ENVIRONMENT OF LITHIUM IN RAT BRAIN IN VIVO

锂(Li)是治疗急性躁狂症的首选药物， 用于双相情感障碍的预防。关于以下问题几乎没有达成一致意见 LI是如何发挥其临床作用的，推测其起源 在神经元的细胞内空间。虽然相对容易做到 测量，血清锂浓度可能低于理想的 监测治疗，如治疗失败或神经毒性 标称的治疗性血清浓度很常见。因此，大脑 LI浓度可能是LI治疗的一个较好的指标。至 阐明其治疗作用和神经毒性的机制 因此，了解锂离子浓度对脑组织的影响是很重要的。 活体，包括整体和细胞内和细胞外 车厢。假设在达到稳定状态时， 体内锂在脑内的总体浓度与 大鼠的血药浓度。进一步的假设是，随着 长期给药(3周)，总的脑浓度 LI保持不变，但细胞内/细胞外的比率 增加。细胞内/细胞外比率缓慢增加 几次探寻将与李~S的时间进程相吻合 对人类的临床影响。局域化核磁共振光谱学是一种强大的 研究人体体内生化过程的工具和 动物。利用局域Li-7核磁共振波谱，大脑 体内的锂浓度将在一次和三次后进行测量 在治疗中以血药浓度给药数周的锂 以及人体内的毒性范围。Li-7自旋晶格(T1)与自旋 (T2)放松时间将在一周和三周后测量。 弛豫时间将提供有关离子迁移率和 结合、分隔和离子-组织相互作用。T2可以 无创性地估计细胞内/细胞外的比率 这可能会延伸到人类身上。这样的研究将支持 为人类开发可比的、非侵入性的方法。

Lithium (Li) is the treatment of choice for acute manic illness and for prophylaxis in bipolar disorder. There is little agreement as to how Li exerts its clinical effects, which are presumed to originate in the intracellular space of neurons. Although relatively easy to measure, the serum Li concentration may be less than ideal for monitoring treatment, as treatment failures or neurotoxicity at nominal therapeutic serum concentrations are common. Thus, the brain concentration of Li may be a better measure of Li therapy. To elucidate the mechanisms of therapeutic action and neurotoxic effects, it is important to know the Li concentration for brain in vivo, both overall and in the intracellular and extracellular compartments. It is hypothesized that, upon reaching steady state, the overall brain concentration of Li in vivo correlates well with serum concentration in rats. It is further hypothesized that, with longer term administration (3 weeks), the overall brain concentration of Li remains constant, but the intracellular/extracellular ratio increases. A slow increase of intracellular/extracellular ratio over several seeks would be consistent with the time course of Li~s clinical effects in humans. Localized NMR spectroscopy is a powerful tool for studying biochemical processes in vivo in humans and animals. Using localized Li-7 NMR spectroscopy, the brain concentration of Li in vivo will be measured after one and three weeks of Li administration at serum concentrations in the therapeutic and toxic ranges in humans. The Li-7 spin-lattice (T1) and spin-spin (T2) relaxation times will be measured after one and three weeks. The relaxation times will provide information on ionic mobility and binding, compartmentation, and ion-tissue interactions. The T2 may yield a noninvasive estimate of the intracellular/extracellular ratio that could be extended to humans. Such studies will support development of comparable, noninvasive approaches for humans.