Department of Anesthesiology, PH 505, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, New York, NY 10032, USA.
J Neurooncol. 2011 Aug;104(1):11-9. doi: 10.1007/s11060-010-0466-4. Epub 2010 Dec 12.
The novel ability to quantify drug and tracer concentrations in vivo by optical means leads to the possibility of detecting and quantifying blood brain barrier (BBB) disruption in real-time by monitoring concentrations of chromophores such as Evan's Blue. In this study, experiments were conducted to assess the disruption of the BBB, by intraarterial injection of mannitol, in New Zealand white rabbits. Surgical preparation included: tracheotomy for mechanical ventilation, femoral and selective internal carotid artery (ICA) catheterizations, skull screws for monitoring electrocerebral activity, bilateral placement of laser Doppler probes and a small craniotomy for the placement of a fiber optic probe to determine tissue Evan's Blue dye concentrations. Evans Blue (6.5 mg/kg) was injected intravenously (IV) just before BBB disruption with intracarotid mannitol (25%, 8 ml/40 s). Brain tissue concentrations of the dye in mannitol-treated and control animals were monitored using the method of optical pharmacokinetics (OP) during the subsequent 60 min. Hemodynamic parameters, heart rate, blood pressure, and EKG remained stable throughout the experiments in both the control and the mannitol-treated group. Brain tissue concentrations of Evan's Blue and the brain:plasma Evan's Blue partition coefficient progressively increased during the period of observation. A wide variation in brain tissue Evan's Blue concentrations was observed in the mannitol group. The experiments demonstrate the feasibility of measuring tissue concentrations of Evan's Blue without invading the brain parenchyma, and in real-time. The data suggest that there are significant variations in the degree and duration of BBB disruption induced with intraarterial mannitol. The ability to optically monitor the BBB disruption in real-time could provide a feedback control for hypertonic disruption and/or facilitate dosage control for chemotherapeutic drugs that require such disruption.
新型光学方法可定量检测活体药物和示踪剂浓度，从而有可能通过监测伊文思蓝等发色团的浓度实时检测和定量血脑屏障 (BBB) 的破坏。在这项研究中，通过向颈内动脉内注射甘露醇来评估新西兰白兔 BBB 的破坏。手术准备包括：气管切开术进行机械通气、股动脉和选择性颈内动脉 (ICA) 插管、颅骨螺丝用于监测脑电活动、双侧放置激光多普勒探头和进行小颅骨切开术以放置光纤探头以确定组织伊文思蓝染料浓度。伊文思蓝 (6.5mg/kg) 在颈内动脉内注射甘露醇 (25%，8ml/40s) 之前静脉内 (IV) 注射。用光学药代动力学 (OP) 方法在随后的 60 分钟内监测甘露醇处理和对照动物的染料脑组织浓度。在对照和甘露醇处理组的整个实验过程中，血流动力学参数、心率、血压和心电图保持稳定。脑组织中伊文思蓝的浓度和脑：血浆伊文思蓝分配系数在观察期间逐渐增加。甘露醇组观察到脑组织伊文思蓝浓度的广泛变化。实验证明了无需侵犯脑实质即可实时测量组织中伊文思蓝浓度的可行性。数据表明，经动脉内甘露醇诱导的 BBB 破坏的程度和持续时间存在显著差异。实时光学监测 BBB 破坏的能力可为高渗破坏提供反馈控制，或为需要这种破坏的化学治疗药物提供剂量控制。
