NEUROPROTECTION--NICOTINE, CEMBRANOIDS, & NEUROTROPHINS

尼古丁在不同的实验模型和一些流行病学研究中显示出神经保护作用。众所周知，尼古丁使用引起的健康风险涉及血管损伤。但几乎没有神经元损伤尼古丁是一种成瘾性药物，会导致行为改变和大脑的生化变化。不同的尼古丁给药时间表产生不同的行为和生理效应。我们提出，这些行为和生理状态中的一些对应于不同程度或尼古丁介导的神经保护或以其他方式修改的兴奋性毒性的易感性的模式。尼古丁通常以复杂的混合物形式被人类摄入。我们描述了烟草和加勒比珊瑚中的西松烷类化合物抑制尼古丁的作用。最近，我们在香烟烟雾中发现了西松烷。因此，西松烷类化合物在尼古丁的健康影响中发挥作用是合理的。由于已知尼古丁会诱导神经营养因子的合成，这可以部分解释尼古丁诱导的神经保护作用。本文建议使用不同尼古丁给药方案处理的大鼠来测试行为、神经营养因子、几个脑区中的浓度和表达以及急性脑切片对NMDA毒性的敏感性。在本项目的最后一部分中，建议使用免疫组织学方法来研究神经营养素及其mRNA在脑切片中的分布。此外，建议测量不同尼古丁预处理对实验性局灶性缺血后损伤程度的影响。

Nicotine was shown to be neuroprotective in different experimental models and in some epidemiological studies. The well-known health risk caused by nicotine use involves vascular damage. but almost no neuronal damage. Nicotine is an addictive drug that causes behavioral modifications and biochemical changes in the brain. Different schedules of nicotine administration produce distinct behavioral and physiological effects. We propose that some of these behavioral and physiological states correspond to different degrees or modes of nicotine-mediated neuroprotection or otherwise modified susceptibility to excitotoxicity. Nicotine is usually taken in by humans in a complex mixture. We described that cembranoids from tobacco and Caribbean corals inhibit the effect of nicotine. Recently, we found cembranoids in cigarette smoke. Therefore it is plausible that cembranoids play a role in the health effects of nicotine. Since nicotine is known to induce the synthesis of neurotrophins, this could explain part of the nicotine-induced neuroprotection. It is proposed here to use rats treated with different nicotine administration regimens to test behavior, neurotrophin, concentration and expression in several brain areas and susceptibility to NMDA toxicity of acute brain slices. In the last part of this project it is proposed to use immunohistological methods to study the distribution of neurotrophins and their mRNAs in brain sections. In addition, it is proposed to measure the effect of different nicotine pre-treatments on the extent of damage after experimental focal ischemia.