Barten Donna M, Cadelina Gregory W, Weed Michael R
Genetically Defined Diseases, Bristol-Myers Squibb, Wallingford, CT, United States.
Genetically Defined Diseases, Bristol-Myers Squibb, Wallingford, CT, United States; RxGen, Inc, New Haven, CT, United States.
Handb Clin Neurol. 2017;146:47-64. doi: 10.1016/B978-0-12-804279-3.00004-6.
Cerebrospinal fluid (CSF) is a complex fluid filling the ventricular system and surrounding the brain and spinal cord. Although the bulk of CSF is created by the choroid plexus, a significant fraction derives from the interstitial fluid in the brain and spinal cord parenchyma. For this reason, CSF can often be used as a source of pharmacodynamic and prognostic biomarkers to reflect biochemical changes occurring within the brain. For instance, CSF biomarkers can be used to diagnose and track progression of disease as well as understand pharmacokinetic and pharmacodynamic relationships in clinical trials. To facilitate the use of these biomarkers in humans, studies in preclinical species are often valuable. This review summarizes methods for preclinical CSF collection for biomarkers from mice, rats, and nonhuman primates. In addition, dosing directly into CSF is increasingly being used to improve drug levels in the brain. Therefore, this review also summarizes the state of the art in CSF dosing in these preclinical species.
脑脊液（CSF）是一种充满脑室系统并环绕脑和脊髓的复杂液体。虽然大部分脑脊液由脉络丛产生，但相当一部分源自脑和脊髓实质中的间质液。因此，脑脊液通常可作为药效学和预后生物标志物的来源，以反映脑内发生的生化变化。例如，脑脊液生物标志物可用于诊断和跟踪疾病进展，以及了解临床试验中的药代动力学和药效学关系。为便于在人类中使用这些生物标志物，临床前物种的研究通常很有价值。本综述总结了从小鼠、大鼠和非人灵长类动物中采集用于生物标志物研究的临床前脑脊液的方法。此外，直接向脑脊液给药越来越多地用于提高脑内药物水平。因此，本综述还总结了这些临床前物种脑脊液给药的最新技术。
