Anaesthetic impairment of immune function is mediated via GABA(A) receptors.

Background: GABA(A) receptors are members of the Cys-loop family of neurotransmitter receptors, proteins which are responsible for fast synaptic transmission, and are the site of action of wide range of drugs. Recent work has shown that Cys-loop receptors are present on immune cells, but their physiological roles and the effects of drugs that modify their function in the innate immune system are currently unclear. We are interested in how and why anaesthetics increase infections in intensive care patients; a serious problem as more than 50% of patients with severe sepsis will die.

Parcellating the neuroanatomical basis of impaired decision-making in traumatic brain injury.

Cognitive dysfunction is a devastating consequence of traumatic brain injury that affects the majority of those who survive with moderate-to-severe injury, and many patients with mild head injury. Disruption of key monoaminergic neurotransmitter systems, such as the dopaminergic system, may play a key role in the widespread cognitive dysfunction seen after traumatic axonal injury. Manifestations of injury to this system may include impaired decision-making and impulsivity.

Intracranial pressure: why we monitor it, how to monitor it, what to do with the number and what's the future?

Purpose Of Review: The review touches upon the current physiopathological concepts relating to the field of intracranial pressure (ICP) monitoring and offers an up-to-date overview of the ICP monitoring technologies and of the signal-analysis techniques relevant to clinical practice.

Recent Findings: Improved ICP probes, antibiotic-impregnated ventricular catheters and multimodality, computerized systems allow ICP monitoring and individualized optimization of brain physiology. Noninvasive technologies for ICP and cerebral perfusion pressure assessment are being tested in the clinical arena.

Cerebral extracellular chemistry and outcome following traumatic brain injury: a microdialysis study of 223 patients.

Secondary insults can adversely influence outcome following severe traumatic brain injury. Monitoring of cerebral extracellular chemistry with microdialysis has the potential for early detection of metabolic derangements associated with such events. The objective of this study was to determine the relationship between the fundamental biochemical markers and neurological outcome in a large cohort of patients with traumatic brain injury.

European society of intensive care medicine study of therapeutic hypothermia (32-35 °C) for intracranial pressure reduction after traumatic brain injury (the Eurotherm3235Trial).

Background: Traumatic brain injury is a major cause of death and severe disability worldwide with 1,000,000 hospital admissions per annum throughout the European Union.Therapeutic hypothermia to reduce intracranial hypertension may improve patient outcome but key issues are length of hypothermia treatment and speed of re-warming. A recent meta-analysis showed improved outcome when hypothermia was continued for between 48 hours and 5 days and patients were re-warmed slowly (1 °C/4 hours).

Changes in cerebral compartmental compliances during mild hypocapnia in patients with traumatic brain injury.

The benefit of induced hyperventilation for intracranial pressure (ICP) control after severe traumatic brain injury (TBI) is controversial. In this study, we investigated the impact of early and sustained hyperventilation on compliances of the cerebral arteries and of the cerebrospinal (CSF) compartment during mild hyperventilation in severe TBI patients. We included 27 severe TBI patients (mean 39.

Standardizing data collection in traumatic brain injury.

Collaboration among investigators, centers, countries, and disciplines is essential to advancing the care for traumatic brain injury (TBI). It is thus important that we "speak the same language." Great variability, however, exists in data collection and coding of variables in TBI studies, confounding comparisons between and analysis across different studies.

Changes in resting neural connectivity during propofol sedation.

Background: The default mode network consists of a set of functionally connected brain regions (posterior cingulate, medial prefrontal cortex and bilateral parietal cortex) maximally active in functional imaging studies under "no task" conditions. It has been argued that the posterior cingulate is important in consciousness/awareness, but previous investigations of resting interactions between the posterior cingulate cortex and other brain regions during sedation and anesthesia have produced inconsistent results.

Methodology/principal Findings: We examined the connectivity of the posterior cingulate at different levels of consciousness.

Traumatic brain injury.

There is an increasing incidence of military traumatic brain injury (TBI), and similar injuries are seen in civilians in war zones or terrorist incidents. Indeed, blast-induced mild TBI has been referred to as the signature injury of the conflicts in Iraq and Afghanistan. Assessment involves schemes that are common in civilian practice but, in common with civilian TBI, takes little account of information available from modern imaging (particularly diffusion tensor magnetic resonance imaging) and emerging biomarkers.

Common data elements for traumatic brain injury: recommendations from the interagency working group on demographics and clinical assessment.

Comparing results across studies in traumatic brain injury (TBI) has been difficult because of the variability in data coding, definitions, and collection procedures. The global aim of the Working Group on Demographics and Clinical Assessment was to develop recommendations on the coding of clinical and demographic variables for TBI studies applicable across the broad spectrum of TBI, and to classify these as core, supplemental, or emerging. The process was consensus driven, with input from experts over a broad range of disciplines.

Position statement: definition of traumatic brain injury.

A clear, concise definition of traumatic brain injury (TBI) is fundamental for reporting, comparison, and interpretation of studies on TBI. Changing epidemiologic patterns, an increasing recognition of significance of mild TBI, and a better understanding of the subtler neurocognitive neuroaffective deficits that may result from these injuries make this need even more critical. The Demographics and Clinical Assessment Working Group of the International and Interagency Initiative toward Common Data Elements for Research on Traumatic Brain Injury and Psychological Health has therefore formed an expert group that proposes the following definition: In this article, we discuss criteria for considering or establishing a diagnosis of TBI, with a particular focus on the problems how a diagnosis of TBI can be made when patients present late after injury and how mild TBI may be differentiated from non-TBI causes with similar symptoms.

Assessing quality of life after traumatic brain injury: examination of the short form 36 health survey.

Measuring health-related quality of life (HRQoL) has an important role in the comprehensive assessment of patient recovery following traumatic brain injury (TBI). We examined the validity of domain and summary scores derived from the Medical Outcomes Survey 36-Item Short Form Health Questionnaire (SF-36) as outcome measures for TBI in a prospective study of 514 patients with a range of functional impairment (Glasgow Outcome Scale-Extended [GOSE] scores 3-8). Item scaling criteria for the eight domain scores were tested and principal component analysis was used to examine if physical and mental component summary scores were valid.

Quantitative BOLD: the effect of diffusion.

Purpose: To make the quantitative blood oxygenation level-dependent (qBOLD) method more suitable for clinical application by accounting for proton diffusion and reducing acquisition times.

Materials And Methods: Monte Carlo methods are used to simulate the signal from diffusing protons in the presence of a blood vessel network. A diffusive qBOLD model was then constructed using a lookup table of the results.

Noninvasive monitoring of cerebrovascular reactivity with near infrared spectroscopy in head-injured patients.

Monitoring of cerebrovascular pressure reactivity (PRx) has diagnostic and prognostic value in head-injured patients, but requires invasive monitoring of intracranial pressure (ICP). Near infrared spectroscopy (NIRS) is a noninvasive method that is suitable for continuous detection of cerebral blood volume changes. We compared a NIRS-based index of cerebrovascular reactivity, called total hemoglobin reactivity (THx), against standard measurements of PRx in a prospective observational study.

The cytokine response to human traumatic brain injury: temporal profiles and evidence for cerebral parenchymal production.

The role of neuroinflammation is increasingly being recognised in a diverse range of cerebral pathologies, including traumatic brain injury (TBI). We used cerebral microdialysis and paired arterial and jugular bulb plasma sampling to characterise the production of 42 cytokines after severe TBI in 12 patients over 5 days. We compared two microdialysis perfusates in six patients: central nervous system perfusion fluid and 3.

A review of paroxysmal sympathetic hyperactivity after acquired brain injury.

Severe excessive autonomic overactivity occurs in a subgroup of people surviving acquired brain injury, the majority of whom show paroxysmal sympathetic and motor overactivity. Delayed recognition of paroxysmal sympathetic hyperactivity (PSH) after brain injury may increase morbidity and long-term disability. Despite its significant clinical impact, the scientific literature on this syndrome is confusing; there is no consensus on nomenclature, etiological information for diagnoses preceding the condition is poorly understood, and the evidence base underpinning our knowledge of the pathophysiology and management strategies is largely anecdotal.

Juguloarterial endothelin-1 gradients after severe traumatic brain injury.

Background: Endothelin-1 (ET-1) is a potent vasoconstrictor and is thought to be responsible for secondary ischemia and vasogenic edema after traumatic brain injury (TBI). Both CSF and plasma concentrations have been shown to be increased after TBI, but there is little evidence to confirm an intracranial site of production.

Methods: Using paired arterial and jugular venous bulb sampling, we measured arterial and jugular levels of ET-1 and its precursor, big endothelin (Big ET), and calculated juguloarterial (JA) gradients for the first 5 days post-TBI.

Rapid uptake of lipophilic triphenylphosphonium cations by mitochondria in vivo following intravenous injection: implications for mitochondria-specific therapies and probes.

Background: Mitochondrial dysfunction contributes to a range of pathologies, consequently there is a need to monitor mitochondrial function and to intervene pharmacologically to prevent mitochondrial damage. One approach to this is to deliver antioxidants, probes and pharmacophores to mitochondria by conjugation to the lipophilic triphenylphosphonium (TPP) cation that is taken up selectively by mitochondria driven by the membrane potential.

Conclusions: Oral administration of TPP-conjugated antioxidants protects against mitochondrial damage in vivo.

Brain microdialysis study of meropenem in two patients with acute brain injury.

Concentrations of unbound meropenem in the cerebral extracellular fluid (ECF) of two patients with acute brain injury were assessed by microdialysis. Brain ECF unbound-meropenem concentrations were lower than serum unbound-meropenem concentrations, with brain-to-serum area under the concentration-time curve ratios of 0.73 and 0.

Aetiological differences in neuroanatomy of the vegetative state: insights from diffusion tensor imaging and functional implications.

Background: An improved in vivo understanding of variations in neuropathology in the vegetative state (VS) may aid diagnosis, improve prognostication and help refine the selection of patients for particular treatment regimes. The authors have used diffusion tensor imaging (DTI) to characterise the extent and location of white matter loss in VS secondary to traumatic brain injury (TBI) and ischaemic-hypoxic injury.

Methods: Twelve patients with VS (seven TBI, five ischaemic/hypoxic injuries) underwent MRI including DTI at a minimum of 3 months postinjury.

Hierarchical log linear analysis of admission blood parameters and clinical outcome following traumatic brain injury.

Purpose: Numerous statistical methods have been utilised to generate predictive models that identify clinical and biochemical parameters of prognostic value following traumatic brain injury. While these methods provide an accurate statistical description between these variables and outcome, they are difficult to interpret intuitively. Hierarchical log linear analysis can be utilised to present the complex interactions between these variables and outcome visually.

Prediction of outcome in severe traumatic brain injury.

Purpose Of Review: Prognostic models for predicting outcome after severe traumatic brain injury (TBI) may be useful in several areas. However, established risk prediction models for general critical illness show significant limitations in neurotrauma. Development of specific risk prediction models for TBI has been difficult due to the variability of injury, which predicates a large sample for construction of robust models.

The human brain utilizes lactate via the tricarboxylic acid cycle: a 13C-labelled microdialysis and high-resolution nuclear magnetic resonance study.

Energy metabolism in the human brain is not fully understood. Classically, glucose is regarded as the major energy substrate. However, lactate (conventionally a product of anaerobic metabolism) has been proposed to act as an energy source, yet whether this occurs in man is not known.