| Summary: | 博士 === 國立臺灣大學 === 獸醫學研究所 === 103 === The present thesis report research on neurology and neurosurgery science through basic science and clinical practice. The thesis addresses the effects of clinical treatment for neurological disorders, in particular, neuropathic pain. Four studies were conducted which illustrated the effects of teriparatide on lung function and pain relief, the anti-inflammation effects of hydrocortisone treatment and anti-proliferative effects of a series of synthetic carbazole derivatives in glioblastoma cells. The first study was designed as the quatitative study which used both questionaire and physical examination with 37 participants to evaluate the the effects of teriparatide on lung function and pain relief. All of them completed 6 months treatment. We found that teriparatide treatment improves the lung function and results in diminished pain intensity in women with multiple osteoporotic vertebral compression fractures. The second study used a aminal model to examine the anti-inflammation effects of hydrocortisone treatment in 56 SD rats. Fifty-six SD rats were divided into seven groups, and were treated with insulin or hydrocortisone in sedentary or exercise training groups. The results showed that the serum glucose increased in hydrocortisone treatment accompanied by GLUT4 inactivation in both the sedentary and exercise training rats. In the exercise training groups, GLUT4 was redistributed on the plasma membrane on the co-treatment with insulin and hydrocortisone through Akt phosphorylation. Insulin treatment exerted a compensatory feedback effect on GLUT4 translocation on hydrocortisone cotreatment, which was the cause of GLUT4 inactivation. In the third study aims to design an innovative technique and apply it in dogs with spinal cord dysfunction. The results showed that in experienced hands, such a technique is as effective as traditional lumbar discectomy and decreases traumatizing the normal anatomy of the dorsal musculature and ligamentous structures. The newly developed sheath is inexpensive, disposable, and easy to use, and it can facilitate microscopic surgery. In final study, anti-glioblastoma profiles of a series of synthetic carbazole derivatives were evaluated in vitro. The most promising derivative in this series was BC3EE2,9B, which showed excellent anti-proliferative effects in GBM8401 and GBM8901 cells. BC3EE2,9B also triggered cell-cycle arrest, most prominently at the G1 stage, and suppressed glioblastoma cell invasion and migration. Furthermore, we found that BC3EE2,9B induced autophagy-mediated cell death and synergisticly sensitized GBM cells to temozolomide cytotoxicity. Our results provide molecular evidence for the mode of action governing the ability of BC3EE2,9B to sensitize drug-resistant glioblastoma cells to the chemotherapeutic agent temozolomide.
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