ENVIRONMENT OF LITHIUM IN RAT BRAIN IN VIVO

锂（Li）是治疗急性躁狂症的首选， 来预防双相情感障碍 关于以下问题， 李是如何发挥其临床作用的，据推测， 在神经元的细胞内空间。 虽然相对容易 测量时，血清Li浓度可能低于理想水平， 监测治疗，因为治疗失败或神经毒性 标称治疗血清浓度是常见的。 因此，大脑 Li浓度可能是Li疗法的更好量度。 到 阐明治疗作用和神经毒性的机制 影响，重要的是要知道大脑中的Li浓度， 体内，无论是整体还是细胞内和细胞外 隔间 据推测，在达到稳态时， 体内Li的总脑浓度与 大鼠血清浓度。 进一步假设，随着 长期给药（3周），总体脑浓度 的Li保持恒定，但细胞内/细胞外比率 增大 细胞内/细胞外比率缓慢增加， 几次寻道与Li~s的时间过程是一致的 对人体的临床影响。 局部核磁共振光谱是一种强大的 用于研究人类体内生物化学过程的工具， 动物 使用局部Li-7 NMR光谱， 体内Li的浓度将在一次和三次之后测量。 在治疗组的血清浓度下， 和毒性范围。 Li-7自旋-晶格（T1）和自旋-自旋 (T2)在一周和三周后测量放松时间。 弛豫时间将提供关于离子迁移率的信息， 结合、区室化和离子-组织相互作用。 T2可以 产生细胞内/细胞外比率的非侵入性估计 可以扩展到人类。 这些研究将支持 为人类开发可比较的非侵入性方法。

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.