Crespi Francesco, Cattini Stefano, Donini Maurizio, Bandera Andrea, Rovati Luigi
Biology Dept, GSK Verona, Verona, Italy.
Department of Engineering Enzo Ferrari, University of Modena and Reggio Emilia, Modena, Italy.
J Neurosci Methods. 2016 Jan 30;258:79-86. doi: 10.1016/j.jneumeth.2015.10.011. Epub 2015 Nov 6.
Near-infrared spectroscopy (NIRS) is a non-invasive technique that monitors changes in oxygenation of haemoglobin. The absorption spectra of near-infrared light differ for the oxygenation-deoxygenation states of haemoglobin (oxygenate (HbO2) and deoxygenate (Hb), respectively) so that these two states can be directly monitored.
COMPARISON WITH EXISTING METHOD(S): Different methodologies report different basal values of HbO2 and Hb absolute concentrations in brain. Here, we attempt to calculate basal HbO2 levels in rat CNS via evaluation of the influence of exogenous oxygen or exogenous carbon dioxide on the NIRS parameters measured in vivo.
Furthermore the possibility that changes of haemoglobin oxygenation in rat brain as measured by NIRS might be a useful index of brain penetration of chemical entities has been investigated. Different compounds from different chemical classes were selected on the basis of parallel ex vivo and in vivo pharmacokinetic (PK/PD) studies of brain penetration and overall pharmacokinetic profile.
It appeared that NIRS might contribute to assess brain penetration of chemical entities, i.e. significant changes in NIRS signals could be related to brain exposure, conversely the lack of significant changes in relevant NIRS parameters could be indicative of low brain exposure.
This work is proposing a further innovation on NIRS preclinical applications i.e. a "chemical" NIRS [chNIRS] approach for determining penetration of drugs in animal brain. Therefore, chNIRS could became a non invasive methodology for studies on neurobiological processes and psychiatric diseases in preclinical but also a translational strategy from preclinical to clinical investigations.
近红外光谱法（NIRS）是一种监测血红蛋白氧合变化的非侵入性技术。血红蛋白的氧合-脱氧状态（分别为氧合血红蛋白（HbO2）和脱氧血红蛋白（Hb））对近红外光的吸收光谱不同，因此可以直接监测这两种状态。
不同的方法报告了大脑中HbO2和Hb绝对浓度的不同基础值。在此，我们试图通过评估外源性氧气或外源性二氧化碳对体内测量的NIRS参数的影响，来计算大鼠中枢神经系统中的基础HbO2水平。
此外，还研究了通过NIRS测量的大鼠大脑中血红蛋白氧合变化可能是化学实体脑渗透的有用指标的可能性。根据脑渗透和整体药代动力学特征的平行体外和体内药代动力学（PK/PD）研究，从不同化学类别中选择了不同的化合物。
似乎NIRS可能有助于评估化学实体的脑渗透，即NIRS信号的显著变化可能与脑暴露有关，相反，相关NIRS参数缺乏显著变化可能表明脑暴露较低。
这项工作提出了NIRS临床前应用的进一步创新，即一种用于确定药物在动物脑中渗透的“化学”NIRS [chNIRS]方法。因此，chNIRS可以成为一种用于临床前神经生物学过程和精神疾病研究的非侵入性方法，也是从临床前到临床研究的转化策略。
