Universiẗat, Diss.--Frankfurt/M., 2000.

Stuttgart, Univ., Diss., 2003.

Im Rahmen dieser Arbeit wurde das Motilitätsverhalten von Blut-Hirn Schranken-Endothelzellen unter ischämischen Bedingungen an Hand der cerebEND-Zelllinie untersucht. Da es bisher noch kein Modell für diese Fragestellung gab, wurde zunächst ein solches mit Hilfe des kommerziellen Motilitätsassay der Firma ibidi® etabliert. Danach konnte der Einfluss von ischämischen Bedingungen, von Astrozyten konditioniertem Medium (C6-Zelllinie) und letztendlich der therapeutische Ansatz durch Modulation des NMDA-Rezeptors untersucht werden. Dabei zeigte sich durch das C6-konditionierte Medium eine deutliche Zunahme der Motilität. Diese verstärkte Motilität konnte durch den NMDA-Rezeptor-Antagonisten MK801 verhindert werden. Trotz Analyse einiger an der Proliferation und Migration beteiligter Botenstoffe wie VEGF und MMPs konnte keine Regulation dieser durch MK801 nachgewiesen werden. / In this work, the motility behavior of blood-brain barrier endothelial cells under ischemic conditions was investigated using the cerebEND cell line. As there was no model for this question available until now, a model was first established using the commercial motility assay of the company ibidi®. Subsequently, the influence of ischemic conditions, astrocyte conditioned medium (C6-cell line) and finally the therapeutic approach by modulation of the NMDA receptor could be investigated. The C6-conditioned medium showed a significant increase in motility. This increased motility could be prevented by the NMDA receptor antagonist MK801. Despite analysis of some messenger substances involved in the proliferation and migration such as VEGF and MMPs, no regulation of these substances by MK801 could be detected.

Yes / Cognitive deficits in schizophrenia remain an unmet clinical need. Improved understanding of the neuro- and psychopathology of these deficits depends on the availability of carefully validated animal models which will assist the development of novel therapies. There is much evidence that at least some of the pathology and symptomatology (particularly cognitive and negative symptoms) of schizophrenia results from a dysfunction of the glutamatergic system which may be modelled in animals through the use of NMDA receptor antagonists. The current review examines the validity of this model in rodents. We review the ability of acute and sub-chronic treatment with three non-competitive NMDA antagonists; phencyclidine (PCP), ketamine and MK801 (dizocilpine) to produce cognitive deficits of relevance to schizophrenia in rodents and their subsequent reversal by first- and second-generation antipsychotic drugs. Effects of NMDA receptor antagonists on the performance of rodents in behavioural tests assessing the various domains of cognition and negative symptoms are examined: novel object recognition for visual memory, reversal learning and attentional set shifting for problem solving and reasoning, 5-Choice Serial Reaction Time for attention and speed of processing; in addition to effects on social behaviour and neuropathology. The evidence strongly supports the use of NMDA receptor antagonists to model cognitive deficit and negative symptoms of schizophrenia as well as certain pathological disturbances seen in the illness. This will facilitate the evaluation of much-needed novel pharmacological agents for improved therapy of cognitive deficits and negative symptoms in schizophrenia.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2015-12-10T08:13:00Z No. of bitstreams: 2 Dissertação - Jaqueline Andrade Ribeiro da Silva - 2015.pdf: 2794453 bytes, checksum: 2542dd17b29db760b73cc18f188703fd (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2015-12-10T08:14:50Z (GMT) No. of bitstreams: 2 Dissertação - Jaqueline Andrade Ribeiro da Silva - 2015.pdf: 2794453 bytes, checksum: 2542dd17b29db760b73cc18f188703fd (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2015-12-10T08:14:50Z (GMT). No. of bitstreams: 2 Dissertação - Jaqueline Andrade Ribeiro da Silva - 2015.pdf: 2794453 bytes, checksum: 2542dd17b29db760b73cc18f188703fd (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2015-04-29 / This study evaluated the analgesic effects of ketamine administered by three intravenous continuous infusionprotocols (IC) in bitches undergoing mastectomy. Twenty-five bitches were distributedrandomly in three groups: intraoperative continuous infusion group (CONTROL, n=8), receiving the IC only during the intraoperative period; 12-hour continuous infusion group (IC12, n=8), receiving the IC during the intraoperative period and for 12 hours after surgery; and 24-hour continuous infusion group (IC24, n=8), receiving the IC during the intraoperative period and for 24 hours after the surgery. Cardiorespiratory evaluations were performed during the perioperative period, and two researchers evaluated the postoperative analgesia by the interactive visual analog scale (VASi) and by the Short form of Glasgow composite pain scale (GCPS-SC), 10 minutes and 2, 4, 6, 8, 12, 18 and 24 hours after extubation. Owners evaluated their dogs using a questionnaire adapted from the "Helsinki Chronic Pain Index" on the 4th and 10th daysafter the surgical procedure. Pain scores and postoperative opioid requirements did not differ among groups. Rescue analgesia was administered to 7/8, 7/8 e 6/8 bitches in CONTROL, IC12 and IC24 groups, respectively. The main adverse effects observed were tachycardia, tachypnea, hypertension and excitement. According to the owners’ criteria, the animals of IC12 and IC24 groups had lower pain scores on the 4th and 10th days after the surgical procedure. We concluded that, although some mild adverse effects could occur, IC of ketamine is an effective and safe analgesic adjuvant in the early postoperative period. However, the main benefit of the prolonged Ketamine IC is probably related to the best quality of life andrecovery in the last postoperative period. / Neste estudo foi avaliada a eficácia analgésica da cetamina, administrada em três diferentes regimes de infusão intravenosa contínua (IC), em cadelas submetidas a mastectomia unilateral. Foram incluídas no estudo 24 cadelas, distribuídas em três grupos denominados: grupo infusão contínua transoperatória (CONTROLE, n=8), nas quais a IC da cetamina foi administrada somente durante o período transoperatório; grupo infusão contínua de 12 horas (IC12, n=8), as quais receberam a IC durante o período transoperatório e 12 horas após o término da cirurgia; e grupo infusão contínua de 24 horas (IC24, n=8), as quais receberam a IC durante o período transoperatório e 24 horas após o término da cirurgia. Os parâmetros cardiorrespiratórios foram avaliados durante o período perioperatório e aanalgesia pós-operatória foi avaliada de acordo com as escalas análoga visual interativa (VASi) eComposta de Glasgow(GCPS-SC). As avaliações foram realizadaspor dois pesquisadores 10 minutos, 2, 4, 6, 8, 12, 18 e 24 horas pós-extubação.Os proprietários avaliaram seus animais por meiodo―Helsinki Chronic Pain Index‖ no 4º e no 10º diasapós o procedimento cirúrgico. Os escores de dor e o requerimento de morfina no período pós-operatório não diferiram estaticamente entre os grupos. O resgate analgésico foi administrado em 7/8, 7/8 e 6/8 animais nos grupos CONTROLE, IC12 e IC24, respectivamente. Os principais efeitos adversos da IC de cetamina observados foram taquipnéia e hipertensão. Na avaliação dos proprietários os grupos IC12 e IC24 tiveram menores escores de dor no quarto e no décimo dia de pós-operatório. Concluiu-se que, apesar de poder ocasionar efeitos adversos discretos, a IC de cetamina é eficaz como adjuvante no fornecimento de analgesia no período pós-operatório imediato, maso principal benefício de seu uso provavelmente esteja relacionado com melhor recuperação e qualidade de vida no período pós-operatório tardio.