOPAC e HVA were measured in striatum (A: -0,3; L: + 3,2; P: - 4,5). The effect of HCP acute treatment (270 mg/kg, p.o.) was evaluated in nucleus accumbens (A: +2,2; L: -1,5; P: -5,8). RESULTS AND DISCUSSION: The analytical parameters values found were within the acceptable ranges for bio-analytical limits specified by ANVISA. As expected, amphetamine sulfate administration significantly increased DA (160%) extracellular levels and decreased DOPAC (80%) and HVA (50%) levels. The quantification of 3-MT was not possible. Acute HCP administration did not affected DA, DOPAC and HVA levels in the nucleus accumbens. CONCLUSION: The HPLC-ED methodology and microdialysis procedures employed allowed the detection of amphetamineinduced changes in extracellular levels of DA and its metabolites demonstrating that the technical starting point was acceptable. The acute administration of 270 mg/kg, p.o. of HCP to rats was not sufficient to modify the extracellular levels of DA, DOPAC and HVA in the nucleus accumbens.

In the neonatally 6-hydroxydopamine (6-OHDA)-lesioned rat hyperlocomotor activity, first described in the 1970s, was subsequently found to be increased by an additional lesion with 5,7-dihydroxytryptamine (5,7-DHT) (i.c.v.) in adulthood. The latter animal model (i.e., 134 μg 6-OHDA at 3 d postbirth plus 75 μg 5,7-DHT at 10 weeks; desipramine pretreatments) was used in this study, in an attempt to attribute hyperlocomotor attenuation by D,L-amphet-amine sulfate (AMPH) and m-chlorophenylpi-perazine di HCl (mCPP), to specific changes in extraneuronal (i.e., in vivo microdialysate) levels of dopamine (DA) and/or serotonin (5-HT). Despite the 98-99% reduction in striatal tissue content of DA, the baseline striatal microdialysate level of DA was reduced by 50% or less at 14 weeks, versus the intact control group. When challenged with AMPH (0.5 mg/kg), the microdialysate level of DA went either unchanged or was slightly reduced over the next 180 min (i.e., 20 min sampling), while in the vehicle group and 5,7-DHT (alone) lesioned group, the microdialysate level was maximally elevated by ∼225% and ∼450%, respectively - and over a span of nearly 2 h. Acute challenge with mCPP (1 mg/kg salt form) had little effect on microdialysate levels of DA, DOPAC and 5-HT. Moreover, there was no consistent change in the microdialysate levels of DA, DOPAC, and 5-HT between intact, 5-HT-lesioned rats, and DA-lesioned rats which might reasonably account for an attenuation of hyperlocomotor activity. These findings indicate that there are other important neurochemical changes produced by AMPH-and mCPP-attenuated hyperlocomotor activity, or perhaps a different brain region or multiple brain regional effects are involved in AMPH and mCPP behavioral actions.

To explore interactive deleterious effects of the teratogens ethanol and cadmium, pregnant rats were given cadmium (CdCl2, 50 ppm) and/or ethanol (10%), or tap water (controls) in the drinking water for the entire 21 days of pregnancy. At 3 months after birth, in vivo microdialysis was used to determine that there was a 4000% evoked release of DA by AMPH (AMPH, 4.0 mg/kg i.p.) in the striatum of rats exposed prenatally to both ethanol and cadmium, vs. a 2000% evoked release by AMPH in rats exposed prenatally to only ethanol or cadmium or tap water. Haloperidol (HAL)-evoked DA release was suppressed in groups exposed prenatally to ethanol, while HAL-evoked DOPAC and HVA release was greatest after co-exposure to prenatal cadmium and ethanol. These in vivo microdialysis results indicate that ontogenetic co-exposure to cadmium, and ethanol produces a long-lived suppressive effect on HAL-evoked DA release and a long-lived enhancing effect on AMPH-evoked DA release in rat striatum. These findings clearly demonstrate that there is marked alteration in dopaminergic regulation after ontogenetic cadmium and ethanol co-exposure, which in this regard resembles the reaction of the striatonigral pathway on AMPH-evoked DA release in rats with behavioral sensitization.

The intracellular second messenger nitric oxide (NO) is implicated in a variety of physiological functions, including release and uptake of dopamine (DA). In the described study, in vivo microdialysis and differential pulse voltammetric techniques were used to determine the involvement of NO in release of DA and its metabolites (dihydroxyphenylalanine, DOPAC; homovanillic acid, HVA) in neostriatum of freely moving rats. While the NO donor molsidomine (30.0 mg/kg; MOLS) and neuronal NO synthase- (nNOS-) inhbitor 7-nitroindazole (10.0 mg/kg; 7-NI) had no effect on the basal in vivo microdialysate level of DA, 7-NI specifically enhanced D,L-amphetamine- (1.0 mg/kg i.p.; AMPH) evoked release of DA. Basal or AMPH effects on DOPAC and HVA levels were not influenced by MOLS or 7-NI. Findings indicate that nitrergic systems have an important role in mediating effects of AMPH on dopaminergic systems.