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Biomedical subjects

David A Hovda

Publications and source records attributed to David A Hovda.

At least 19 recordsLinked to original sources
PubMed2006

Metabolic maturation of the brain: a study of local cerebral protein synthesis in the developing cat.

We used quantitative L-[1-(14)C]leucine autoradiography to study the maturation of cerebral protein synthesis metabolism in kittens, starting at birth and through postnatal age (P) 180 days as well as in adult cats. We found that at birth most brain structures show protein synthesis (nmol/min/g; lCPS(leu)) rates already within the range of adult values (with some exceptions; e.g., the hippocampus and putamen). Likewise, most structures show a transient developmental peak during which the rates climb to levels higher than in adulthood. This peak often occurred at P60, but in some regions lasted from P30 to P90. Therefore, there is some regional heterogeneity in the maturation of brain protein synthesis. These results are compared with our previous findings on the maturation of cerebral glucose utilization and oxidative metabolism. We discuss the meaning of these maturational profiles in terms of time course of morphological development and of maturation of behavior in the cat. Correlations with findings in other mammalian species are also discussed.

Age Factors↗
PubMed2006

Lateral fluid percussion injury in the developing rat causes an acute, mild behavioral dysfunction in the absence of significant cell death.

Lateral fluid percussion injury (LFP), a model of mild-moderate concussion, leads to the temporary loss of the capacity for experience-dependent plasticity in developing rats. To determine if this injury-induced loss in capacity for plasticity is due to cell death, we conducted stereological measurements within the cerebral cortex and CA3 of the hippocampus 2 weeks following mild, moderate or severe LFP in the post-natal day 19 (P19) rat. Results indicated that there was no significant change in the absolute number of neurons, regardless of injury severity, in either the ipsilateral cortex (sham = 10.6 +/- 1.7, mild = 11.5 +/- 2.1, moderate = 10.0 +/- 1.0, severe = 10.9 +/- 1.3 million neurons) or CA3 region of the hippocampus (sham = 251 +/- 38, mild = 289 +/- 2, moderate = 245 +/- 48, severe = 255 +/- 62 thousand neurons). Even though there was no evidence of a significant degree of injury-induced cell death, animals exhibited cognitive deficits as revealed in a Morris water maze task (MWM). The MWM results indicated that regardless of injury severity, P19-injured rats exhibited a significant increase in escape latency compared to age-matched shams (injury by day; P < 0.001) and a significant increase in the number of trials needed to reach criterion (P < 0.05). Analysis of a probe trial one week post-MWM training, however, indicated that there was no deficit in storage or recall of the learned behavior as analyzed by platform hits (sham = 2.9 +/- 0.37, mild = 2.0 +/- 0.40, moderate = 1 +/- 0, severe = 2.8 +/- 0.62) or percent time spent in, or immediately surrounding, the platform area (sham = 13.5 +/- 1.71, mild = 10.8 +/- 2.32, moderate = 12.7 +/- 0, severe = 13.5 +/- 1.69). Taken together, these results indicate that while LFP in P19-injured animals does not lead to significant cell death, it does generate acute, mild deficits in MWM performance.

Age Factors↗
PubMed2006

Traumatic brain injury induced neuroprotection of retinal ganglion cells to optic nerve crush.

Optic nerve crush injury leads to death of retinal ganglion cells (RGCs), both as a direct result of the primary injury and via secondary degeneration induced by neurotoxins secreted by dying RGCs. Studies have shown that, if optic nerve crush is preceded by an unrelated injury to another part of the central nervous system, for example, the spinal cord, the ensuing T cell-mediated protective autoimmunity results in a significant increase in RGC survival. In this study, we used the controlled cortical impact paradigm to induce unilateral traumatic brain injury (TBI) in rats at different times before they were contralaterally subjected to a mild optic nerve crush. Survival of RGCs, assessed 2 weeks after crush injury, was significantly increased when the crush was inflicted 11 days after TBI, but not when the two injuries were concomitant. The beneficial effect was unaffected by injection of low-dose methylprednisolone MP (1 mg/kg), but was inhibited after a high-dose injection (30 mg/kg). Brain-derived neurotrophic factor (BDNF) mRNA, assayed at intervals after TBI, was increased in the retina ipsilateral to TBI but decreased in the contralateral retina. BDNF peaked 1 day after TBI, decreased on day 11, and rose again on day 21. It thus seems that brain injury sustained a certain time before optic nerve injury has a protective effect on RGC survival. This neuroprotective effect, which appears unrelated to retinal BDNF, is inhibited by high-dose MP, commonly used clinically to treat traumatic optic neuropathy.

Animals↗
PubMed2006

N-methyl-D-aspartate receptor subunit changes after traumatic injury to the developing brain.

Traumatic brain injury (TBI) is a major cause of disability in the pediatric population and can result in abnormal development. Experimental studies conducted in animals have revealed impaired plasticity following developmental TBI, even in the absence of significant anatomical damage. The N-methyl-D-aspartate receptor (NMDAR) is clearly involved in both normal development and in the pathophysiology of TBI. Following lateral fluid percussion injury in postnatal day (PND) 19 rats, we tested the hypothesis that TBI sustained at an early age would result in impaired NMDAR expression. Using immunoblotting and reverse transcriptase-polymerase chain reaction (RT-PCR), protein and RNA levels of NMDAR subunits were measured in the cerebral cortex and hippocampus on post-injury days (PID) 1, 2, 4, and 7 (though the PID7 analysis was only for protein) and compared with age-matched shams. Significant effects of hemisphere (analysis of variance [ANOVA], p<0.01), and interactions between hemisphere and injury (ANOVA, p<0.05) and hemisphere and PID (ANOVA, p<0.05) were found for synaptic protein levels of the NR2A subunit in hippocampus. Specifically, within the ipsilateral hippocampus, NR2A was reduced by 9.9%, 47.9%, 40.8%, and 6.3% on PID1, PID2, PID4, and PID7, respectively. Within the cortex, there was a significant effect of injury (ANOVA, p<0.05) without any hemispheric differences. These bilateral cortical reductions measured 30.5%, 3.2%, 5.7%, and 13.4% at the same timepoints after injury. Injury had no significant main effect on NR1 or NR2B protein levels. RT-PCR analysis showed no significant changes in NR1, NR2A, or NR2B gene expression; however, as a positive control, hsp70 was induced more than twofold in ipsilateral cortex and hippocampus on PID1. It is known that NR2A expression levels increase during normal development, and in response to environmental stimuli. Our data suggest that injury-induced reduction in the expression of NR2A is one likely mechanism for the impaired experience-dependent neuroplasticity seen following traumatic injury to the immature brain.

Animals↗
PubMed2005

Experience-dependent behavioral plasticity is disturbed following traumatic injury to the immature brain.

Traumatic brain injury (TBI) is most prevalent in children and young adults. The long-term effects of pediatric TBI include cognitive and behavioral impairments; however, over time, it is difficult to distinguish individual variability in intellect and behavior from sequelae of early injury. Postnatal day (PND) 19 rats underwent lateral fluid percussion (FP) injury, followed by rearing in either standard (STD) or enriched environment (EE) conditions. The hypothesis was that the traditional enhancement of cognitive functioning following EE rearing would be attenuated when this rearing is preceded by TBI at PND19. Thirty days after injury, Morris water maze (MWM) acquisition and subsequent probe trial retention were used to assess the behavioral effects of injury on experience-dependent plasticity induced by housing in EE at two different time windows. MWM acquisition demonstrated improvements following early EE rearing in both sham and injured animals; however, the degree of improvement was greater for uninjured animals. When EE rearing was delayed for 2 weeks after injury, the injury effect was absent and the effect of rearing even stronger. Memory testing in the early EE groups using a delayed probe trial showed an effect of injury and housing, with the sham EE animals benefiting the most. After the delayed EE, sham EE animals again showed more probe target hits, while FPEE animals did not, demonstrating an enduring memory deficit. These data confirm that early TBI has effects on experience-dependent plasticity resulting in long-term neurobehavioral deficits. In addition, the ability to benefit from environmental stimulation following TBI is dependent upon time after injury.

Adaptation, Psychological↗
PubMed2005

Routine and quantitative EEG in mild traumatic brain injury.

This article reviews the pathophysiology of mild traumatic brain injury, and the findings from EEG and quantitative EEG (QEEG) testing after such an injury. Research on the clinical presentation and pathophysiology of mild traumatic brain injury is reviewed with an emphasis on details that may pertain to EEG or QEEG and their interpretation. Research reports on EEG and QEEG in mild traumatic brain injury are reviewed in this setting, and conclusions are drawn about general diagnostic results that can be determined using these tests. QEEG strengths and weaknesses are reviewed in the context of factors used to determine the clinical usefulness of proposed diagnostic tests. Clinical signs, symptoms, and the pathophysiologic axonal injury and cytotoxicity tend to clear over weeks or months after a mild head injury. Loss of consciousness might be similar to a non-convulsive seizure and accompanied subsequently by postictal-like symptoms. EEG shows slowing of the posterior dominant rhythm and increased diffuse theta slowing, which may revert to normal within hours or may clear more slowly over many weeks. There are no clear EEG or QEEG features unique to mild traumatic brain injury. Late after head injury, the correspondence is poor between electrophysiologic findings and clinical symptoms. Complicating factors are reviewed for the proposed commercial uses of QEEG as a diagnostic test for brain injury after concussion or mild traumatic brain injury. The pathophysiology, clinical symptoms and electrophysiological features tend to clear over time after mild traumatic brain injury. There are no proven pathognomonic signatures useful for identifying head injury as the cause of signs and symptoms, especially late after the injury.

Animals↗
PubMed2005

Metabolic crisis without brain ischemia is common after traumatic brain injury: a combined microdialysis and positron emission tomography study.

Brain trauma is accompanied by regional alterations of brain metabolism, reduction in metabolic rates and possible energy crisis. We hypothesize that microdialysis markers of energy crisis are present during the critical period of intensive care despite the absence of brain ischemia. In all, 19 brain injury patients (mean GCS 6) underwent combined positron emission tomography (PET) for metabolism of glucose (CMRglu) and oxygen (CMRO(2)) and cerebral microdialysis (MD) at a mean time of 36 h after injury. Microdialysis values were compared with the regional mean PET values adjacent to the probe. Longitudinal MD data revealed a 25% incidence rate of metabolic crisis (elevated lactate/pyruvate ratio (LPR) > 40) but only a 2.4% incidence rate of ischemia. Positron emission tomography imaging revealed a 1% incidence of ischemia across all voxels as measured by oxygen extraction fraction (OEF) and cerebral venous oxygen content (CvO(2)). In the region of the MD probe, PET imaging revealed ischemia in a single patient despite increased LPR in other patients. Lactate/pyruvate ratio correlated negatively with CMRO(2) (P < 0.001), but not with OEF or CvO(2). Traumatic brain injury leads to a state of persistent metabolic crisis as reflected by abnormal cerebral microdialysis LPR that is not related to ischemia.

Acute Disease↗
PubMed2005

Upregulation of pentose phosphate pathway and preservation of tricarboxylic acid cycle flux after experimental brain injury.

The metabolic fate of [1,2 13C]-labeled glucose was determined in male control and unilateral controlled cortical impact (CCI) injured rats at 3.5 and 24 h after surgery. The concentration of 13C-labeled glucose, lactate, glutamate and glutamine were measured in the injured and contralateral cortex. CCI animals showed a 145% increase in 13C lactate in the injured cortex at 3.5 h, but not at 24 h after injury, indicating increased glycolysis in neurons and/or astrocytes ipsilateral to CCI. Total levels of 13C glutamate in cortical tissue extracts did not differ between groups. However, 13C glutamine increased by 40% in the left and 98% in the right cortex at 3.5 h after injury, most likely resulting from an increase in astrocytic metabolism of glutamate. Levels of 13C incorporation into the glutamine isotopomers had returned to control levels by 24 h after CCI. The singlet to doublet ratio of the lactate C3 resonances was calculated to estimate the flux of glucose through the pentose phosphate pathway (PPP). CCI resulted in bilateral increases (9-12%) in the oxidation of glucose via the PPP, with the largest increase occurring at 24 h. Since an increase in PPP activity is associated with NADPH generation, the data suggest that there was an increasing need for reducing equivalents after CCI. Furthermore, 13C was incorporated into glutamate and glutamine isotopomers associated with multiple turns of the tricarboxylic acid (TCA) cycle, indicating that oxidative phosphorylation of glucose was maintained in the injured cortex at 3.5 and 24 h after a moderate to severe CCI injury.

Animals↗
PubMed2005

Translational neurochemical research in acute human brain injury: the current status and potential future for cerebral microdialysis.

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.

Biomarkers↗
PubMed2005

Lateral fluid percussion brain injury: a 15-year review and evaluation.

This article comprehensively reviews the lateral fluid percussion (LFP) model of traumatic brain injury (TBI) in small animal species with particular emphasis on its validity, clinical relevance and reliability. The LFP model, initially described in 1989, has become the most extensively utilized animal model of TBI (to date, 232 PubMed citations), producing both focal and diffuse (mixed) brain injury. Despite subtle variations in injury parameters between laboratories, universal findings are evident across studies, including histological, physiological, metabolic, and behavioral changes that serve to increase the reliability of the model. Moreover, demonstrable histological damage and severity-dependent behavioral deficits, which partially recover over time, validate LFP as a clinically-relevant model of human TBI. The LFP model, also has been used extensively to evaluate potential therapeutic interventions, including resuscitation, pharmacologic therapies, transplantation, and other neuroprotective and neuroregenerative strategies. Although a number of positive studies have identified promising therapies for moderate TBI, the predictive validity of the model may be compromised when findings are translated to severely injured patients. Recently, the clinical relevance of LFP has been enhanced by combining the injury with secondary insults, as well as broadening studies to incorporate issues of gender and age to better approximate the range of human TBI within study design. We conclude that the LFP brain injury model is an appropriate tool to study the cellular and mechanistic aspects of human TBI that cannot be addressed in the clinical setting, as well as for the development and characterization of novel therapeutic interventions. Continued translation of pre-clinical findings to human TBI will enhance the predictive validity of the LFP model, and allow novel neuroprotective and neuroregenerative treatment strategies developed in the laboratory to reach the appropriate TBI patients.

Animals↗
PubMed2005

Restoration of cerebral vasoreactivity by an L-type calcium channel blocker following fluid percussion brain injury.

Traumatic brain injury (TBI) results in significant acute reductions in regional cerebral blood flow (rCBF). However, the mechanisms by which TBI impairs CBF and cerebral vascular reactivity have remained elusive. In the present study, the effect of verapamil, an L-type calcium (Ca(2+)) channel blocker, on post-traumatic vascular reactivity was evaluated following a lateral fluid percussion injury (FPI) in rats. rCBF was measured by [(14)C]-iodoantipyrine autoradiography 1 h after FPI. Following FPI, significant rCBF reductions were documented in all examined cortical areas. These reductions were the most prominent (72.0%) at the primary injury site. Intravenous infusion of verapamil (VE; 200 microg/kg/min), and norepinephrine (NE; 20 microg/mL/min) to maintain normal blood pressure, increased rCBF by 141.5% at the primary injury site when compared to untreated, FPinjured animals. Under stimulated conditions, both the ipsilateral and contralateral hemispheres failed to show any increases in rCBF at 1 h following FPI. In direct contrast, following VE+NE treatment all cortical areas measured showed near normal vascular reactivity to direct cortical stimulation (normal reactivity = 45% increase in rCBF vs. 47% increase in FPI+VE+NE cases). These findings suggest that the majority of post-traumatic hemodynamic depressions are closely related to mechanisms involving vasoconstriction. Furthermore, Ca(2+) may play a causative role in this vasoconstriction and the loss of vasoreactivity.

Animals↗
PubMed2004

Mitochondrial damage and dysfunction in traumatic brain injury.

The enduring cognitive deficits and histopathology associated with traumatic brain injury (TBI) may arise from damage to mitochondrial populations, which initiates the metabolic dysfunction observed in clinical and experimental TBI. The anecdotal evidence for in vivo structural damage to mitochondria corroborates metabolic and physiologic dysfunction, which depletes substrates and promotes free radical generation. Excessive calcium pathology differentially disrupts the heterogeneous mitochondrial population, such that calcium sensitivity increases after TBI. The ongoing pathology may escalate to include protein and DNA oxidation that impacts mitochondrial function and promotes cell death. Thus, in vivo TBI damages, if not eliminates, mitochondrial populations depending on injury severity, with the remaining population left to provide metabolic support for survival or repair in the wake of cellular pathology. With a considerable understanding of post-injury mitochondrial populations, therapeutic interventions targeted to the mitochondria may delay or prevent secondary cascades that lead to long-term cell death and neurobehavioral disability.

Journal Article↗
PubMed2004

Selective metabolic reduction in gray matter acutely following human traumatic brain injury.

The aim of this study was to determine whether the apparent loss of overall gray-white matter contrast (GM/WM) seen on FDG-PET imaging reflects the differential changes of glucose metabolic rate (CMRglc) in cortical gray mater (GM) and subcortical white mater (WM) following TBI. The clinical significance of the CMRglc GM-to-WM ratio was also evaluated. Nineteen normal volunteers and 14 TBI patients were studied. Each subject had a quantitative FDG-PET, a quantitative H215O-PET and a MR scan acutely following TBI. Stabilities of the global and regional FDG lumped constants (LC) were studied. Parametric images (pixel unit: mg/min/100g) of FDG uptake rate (CURFDG) and CMRglc were generated. The changes of CMR(glc) in whole brain, GM and WM were studied separately by using a MRI-segmentation-based technique. The GM-to-WM ratios of both CURFDG and CMRglc images were significantly (p < 0.001) decreased (>31%) in TBI patients. The global LC value reduced significantly (p < 0.01) in TBI patients. The CMRglc decreased significantly (p < 0.001) in GM but not in WM (p > 0.1). Kinetic analysis revealed significant (p < 0.001) decrease of GM hexokinase activity in TBI patients. The GM-to-WM ratios of CMRglc correlated (r = 0.64) with the initial Glasgow Coma Score (GCS) of TBI patients. The patients with higher CMRglc GM-to-WM ratios (>1.54) showed good recovery 12 months after TBI. There was a selective CMRglc reduction in cortical GM following TBI. The pathophysiological basis for the reduction in GM-to-WM CMRglc ratio seen on FDG-PET imaging following TBI remains to be determined.

Acute Disease↗
PubMed2004

Paradoxical effects of cortical impact injury on environmentally enriched rats.

Animals housed in an enriched environment develop thicker cortices, with increased numbers of dendrites, synapses, blood vessels, and glial cells. This study examines the responses of adult rats, developmentally reared in an enriched environment, to traumatic brain injury. Rats were placed in an enriched environment for 15 days, starting on postnatal day 21. Following enrichment, they were placed in standard vivarium conditions until adulthood. At 3 months of age, enriched and age-matched control rats received a mild unilateral controlled cortical impact and were allowed to recover for 41 days. During this time, they were examined for motor coordination deficits and for preferences in forelimb use. Results demonstrate that enriched animals had a larger contusion cavity and a greater initial deficit in forelimb use. However, this deficit quickly diminished in comparison to that seen in non-enriched injured rats. The deficit in motor coordination recovered more quickly in enriched rats, 1 week sooner than in controls. These data suggest that the response of enriched animals to brain injury results in more marked neurodegeneration and acute behavioral dysfunction, with a higher capacity for compensation and recovery.

Animals↗
PubMed2004

Differential gene expression in hippocampus following experimental brain trauma reveals distinct features of moderate and severe injuries.

Microarray technology was employed to determine the differential pattern of gene expression within the hippocampus as a result of traumatic brain injury (TBI). The validity of the microarray data was confirmed using real-time RT-PCR. Following either moderate or severe lateral fluid percussion injury, rats were studied 0.5, 4, and 24 h after injury. In general, animals exhibited mRNA up or down regulation of approximately 10% of the genes studied. However, it was clear that the pattern of gene expression was influenced by both the severity of injury and the time after injury at which animals were studied. For example, genes encoding molecules for cellular signaling, synaptic plasticity, metabolism, ion channels and transporters were up regulated following severe injury, but down regulated following moderate injury. Furthermore, moderate injury was associated with an increasing number of responsive genes as a function of time post-injury. However, animals sustaining a severe level of injury exhibited decreasing number of responsive genes during the same post-injury period. The different patterns of gene expression between injury severity and across time after the insult suggests that the pathophysiological cascade induced by TBI is accompanied by a molecular response which, like the other aspects of the cellular response for survival, may indicate a "molecular window" that may offer an opportunity for therapeutic interventions involving gene therapy. Our results also suggest that fundamentally different pathophysiological processes or cascades may be induced by different severities of injury.

Animals↗
PubMed2004

Subcortical white matter metabolic changes remote from focal hemorrhagic lesions suggest diffuse injury after human traumatic brain injury.

OBJECTIVE: We used positron emission tomographic studies to prospectively examine the relationship between glucose and oxidative metabolism in the subcortical white matter (WM) acutely after traumatic brain injury (TBI). The objective was to determine the nature, extent, and degree of metabolic abnormalities in subcortical brain regions remote from hemorrhagic lesions. METHODS: Sixteen normal volunteers and 10 TBI patients (Glasgow Coma Scale score, 4-10; age, 17-64 yr; 6 with focal and 4 with diffuse injury) were studied. Each subject underwent dynamic positron emission tomographic studies using [(15)O]CO, (15)O(2), [(15)O]H(2)O, and fluorodeoxyglucose plus a magnetic resonance imaging scan acutely after TBI. Parametric images of the metabolic rate of oxygen and metabolic rate of glucose were generated, and a molar oxygen-to-glucose utilization ratio was calculated. Data from gray matter and WM remote from hemorrhagic lesions, plus whole brain, were analyzed. RESULTS: There was a significant reduction in the subcortical WM oxygen-to-glucose utilization ratio after TBI compared with normal values (3.99 +/- 0.77 versus 5.37 +/- 1.00; P < 0.01), whereas the mean cortical gray matter and whole-brain values remained unchanged. WM metabolic changes, which were diffuse throughout the hemispheres, were characterized by a reduction in the metabolic rate of oxygen without a concomitant drop in the metabolic rate of glucose. CONCLUSION: The extent and degree of subcortical WM metabolic abnormalities after moderate and severe TBI suggest that diffuse WM injury is a general phenomenon after such injuries. This pervasive finding may indicate that the concept of focal traumatic injury, although valid from a computed tomographic imaging standpoint, may be misleading when considering metabolic derangements associated with TBI.

Adolescent↗
PubMed2004

Accuracy of a method using short inhalation of (15)O-O(2) for measuring cerebral oxygen extraction fraction with PET in healthy humans.

UNLABELLED: PET with short inhalation of (15)O-O(2) provides regional oxygen extraction fraction (OEF) in a shorter acquisition time and with less radiation exposure than does the steady-state method. The purpose of this study was to test the accuracy of the short-inhalation technique for estimating OEF in healthy human volunteers. METHODS: The final study population included 16 healthy volunteers, who underwent a series of dynamic PET scans consisting of short inhalation of (15)O-CO, short inhalation of (15)O-O(2), and a bolus infusion of (15)O-H(2)O to generate parametric images for cerebral blood volume (CBV), cerebral blood flow (CBF), OEF, and metabolic rate of oxygen (CMRO(2)). About 45 min before PET emission scanning, arterial and jugular blood was sampled through a catheter inserted in a radial artery and the right jugular bulb, respectively. PET-derived OEF (OEFpet) of the whole brain was compared with OEF calculated from the arteriovenous blood-sampling technique (OEFav). RESULTS: Whole-brain-averaged CBF (mean +/- SD) measured with PET was 0.40 +/- 0.06 (range, 0.30-0.55) mL/g/min, CBV was 0.05 +/- 0.01 (range, 0.04-0.09) mL/g, CMRO(2) was 2.85 +/- 0.39 (range, 2.35-3.84) mL/100 g/min, and OEFpet was 0.39 +/- 0.06 (range, 0.30-0.51). OEFpet showed a slightly higher value than did OEFav (0.36 +/- 0.05 [range, 0.29-0.46]), but the difference was not significant. The difference in the 2 measurements (OEFpet - OEFav) did not correlate with CBF (r = -0.16; P = not statistically significant [NS]), CBV (r = -0.20; P = NS), CMRO(2) (r = -0.16; P = NS), partial arterial oxygen pressure (r = 0.29; P = NS) or partial arterial carbon dioxide pressure (r = -0.17; P = NS). CONCLUSION: Compared with the arteriovenous blood-sampling technique, a technique using short inhalation of (15)O-O(2) did not significantly over- or underestimate global OEF in healthy human volunteers. The PET technique reasonably estimated the cerebral OEF in local brain tissues of healthy human volunteers.

Adult↗