Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue Rm FG-05, Toronto, ON M4N 3M5, Canada.
Curr Drug Targets. 2011 Feb;12(2):243-55. doi: 10.2174/138945011794182764.
Post-stroke cognitive impairment has a high prevalence in stroke patients and is associated with poor short and long term outcomes, including a negative impact on functional recovery. There is evidence that post-stroke impairment is the direct result of stroke induced neurological injury. Gray matter atrophy has been implicated in the development of post-stroke cognitive impairment and is the result of a series of neurochemical processes that are activated by ischemia. Lithium, traditionally used as a mood stabilizer, has been recognized in the last 10 years for its robust neuroprotective and neurotrophic effects against diverse insults, such as ischemia, both in vitro and in vivo. This has generated several preclinical and clinical studies of lithium treatment for managing neurodegenerative diseases and cerebral ischemia. Evidence suggests that lithium may protect against the cerebral atrophy and neuronal degeneration induced by the neurochemical processes and pathways known to regulate cell death and atrophy after an ischemic event. Lithium-mediated neurotroprotective and neurotrophic effects involve mechanisms highly relevant to the post-stroke population including the increased expression of brain-derived neurotrophic factor (BDNF) and Bcl-2, and inhibition of GSK-3β. Lithium-induced increases in human gray matter have been reported and occur within a time frame consistent with the known effects of lithium through increased expression of BDNF, Bcl-2 and GSK-3β inhibition. This article reviews the evidence to support the use of lithium to reduce neuronal damage post-stroke through 1) mechanisms of excitotoxicity and post-ischemic inflammation; and 2) neurotrophic signaling cascades. Lithium's relevant actions in preclinical and clinical studies will be reviewed and presented to support the neuroprotective and neurotrophic effects of lithium as well as other clinical considerations in using lithium in the post-ischemic stroke population.
中风后认知障碍在中风患者中发病率较高，与短期和长期预后不良有关，包括对功能恢复产生负面影响。有证据表明，中风后损伤是中风引起的神经损伤的直接结果。灰质萎缩与中风后认知障碍的发展有关，是一系列神经化学过程的结果，这些过程是由缺血激活的。在过去的 10 年中，传统上用作情绪稳定剂的锂因其对多种损伤（如缺血）的强大神经保护和神经营养作用而得到认可，无论是在体外还是体内。这引发了几项关于锂治疗管理神经退行性疾病和脑缺血的临床前和临床研究。有证据表明，锂可能通过调节缺血后已知的细胞死亡和萎缩的神经化学过程和途径来防止由这些过程和途径引起的脑萎缩和神经元变性。锂介导的神经保护和神经营养作用涉及与中风后人群高度相关的机制，包括脑源性神经营养因子 (BDNF) 和 Bcl-2 的表达增加，以及 GSK-3β 的抑制。据报道，锂可增加人类灰质，其发生时间与已知通过增加 BDNF、Bcl-2 和 GSK-3β 抑制表达的锂作用时间一致。本文综述了支持使用锂通过以下机制减少中风后神经元损伤的证据：1）兴奋性毒性和缺血后炎症的机制；和 2）神经营养信号级联。本文将回顾锂在临床前和临床研究中的相关作用，并提出支持锂的神经保护和神经营养作用的观点，以及在缺血性中风患者中使用锂的其他临床注意事项。
