Diss. (sammanfattning) Umeå : Umeå universitet, 2006. / Härtill 4 uppsatser.

Thesis (Ph. D.)--Michigan State University. Dept. of Neuroscience, 2008. / Title from PDF t.p. (viewed on Aug. 19, 2009) Includes bibliographical references (p. 294-324). Also issued in print.

Synaptic transmission is a mechanism that makes life possible for many organisms. Damaging this crucial process, such as with a buildup of Reactive Oxygen Species (ROS), is extremely detrimental for the entire organism. Previously, the Dawson-Scully lab has determined that exposure of the Drosophila melanogaster neuromuscular junction (NMJ) to ROS accumulation can result in synaptic failure at a faster rate than saline controls (Caplan et al., 2013). To combat such effects, novel three-dimensional Resveramorph compounds were created to act as a neuroprotective agent against the harmful effects of acute oxidative stress (Bollinger et al., 2019; Sial et al., 2019). With the initial Resveramorph compounds demonstrating neuroprotective effects, additional analysis of other Resveramorph compounds were of interest to better understand their role in neuroprotection. Further testing of these compounds allows for the investigation of how chemical structure affects a compound’s neuroprotective activity. / Includes bibliography. / Thesis (MS)--Florida Atlantic University, 2021. / FAU Electronic Theses and Dissertations Collection

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Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / A Pilocarpina à um agonista colinÃrgico caracterÃstico por induzir convulsÃes que evoluem para status epilÃpticus, similar à epilepsia do lobo temporal humana. Neste presente trabalho, nÃs avaliamos a possÃvel aÃÃo neuroprotetora da doxiciclina, uma tetraciclina de segunda geraÃÃo, nas convulsÃes induzidas pela pilocarpina em ratos Wistar machos, que receberam pilocarpina (300mg/kg i.p) presenÃa ou na ausÃncia de doxiciclina (25 à 100 mg/kg) administrada intraperitonealmente uma vez ao dia durante sete dias. ApÃs a injeÃÃo de pilocarpina, foram observados os sinais colinÃrgicos perifÃricos, as latÃncias de 1 convulsÃo e de morte. Foram determinadas as concentraÃÃes de aminoÃcidos no cÃrtex temporal atravÃs de cromatografia lÃquida de alta eficiÃncia HPLC, e a atividade do sistema antioxidante, catalase e as dosagens dos nÃveis de TBARS e nitrito. Os resultados mostraram que a doxiciclina nÃo alterou os sinais colinÃrgicos perifÃricos, contudo aumentou a latÃncia decorrida para a primeira convulsÃo (1.6 a 5 vezes), quando comparada ao grupo (P300). Resultados semelhantes foram demonstrados com a latÃncia de morte, que foi aumentada de 1.9 a 9.9 vezes. Observou - se que o prÃ-tratamento com doxiciclina 50 mg/kg foi capaz de reduzir em 25% os nÃveis de MDA, 64% os nÃveis de nitrito e 67.7% a atividade da catalase no cÃrtex temporal desses animais, demonstrando com clareza seu potencial antioxidante. Interessantemente, a doxiciclina diminuiu as concentraÃÃes de glutamato de 28 a 33%, e aumentou GABA em 112 e 91%, nas dose de 50 e 100mg/kg respectivamente nos animais administrados com P300, Na maior dose, a droga alterou os nÃveis de aspartato e taurina, diminuindo em 61% aspartato enquanto elevou os nÃveis de taurina em cerca de 34%. Surpreendentemente, somente a menor dose alterou os nÃveis de glicina, aumentendo a concentraÃÃo deste aminoÃcido em 132%. Em conclusÃo, mostramos que o inÃcio e a intensidade das convulsÃes induzidas pela pilocarpina foram significativamente reduzidos pela doxiciclina. Portanto, pelo menos em parte, este mecanismo de aÃÃo parece estar relacionado a uma diminuiÃÃo nos nÃveis de aminoÃcidos excitatÃrios e a um aumento nas concentraÃÃes de aminoÃcidos inibitÃrios no cÃrtex temporal desses animais. / Pilocarpine is known to induce convulsions leading to status epilepticus, similar to the temporal lobe epilepsy in humans. In the present work, we evaluated the possible protection affored by doxycyvline, a 2nd generation tetracycline, agaist pilocarpine- induced convulsions in male Wistar rats (P300mg/kg, i.p) in the absence and in the presence of doxicycline (25 to 100 mg/kg i.p.) daily for 7 days.After the pilocarpine injection, all groups were observed for cholinergic signs, latency to the first convulsion and latency to death. Besides, amino acid concentrations in temporal cÃrtices were determined by RP-HPLC, as well catalase activity and levels of TBARS and Nitrite. Results showed that doxycycline did not alter cholinergic signs but increased the latency time to the first convulsion (1.6 to 5 times increase), as compared to P300, and the highest effect was observed with the dose of 25 mg/kg. Similar results were demonstrated to death latency that increased from 1.9 to 9.9 times with doxyciclyne at the doses of 25, 50 and 100 mg/kg. In fact we showed that the pre-treatment with doxycycline decreased in 25% MDA levels, 64% nitrite levels and 67.7% catalase activity. Interestingly, doxycycline decreased glutamate concentrations in 28 and 33% and increased GABA in 112 and 91% at the doses of 50 and 100mg/kg respectively. At the higher dose the drug altered aspartate and taurine concentrations, decreased aspartate levels in 61%, while increasing taurine levels in 34%. Surprisingly, only the lower dose altered glycine levels, increasing its concentration by 132%. In conclusion, we showed that the onset and intensity of pilocarpine-induced seizures were significantly reduced by doxycycline. Furthermore, at least in part, its mechanism of action seems to be mediated by the decrease and increase of excitatory and inhibitory aminoacids, respectively. In addiction the doxycycline capacity to reduce the oxidative stress associated with the pilocarpine-induced may also play a role

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Thesis (Ph. D.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 181-212). Also available in print.

Acute glaucoma is an ocular emergency and sight -threatening disease which is caused by a sudden increase in intraocular ocular pressure (IOP) due to blockage of aqueous humor outflow. Acute glaucoma can result in permanent loss of visual acuity and visual field (VF). Prophylactic or therapeutic medicine is rare for acute glaucoma. In animal studies, a well-established model to investigate this acute IOP spike is by fluid infusion and adjustment of the fluid level to induce high IOP within a few seconds. However, there is no blockage of aqueous outflow and the increase in intraocular pressure is unrealistically rapid. To mimic the IOP profile in human acute glaucoma attack, we propose the use of an ophthalmic viscosurgical device (OVD), Healon 5 (AMO, Santa Ana, CA, USA) which is injected intracamerally to block aqueous outflow. The IOP is allowed to increase naturally inside the globe. We found that Healon 5 can induce an acute elevation in IOP with very similar characteristics to those observed in humans. For example, the IOP profile during the attack, changes in the anterior segment and retinal nerve fibre layer (RNFL) thinning are all consistent with findings in human acute angle closure glaucoma (AACG). We believed that our new model can more accurately reflect acute glaucoma than other animal models. Based on these findings we further tested the neuroprotective effect of Lycium barbarum polysaccharides (LBP) on retinal neurons against an acute rise in IOP (attack) with the new model. L. barbarum is an herb that has been used in Chinese medicine for thousands of years. The fruit of this plant is believed to be good for the health of the eyes. In our study we found that oral administration of LBP preceding an acute glaucoma attack can preserve the visual function of the animals despite the loss of neurons in the retinal ganglion cell layer (RGCL). L. barbarum intake seems to inhibit secondary cell death and progression of the disease. In conclusion, we had successfully established a new acute glaucoma attack animal model by intracameral injection of Healon 5. This model more closely resembles the condition observed in human acute glaucoma. We also found that LBP has a prophylactic neuroprotective effect against an acute glaucoma attack in animals. It can protect the visual function and possibly inhibit secondary cell death. Oral consumption of LBP as a health supplement may provide extra benefit to people who are at high risk of developing acute glaucoma, in addition to the protective effects of LBP against other diseases. / published_or_final_version / Anatomy / Master / Master of Philosophy

Glaucoma is a neurodegenerative disease and one of the major causes of blindness in the world. Secondary degeneration is involved in glaucoma. The retinal ganglion cells (RGCs) which are vulnerable to secondary degeneration in glaucoma are the promising target population for therapeutic intervention. Partial optic nerve transection (PONT) model has been established in the last decade. Primary and secondary degeneration can be separated in different regions of retinas in this model. Therefore, PONT is a good model for the study of mechanisms of secondary degeneration and the drug screening for secondary degeneration. Lycium barbarum (L. barbarum) has been shown to be neuroprotective for cortical neurons in vitro. It has also been shown that L. barbarum could delay RGCs death in a rat ocular hypertension model. In order to further investigate the effects of L. barbarum for RGCs, two models, complete optic nerve transaction (CONT) model and PONT model, were employed in my study. My results showed that the polysaccharide extract from L. barbarum (LBP) could partly prevent RGCs from death in the inferior retinas 4 weeks after PONT whereas it could not reduce the loss of RGCs after CONT. The1,1'-dioctadecyl-3, 3, 3’, 3’-tetramethylindocarbocyanine perchlorate(DiI) labeling of RGCs whose axons were transected showed that the majority of labeled cell bodies existed in the superior retinas. The result meant that more cell bodies in the superior retinas would die from primary degeneration than in the inferior retina after PONT. Therefore my results indicated that LBP protected RGCs which would die from secondary degeneration rather than primary degeneration. The results of Terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) staining showed that RGCs underwent apoptosis 1 week after PONT. Western-blot analysis demonstrated that oxidative stress was involved in the degeneration of RGCs after PONT. Furthermore, c-Jun N-terminal kinases (JNKs) pathway was activated which was indicated by an increase ofphospho-JNK2/3(p-JNK2/3)and phospho-c-jun(p-c-jun). Our results also revealed that orally feeding of LBP could increase the expression of manganese superoxide dismutase (MnSOD) and insulin growth factor-1 (IGF-1)and decrease the expression of p-JNK2/3 and p-c-jun. The results from optic nerve (ON) study showed that glial cells, including astrocytes and microglias/macrophages, were activated after PONT. Oxidative stress and inflammation were involved in the process. Secondary degeneration of ON was not obvious and LBP exerted no protective effects on the survival of axons in the ON. The multifocal electroretinography (mfERG) study showed that both the functions of inner retinas and outer retinas were damaged after PONT. The results indicated that other cell types or the synapses between different cell types were damaged in addition to RGCs. LBP could improve the function of the whole retinas, including both inner retinas and outer retinas after PONT. In conclusion, our results indicated that LBP protected RGCs from secondary degeneration via inhibiting oxidative stress and the activation of JNK pathway.LBP could also improve the function of both inner retinas and outer retinas after PONT. / published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy