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The application of clinical microdialysis to monitor changes in cerebral extracellular chemistry is now well established in several neurosurgical units worldwide. In neuro-intensive care the technique has been predominantly applied to patients with traumatic brain injury and subarachnoid haemorrhage. There is no doubt that microdialysis has increased and continues to increase our understanding of the pathophysiology of these conditions. Current studies are addressing the potential role of microdialysis as a clinical monitoring technique assisting in the management of patients on an intention to treat basis. This involves establishing the relationship between microdialysis and outcome, and the effect of therapeutic manoeuvres on the chemistry. This manuscript describes the place of microdialysis in traumatic brain injury in terms of the fundamental principles, methodology, pathophysiology and clinical application.

Cerebral ischemia is one of the most important causes of secondary insults following acute brain injury. While intracranial pressure monitoring in the intensive care unit constitutes the cornerstone of neurocritical care monitoring, it does not reflect the state of oxygenation of the injured brain. The holy grail of neuromonitoring is a modality that would reflect accurately real time the status of oxygenation in the tissue of interest, is robust, artefact free and that which provides information that can be used for therapeutic interventions and to improve outcome. Such a device could conceivably be used to augment the sensitivity of current multi-modality monitoring systems in the neurocritical management of brain injured patients. This article examines the availability of data in the literature to support clinical use of local tissue oxygen probes in intensive care.

The technique of near infrared spectroscopy (NIRS) is based on the principle of light attenuation by the chromophores oxyhaemoglobin (HbO), deoxyhaemoglobin (Hb) and cytochrome oxidase. Changes in the detected light levels can therefore represent changes in concentrations of these chromophores.

Clinical use of NIRS in the brain has been well established in neonates where transillumination is possible. While it has become a useful research tool for monitoring the adult brain, clinical application has been hampered by the fact that it must be applied in reflectance mode. This has resulted in a number of concerns, most significantly the issue of signal contamination by the extracranial tissue layers. Algorithms have been applied to try to overcome this problem, and techniques such as time resolved, phase resolved and spatially resolved spectroscopy have been developed.

There has been renewed interest in NIRS as an easy to use, noninvasive technique for measuring tissue oxygenation in the adult brain. Recent technical advances have led to the development of compact, portable instruments that detect changes in optical attenuation of several wavelengths of light.

Near infrared spectroscopy is an evolving technology that holds significant potential for technical advancement. In particular, NIRS shows future promise as a clinical tool for bedside cerebral blood flow measurements and as a cerebral imaging modality for mapping structure and function.

The heterogeneity of the initial insult and subsequent pathophysiology has made both the study of human head injury and design of randomised controlled trials exceptionally difficult. The combination of multimodality bedside monitoring and functional brain imaging positron emission tomography (PET) and magnetic resonance (MR), incorporated within a Neurosciences Critical Care Unit, provides the resource required to study critically ill patients after brain injury from initial ictus through recovery from coma and rehabilitation to final outcome. Methods to define cerebral ischemia in the context of altered cerebral oxidative metabolism have been developed, traditional therapies for intracranial hypertension re-evaluated and bedside monitors cross-validated. New modelling and analytical approaches have been developed.

Proteomics and peptidomics® are different and supplemental to genomics, since — in contrast to the basically constant genome — the proteome and peptidome are dynamic, constantly changing, and complex networks. Proteomics is traditionally linked to 2D-gel electrophoresis techniques. Concerning peptidomics, three different approaches are currently available, all using mass spectrometry as a key element. The use of proteomics or peptidomics in traumatic brain injury (TBI) research is demanding. From the technical point of view there are high-level requirements concerning the pre-analytical phase, specific machinery, sophisticated software and skilled manpower/intellectual input. There are currently no bedside techniques and most methods are suitable for experimental TBI research in specialized laboratories. In screening experiments of CSF following controlled cortical impact in rats we identified several peptides, which, although previously known, were so far not reported in the TBI context or in CSF. Peptidomics and proteomics, as highly complex screening technologies, thus seem to carry a large potential to lead TBI science. Newly “discovered” peptide targets have to be validated with different methodology to establish a real diagnostic or therapeutic value.

Much research interest has been shown in recent years for the development of molecular diagnostic strategies based on the analysis of DNA/RNA molecules that are present in the plasma/serum of human subjects. Reported applications include the diagnosis, prognostication or monitoring of malignancies and pregnancy-associated complications. While researchers have speculated that cell death is a potential mechanism that leads to the release of DNA/RNA into the circulation, studies have demonstrated that indeed increased amounts of plasma DNA and RNA could be detected in patients sustaining acute traumatic injuries. The degree of plasma DNA elevation correlated with the severity of injury. Similarly, plasma DNA concentrations have been shown to correlate with indices of prognostic significance in patients with acute stroke. It is expected that new diagnostic markers based on plasma RNA detection could be developed for the evaluation of acute pathologies.

The optimal therapy of sustained increase in intracranial pressure (ICP) is still controversial. The “Lund concept” is based on the physiological volume regulation of the intracranial compartments. In addition to its other functions the blood-brain barrier (BBB) is the most important regulator of brain volume. Water exchange across the intact BBB is counteracted by the low permeability to crystalloids (mainly Na and Cl) combined with the high osmotic pressure (5,700 mmHg) on both sides of the BBB. If the BBB is disrupted transcapillary water transport will be determined by the differences in hydrostatic and colloid osmotic pressure between the intra- and extracapillary compartments. Under pathological conditions pressure autoregulation of cerebral blood flow is often impaired and intracapillary hydrostatic pressure will depend on variations in systemic blood pressure.

The “Lund concept” can be summarized in four paragraphs: I. Reduction of stress response and cerebral energy metabolism; II. Reduction of capillary hydrostatic pressure; III. Maintenance of colloid osmotic pressure and control of fluid balance; IV. Reduction of cerebral blood volume. The efficacy of the treatment protocol has been evaluated in experimental and clinical studies regarding the physiological and biochemical (utilizing intracerebral microdialysis) effects. The clinical experiences have been favourable.