title: Translational neurochemical research in acute human brain injury: the current status and potential future for cerebral microdialysis.
abstract: Microdialysis (MD) was introduced as an intracerebral sampling method for clinical neurosurgery by Hillered et al. and Meyerson et al. in 1990. Since then MD has been embraced as a research tool to measure the neurochemistry of acute human brain injury and epilepsy. In general investigators have focused their attention to relative chemical changes during neurointensive care, operative procedures, and epileptic seizure activity. This initial excitement surrounding this technology has subsided over the years due to concerns about the amount of tissue sampled and the complicated issues related to quantification. The interpretation of mild to moderate MD fluctuations in general remains an issue relating to dynamic changes of the architecture and size of the interstitial space, blood-brain barrier (BBB) function, and analytical imprecision, calling for additional validation studies and new methods to control for in vivo recovery variations. Consequently, the use of this methodology to influence clinical decisions regarding the care of patients has been restricted to a few institutions. Clinical studies have provided ample evidence that intracerebral MD monitoring is useful for the detection of overt adverse neurochemical conditions involving hypoxia/ischemia and seizure activity in subarachnoid hemorrhage (SAH), traumatic brain injury (TBI), thromboembolic stroke, and epilepsy. There is some data strongly suggesting that MD changes precede the onset of secondary neurological deterioration following SAH, hemispheric stroke, and surges of increased ICP in fulminant hepatic failure. These promising investigations have relied on MD-markers for disturbed glucose metabolism (glucose, lactate, and pyruvate) and amino acids. Others have focused on trying to capture other important neurochemical events, such as excitotoxicity, cell membrane degradation, reactive oxygen species (ROS) and nitric oxide (NO) formation, cellular edema, and BBB dysfunction. However, these other applications need additional validation. Although these cerebral events and their corresponding changes in neurochemistry are important, other promising MD applications, as yet less explored, comprise local neurochemical provocations, drug penetration to the human brain, MD as a tool in clinical drug trials, and for studying the proteomics of acute human brain injury. Nevertheless, MD has provided new important insights into the neurochemistry of acute human brain injury. It remains one of very few methods for neurochemical measurements in the interstitial compartment of the human brain and will continue to be a valuable translational research tool for the future. Therefore, this technology has the potential of becoming an established part of multimodality neuro-ICU monitoring, contributing unique information about the acute brain injury process. However, in order to reach this stage, several issues related to quantification and bedside presentation of MD data, implantation strategies, and quality assurance need to be resolved. The future success of MD as a diagnostic tool in clinical neurosurgery depends heavily on the choice of biomarkers, their sensitivity, specificity, and predictive value for secondary neurochemical events, and the availability of practical bedside methods for chemical analysis of the individual markers. The purpose of this review was to summarize the results of clinical studies using cerebral MD in neurosurgical patients and to discuss the current status of MD as a potential method for use in clinical decision-making. The approach was to focus on adverse neurochemical conditions in the injured human brain and the MD biomarkers used to study those events. Methodological issues that appeared critical for the future success of MD as a routine intracerebral sampling method were addressed.
authors.affiliation: Division of Neurosurgery, Department of Surgery, The David Geffen UCLA School of Medicine, Los Angeles, California, USA. lars.hillered@neurokir.uu.se
authors.forename: Lars
authors.initials: L
authors.lastname: Hillered
authors.forename: Paul M
authors.initials: PM
authors.lastname: Vespa
authors.forename: David A
authors.initials: DA
authors.lastname: Hovda
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000601:surgery; D001930:Brain Injuries / Q000378:metabolism / Q000601:surgery; D006801:Humans; D017551:Microdialysis / Q000639:trends*; D019635:Neurosurgical Procedures / Q000639:trends
chemical_list: D015415:Biomarkers