Thelin Eric Peter, Carpenter Keri L H, Hutchinson Peter J, Helmy Adel
Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
AAPS J. 2017 Mar;19(2):367-376. doi: 10.1208/s12248-016-0027-7. Epub 2017 Jan 9.
Injuries to the central nervous system continue to be vast contributors to morbidity and mortality; specifically, traumatic brain injury (TBI) is the most common cause of death during the first four decades of life. Several modalities are used to monitor patients suffering from TBI in order to prevent detrimental secondary injuries. The microdialysis (MD) technique, introduced during the 1990s, presents the treating physician with a robust monitoring tool for brain chemistry in addition to conventional intracranial pressure monitoring. Nevertheless, some limitations remain, such as limited spatial resolution. Moreover, while there have been several attempts to develop new potential pharmacological therapies in TBI, there are currently no available drugs which have shown clinical efficacy that targets the underlying pathophysiology, despite various trials investigating a plethora of pharmaceuticals. Specifically in the brain, MD is able to demonstrate penetration of the drug through the blood-brain barrier into the brain extracellular space at potential site of action. In addition, the downstream effects of drug action can be monitored directly. In the future, clinical MD, together with other monitoring modalities, can identify specific pathological substrates which require tailored treatment strategies for patients suffering from TBI.
中枢神经系统损伤仍然是导致发病和死亡的主要原因;具体而言,创伤性脑损伤(TBI)是40岁前最常见的死亡原因。为预防有害的继发性损伤,人们采用了多种方法来监测TBI患者。20世纪90年代引入的微透析(MD)技术,为治疗医生提供了一种除传统颅内压监测外用于监测脑内化学物质的强大工具。然而,仍存在一些局限性,如空间分辨率有限。此外,尽管人们多次尝试开发针对TBI的新的潜在药物疗法,但目前尚无针对潜在病理生理学显示出临床疗效的可用药物,尽管进行了各种试验,研究了大量药物。特别是在大脑中,MD能够证明药物通过血脑屏障渗透到潜在作用部位的脑细胞外空间。此外,药物作用的下游效应可以直接监测。未来,临床MD与其他监测方式一起,可以识别特定的病理底物,从而为TBI患者制定量身定制的治疗策略。