Novel Metabolomic Comparison of Arterial and Jugular Venous Blood in Severe Adult Traumatic Brain Injury Patients and the Impact of Pentobarbital Infusion.

Treatment of severe traumatic brain injury (TBI) in the intensive care unit focuses on controlling intracranial pressure, ensuring sufficient cerebral perfusion, and monitoring for secondary injuries. However, there are limited prognostic tools and no biomarkers or tests of the evolving neuropathology. Metabolomics has the potential to be a powerful tool to indirectly monitor evolving dysfunctional metabolism.

New astroglial injury-defined biomarkers for neurotrauma assessment.

Traumatic brain injury (TBI) is an expanding public health epidemic with pathophysiology that is difficult to diagnose and thus treat. TBI biomarkers should assess patients across severities and reveal pathophysiology, but currently, their kinetics and specificity are unclear. No single ideal TBI biomarker exists.

Acute glucose and lactate metabolism are associated with cognitive recovery following traumatic brain injury.

Traumatic brain injury (TBI) is associated with acute cerebral metabolic crisis (ACMC). ACMC-related atrophy appears to be prominent in frontal and temporal lobes following moderate-to-severe TBI. This atrophy is correlated with poorer cognitive outcomes in TBI.

Lactate supplementation in severe traumatic brain injured adults by primed constant infusion of sodium L-lactate.

Carbohydrate fuel augmentation following traumatic brain injury may be a viable treatment to improve recovery when cerebral oxidative metabolism of glucose is depressed. We performed a primed constant sodium L-lactate infusion in 11 moderate to severely brain injured adults. Blood was collected before and periodically during the infusion study.

Influence of Glycemic Control on Endogenous Circulating Ketone Concentrations in Adults Following Traumatic Brain Injury.

Background: The objective was to investigate the impact of targeting tight glycemic control (4.4-6.1 mM) on endogenous ketogenesis in severely head-injured adults.

Role of Metabolomics in Traumatic Brain Injury Research.

Metabolomics is an important member of the omics community in that it defines which small molecules may be responsible for disease states. This article reviews the essential principles of metabolomics from specimen preparation, chemical analysis, to advanced statistical methods. Metabolomics in traumatic brain injury has so far been underutilized.

A semi-automated workflow solution for multimodal neuroimaging: application to patients with traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of mortality and morbidity, placing a significant financial burden on the healthcare system worldwide. Non-invasive neuroimaging technologies have been playing a pivotal role in the study of TBI, providing important information for surgical planning and patient management. Advances in understanding the basic mechanisms and pathophysiology of the brain following TBI are hindered by a lack of reliable image analysis methods for accurate quantitative assessment of TBI-induced structural and pathophysiological changes seen on anatomical and functional images obtained from multiple imaging modalities.

Ketogenic diet decreases oxidative stress and improves mitochondrial respiratory complex activity.

Cerebral metabolism of ketones after traumatic brain injury (TBI) improves neuropathology and behavior in an age-dependent manner. Neuroprotection is attributed to improved cellular energetics, although other properties contribute to the beneficial effects. Oxidative stress is responsible for mitochondrial dysfunction after TBI.

Lactate: brain fuel in human traumatic brain injury: a comparison with normal healthy control subjects.

We evaluated the hypothesis that lactate shuttling helps support the nutritive needs of injured brains. To that end, we utilized dual isotope tracer [6,6-(2)H2]glucose, that is, D2-glucose, and [3-(13)C]lactate techniques involving arm vein tracer infusion along with simultaneous cerebral (arterial [art] and jugular bulb [JB]) blood sampling. Traumatic brain injury (TBI) patients with nonpenetrating brain injuries (n=12) were entered into the study following consent of patients' legal representatives.

Neurochemical cascade of concussion.

Primary Objective: The aim of this literature review was to systematically describe the sequential metabolic changes that occur following concussive injury, as well as identify and characterize the major concepts associated with the neurochemical cascade.

Research Design: Narrative literature review.

Conclusions: Concussive injury initiates a complex cascade of pathophysiological changes that include hyper-acute ionic flux, indiscriminant excitatory neurotransmitter release, acute hyperglycolysis and sub-acute metabolic depression.

Endogenous Nutritive Support after Traumatic Brain Injury: Peripheral Lactate Production for Glucose Supply via Gluconeogenesis.

We evaluated the hypothesis that nutritive needs of injured brains are supported by large and coordinated increases in lactate shuttling throughout the body. To that end, we used dual isotope tracer ([6,6-(2)H2]glucose, i.e.

Metabolomic analysis of cerebral spinal fluid from patients with severe brain injury.

Proton nuclear magnetic resonance (H-NMR) spectroscopic analysis of cerebral spinal fluid provides a quick, non-invasive modality for evaluating the metabolic activity of brain-injured patients. In a prospective study, we compared the CSF of 44 TBI patients and 13 non-injured control subjects. CSF was screened for ten parameters: β-glucose (Glu), lactate (Lac), propylene glycol (PG), glutamine (Gln), alanine (Ala), α-glucose (A-Glu), pyruvate (PYR), creatine (Cr), creatinine (Crt), and acetate (Ace).

Early metabolic crisis-related brain atrophy and cognition in traumatic brain injury.

Traumatic brain injury often results in acute metabolic crisis. We recently demonstrated that this is associated with chronic brain atrophy, which is most prominent in the frontal and temporal lobes. Interestingly, the neuropsychological profile of traumatic brain injury is often characterized as 'frontal-temporal' in nature, suggesting a possible link between acute metabolic crisis-related brain atrophy and neurocognitive impairment in this population.

The linear relationship between transcranial Doppler pulsatility indices and intracranial pressure is influenced by traumatic brain injury and vasospasm.

The pulsatility index (PI) and the intracranial -pressure (ICP) may or may not be correlated; the evidence to date differs widely. A study of multiple measures of PI and the corresponding ICP in patients with severe traumatic brain injury (TBI) showed that some of the relationships were moderately strong when calculated as conventional Pearson correlation coefficients. However, that method makes no adjustment of any kind for statistical outliers in the data.

Early nonischemic oxidative metabolic dysfunction leads to chronic brain atrophy in traumatic brain injury.

Chronic brain atrophy after traumatic brain injury (TBI) is a well-known phenomenon, the causes of which are unknown. Early nonischemic reduction in oxidative metabolism is regionally associated with chronic brain atrophy after TBI. A total of 32 patients with moderate-to-severe TBI prospectively underwent positron emission tomography (PET) and volumetric magnetic resonance imaging (MRI) within the first week and at 6 months after injury.

Intra-arterial calcium channel blocker infusion for treatment of severe vasospasm in traumatic brain injury: case report.

Objective: The authors describe a case of severe traumatic arterial vasospasm and its subsequent management using angiography and multiple infusions of calcium channel blockers.

Clinical Presentation: A 26-year-old man presented with subarachnoid hemorrhage and an initial Glasgow Coma Scale score of 4 after a motor vehicle accident. The patient underwent a bifrontal craniotomy and right frontal decompressive craniectomy for bilateral frontal epidural and subdural hematomas secondary to subarachnoid hemorrhage.

Persistent metabolic crisis as measured by elevated cerebral microdialysis lactate-pyruvate ratio predicts chronic frontal lobe brain atrophy after traumatic brain injury.

Objective: To determine whether persistent metabolic dysfunction in normal-appearing frontal lobe tissue is correlated with long-term tissue atrophy.

Design: Prospective monitoring with retrospective data analysis.

Setting: Single-center academic neurointensive care unit.

Nonconvulsive electrographic seizures after traumatic brain injury result in a delayed, prolonged increase in intracranial pressure and metabolic crisis.

Objective: To determine whether nonconvulsive electrographic post-traumatic seizures result in increases in intracranial pressure and microdialysis lactate/pyruvate ratio.

Design: Prospective monitoring with retrospective data analysis.

Setting: Single center academic neurologic intensive care unit.

Impaired percent alpha variability on continuous electroencephalography is associated with thalamic injury and predicts poor long-term outcome after human traumatic brain injury.

Continuous electroencephalography (cEEG) is potentially useful in determining prognosis in patients with traumatic brain injuries (TBI). The objective of this prospective, observational cohort study was to determine if the percent alpha variability (PAV) on cEEG was predictive of outcome following TBI. Injury characteristics were indexed to assess whether lesions in specific cerebral loci were correlated with PAV and patient recovery.

Estimation of hidden state variables of the Intracranial system using constrained nonlinear Kalman filters.

Impeded by the rigid skull, assessment of physiological variables of the intracranial system is difficult. A hidden state estimation approach is used in the present work to facilitate the estimation of unobserved variables from available clinical measurements including intracranial pressure (ICP) and cerebral blood flow velocity (CBFV). The estimation algorithm is based on a modified nonlinear intracranial mathematical model, whose parameters are first identified in an offline stage using a nonlinear optimization paradigm.

Increased pentose phosphate pathway flux after clinical traumatic brain injury: a [1,2-13C2]glucose labeling study in humans.

Patients with traumatic brain injury (TBI) routinely exhibit cerebral glucose uptake in excess of that expected by the low levels of oxygen consumption and lactate production. This brings into question the metabolic fate of glucose. Prior studies have shown increased flux through the pentose phosphate cycle (PPC) during cellular stress.

Nonlinear analysis of cerebral hemodynamic and intracranial pressure signals for characterization of autoregulation.

The objective of this study was to determine whether or not the underlying physiological systems that generates spontaneous arterial blood pressure (ABP), cerebral blood flow velocity (CBFV), and intracranial pressure signals could be adequately approximated as a linear stochastic process. Furthermore, a new measure (C) capable of capturing the degree of nonlinear dependency between two ABP and CBFV signals (including a time-varying situation) was proposed for quantifying the degree of cerebral blood flow autoregulation. A surrogate data test of fifteen ABP, CBFV, and intracranial pressure (ICP) segments was conducted for detecting whether there exists a statistically significant deviation from the null hypothesis of linear signals.

Posttraumatic vasospasm: the epidemiology, severity, and time course of an underestimated phenomenon: a prospective study performed in 299 patients.

Object: The purpose of this prospective study was to evaluate the cumulative incidence, duration, and time course of cerebral vasospasm after traumatic brain injury (TBI) in a cohort of 299 patients.

Methods: Transcranial Doppler (TCD) ultrasonography studies of blood flow velocity in the middle cerebral and basilar arteries (VMCA and VBA, respectively) were performed at regular intervals during the first 2 weeks posttrauma in association with 133Xe cerebral blood flow (CBF) measurements. According to current definitions of vasospasm, five different criteria were used to classify the patients: A (VMCA > 120 cm/second); B (VMCA > 120 cm/second and a Lindegaard ratio [LR] > 3); C (spasm index [SI] in the anterior circulation > 3.

Monitoring of cerebral blood flow and metabolism in traumatic brain injury.

The aim of the present study was to investigate the course of cerebral blood flow (CBF) and metabolism in traumatic brain injury (TBI) patients and to specifically characterize the changes in lactate and glucose indices in the acute post-traumatic period with regard to neurological condition and functional outcome. For this purpose, 55 consecutive TBI patients (mean age 37 +/- 17 years, mean GCS 6.8 +/- 3.