Lactate shuttling and lactate use as fuel after traumatic brain injury: metabolic considerations.
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ABSTRACT:
SUBMITTER: Dienel GA
PROVIDER: S-EPMC4269761 | biostudies-other | 2014 Nov
REPOSITORIES: biostudies-other
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Project description:Traumatic brain injury (TBI) has historically been viewed as a primarily male problem, since men are more likely to experience a TBI because of more frequent participation in activities that increase risk of head injuries. This male bias is also reflected in preclinical research where mostly male animals have been used in basic and translational science. However, with an aging population in which TBI incidence is increasingly sex-independent due to falls, and increasing female participation in high-risk activities, the attention to potential sex differences in TBI responses and outcomes will become more important. These considerations are especially relevant in designing preclinical animal models of TBI that are more predictive of human responses and outcomes. This review characterizes sex differences following TBI with a special emphasis on the contribution of the female sex hormones, progesterone and estrogen, to these differences. This information is potentially important in developing and customizing TBI treatments.
| S-EPMC6139061 | biostudies-literature
Project description:Complex alterations in cerebral energetic metabolism arise after traumatic brain injury (TBI). To date, methods allowing for metabolic evaluation are highly invasive, limiting our understanding of metabolic impairments associated with TBI pathogenesis. We investigated whether 13C MRSI of hyperpolarized (HP) [1-13C] pyruvate, a non-invasive metabolic imaging method, could detect metabolic changes in controlled cortical injury (CCI) mice (n = 57). Our results show that HP [1-13C] lactate-to-pyruvate ratios were increased in the injured cortex at acute (12/24 hours) and sub-acute (7 days) time points after injury, in line with decreased pyruvate dehydrogenase (PDH) activity, suggesting impairment of the oxidative phosphorylation pathway. We then used the colony-stimulating factor-1 receptor inhibitor PLX5622 to deplete brain resident microglia prior to and after CCI, in order to confirm that modulations of HP [1-13C] lactate-to-pyruvate ratios were linked to microglial activation. Despite CCI, the HP [1-13C] lactate-to-pyruvate ratio at the injury cortex of microglia-depleted animals at 7 days post-injury remained unchanged compared to contralateral hemisphere, and PDH activity was not affected. Altogether, our results demonstrate that HP [1-13C] pyruvate has great potential for in vivo non-invasive detection of cerebral metabolism post-TBI, providing a new tool to monitor the effect of therapies targeting microglia/macrophages activation after TBI.
| S-EPMC5727520 | biostudies-literature
Project description:ObjectiveTo summarize the current literature to identify what research has been conducted, examine the approaches used, and determine what is presently known about prescription and nonprescription opioid receipts and use among individuals with traumatic brain injury (TBI).Data sourcesThe search strategy included the following: opioid; opiate; analgesics, opioid; opiate alkaloids; or opioid-related disorders; AND brain injury; brain injuries; brain injuries, traumatic; head injury; head injuries; head injuries, closed; head injuries, penetrating; brain concussion; diffuse axonal injury; diffuse axonal injuries; brain trauma/s; head trauma/s; concussion; craniocerebral trauma/s; or TBI. Filters included English and Adults (19+ years). Study Selection: Inclusion: English language, adults with stable TBI, and prescription opioid receipt or use after TBI. Exclusion: Animal models, populations with other acquired brain injury, acute TBI management, and non-peer-reviewed articles, theses, or conference abstracts. Multiple reviewers screened abstracts and full-text articles for eligibility. In total, 771 abstracts were screened, 183 full texts were reviewed, and 21 met eligibility criteria. Data Extraction: Relevant content was independently extracted by multiple observers, including authors, design, sample identification and data source/s, TBI severity, TBI assessment, opioid assessment, study population (demographics, N), military affiliation, comparison groups, date of data collection, and summary of findings.ResultsStudies were published between 1987 and 2019; most data were collected prior to 2015. The majority utilized administrative and electronic medical record data from the Department of Veterans Affairs and retrospective cohort designs, and most focused on prescription opioids. There were no studies evaluating interventions to reduce use of opioids in TBI populations. Preliminary findings suggest that prescription opioid receipt is strongly related to psychological symptoms, including comorbid depression, anxiety, and posttraumatic stress disorder.ConclusionsDespite increased awareness of opioid receipt and use following TBI, there is limited investigation on the examination of this issue. Future studies should include more varied patient populations as well as evaluate interventions to reduce opioid use following TBI.
| S-EPMC8428300 | biostudies-literature
Project description:BackgroundLactate is used to evaluate the prognosis of adult patients with trauma. However, the prognostic significance of admission serum lactate in the setting of pediatric traumatic brain injury (TBI) is still unclear. We aim to investigate the impact of admission lactate on the outcome in children with moderate to severe TBI.MethodsThis retrospective study was conducted in a tertiary pediatric hospital between May 2012 and Jun 2018 included children with an admission Glasgow Coma Scale (GCS) of ≤13. Two hundred and thirteen patients were included in the analysis and 45 patients died in hospital.ResultsAdmission lactate and glucose were significantly higher in non-survivors than those in survivors (P < 0.05). Admission lactate was positively correlated with admission glucose and negatively correlated with GCS in all patients (n = 213), subgroup of isolated TBI (n = 112) and subgroup of GCS ≤ 8 (n = 133), respectively. AUCs of lactate could significantly predict the mortality and were higher than those of glucose in all patients, subgroup of isolated TBI and subgroup of GCS ≤ 8, respectively. Multivariate logistic regression showed that admission lactate (Adjusted OR = 1.189; 95% CI: 1.002-1.410; P = 0.047) was independently associated with mortality, while admission glucose (Adjusted OR = 1.077; 95% CI: 0.978-1.186; P = 0.133) wasn't an independent risk factor of death. Elevated admission lactate (> 2 mmol/L) was associated with death, reduced 14-day ventilation-free days, 14-day ICU-free days and 28-day hospital-free days.ConclusionsAdmission serum lactate can effectively predict the mortality of children with moderate to severe TBI. Elevated admission lactate is associated with death, reduced ventilator-free, ICU-free, and hospital-free days. Admission serum lactate could be used as a prognostic biomarker of mortality in children with moderate to severe TBI.
| S-EPMC6752785 | biostudies-literature
Project description:ObjectiveTo describe psychotropic medication administration patterns during inpatient rehabilitation for traumatic brain injury (TBI) and their relation to patient preinjury and injury characteristics.DesignProspective observational cohort.SettingMultiple acute inpatient rehabilitation units or hospitals.ParticipantsIndividuals with TBI (N=2130; complicated mild, moderate, or severe) admitted for inpatient rehabilitation.InterventionsNot applicable.Main outcome measuresNot applicable.ResultsMost frequently administered were narcotic analgesics (72% of sample), followed by antidepressants (67%), anticonvulsants (47%), anxiolytics (33%), hypnotics (30%), stimulants (28%), antipsychotics (25%), antiparkinson agents (25%), and miscellaneous psychotropics (18%). The psychotropic agents studied were administered to 95% of the sample, with 8.5% receiving only 1 and 31.8% receiving ≥6. Degree of psychotropic medication administration varied widely between sites. Univariate analyses indicated younger patients were more likely to receive anxiolytics, antidepressants, antiparkinson agents, stimulants, antipsychotics, and narcotic analgesics, whereas those older were more likely to receive anticonvulsants and miscellaneous psychotropics. Men were more likely to receive antipsychotics. All medication classes were less likely administered to Asians and more likely administered to those with more severe functional impairment. Use of anticonvulsants was associated with having seizures at some point during acute care or rehabilitation stays. Narcotic analgesics were more likely for those with history of drug abuse, history of anxiety and depression (premorbid or during acute care), and severe pain during rehabilitation. Psychotropic medication administration increased rather than decreased during the course of inpatient rehabilitation in each of the medication categories except for narcotics. This observation was also true for medication administration within admission functional levels (defined by cognitive FIM scores), except for those with higher admission FIM cognitive scores.ConclusionsMany psychotropic medications are used during inpatient rehabilitation. In general, lower admission FIM cognitive score groups were administered more of the medications under investigation compared with those with higher cognitive function at admission. Considerable site variation existed regarding medications administered. The current investigation provides baseline data for future studies of effectiveness.
| S-EPMC4516906 | biostudies-literature
Project description:ObjectivesTo characterize psychotropic medication use before and after traumatic brain injury (TBI) hospitalization among older adults. A secondary objective is to determine how receipt of indicated pharmacologic treatment for anxiety and post-traumatic stress disorder (PTSD) differs following TBI.DesignRetrospective cohort.SettingUnited States.ParticipantsMedicare beneficiaries aged ≥65 years hospitalized with TBI between 2006 and 2010 with continuous drug coverage for 12 months before and after TBI (N = 60,276).MeasurementsWe obtained monthly psychotropic medication use by drug class and specific drugs from Medicare Part D drug event files.ICD-9 codes were used to define anxiety (300.0x) and PTSD (309.81).ResultsAverage monthly prevalence of psychotropic medication use among all patients hospitalized for TBI was 44.8%; antidepressants constituted 73%. Prevalence of psychotropic medication use increased from 2006 to 2010. Following TBI, psychotropic medication use increased slightly (OR: 1.05; 95% CI: 1.03, 1.06.) Tricyclic antidepressant use decreased post-TBI (OR: 0.76; 95% CI: 0.73, 0.79) whereas use of the sedating antidepressants mirtazapine (OR: 1.31; 95% CI: 1.25, 1.37) and trazadone (OR: 1.11; 95% CI: 1.06, 1.17) increased. Antipsychotic (OR: 1.15; 95% CI: 1.12, 1.19) use also increased post-TBI. Beneficiaries newly diagnosed with anxiety (OR: 0.42; 95% CI: 0.36, 0.48) and/or PTSD (OR: 0.39; 95% CI: 0.18, 0.84) post-TBI were less likely to receive indicated pharmacologic treatment.ConclusionsOlder adults hospitalized with TBI have a high prevalence of psychotropic medication use yet are less likely to receive indicated pharmacological treatment for newly diagnosed anxiety and PTSD following TBI.
| S-EPMC5365362 | biostudies-literature
Project description:Traumatic brain injury (TBI) is one of the leading causes of death and disability around the world. The lack of validated biomarkers for TBI is a major impediment to developing effective therapies and improving clinical practice, as well as stimulating much work in this area. In this review, we focus on different settings of TBI management where blood or cerebrospinal fluid (CSF) biomarkers could be utilized for predicting clinically-relevant consequences and guiding management decisions. Requirements that the biomarker must fulfill differ based on the intended context of use (CoU). Specifically, we focus on fluid biomarkers in order to: (1) identify patients who may require acute neuroimaging (cranial computerized tomography (CT) or magnetic resonance imaging (MRI); (2) select patients at risk for secondary brain injury processes; (3) aid in counseling patients about their symptoms at discharge; (4) identify patients at risk for developing postconcussive syndrome (PCS), posttraumatic epilepsy (PTE) or chronic traumatic encephalopathy (CTE); (5) predict outcomes with respect to poor or good recovery; (6) inform counseling as to return to work (RTW) or to play. Despite significant advances already made from biomarker-based studies of TBI, there is an immediate need for further large-scale studies focused on identifying and innovating sensitive and reliable TBI biomarkers. These studies should be designed with the intended CoU in mind.
| S-EPMC5192512 | biostudies-literature
Project description:Decreases in energy metabolism following traumatic brain injury (TBI) are attributed to impairment of glycolytic flux and oxidative phosphorylation. Glucose utilization post-TBI is decreased while administration of alternative substrates has been shown to be neuroprotective. Changes in energy metabolism following TBI happens in two phases; a period of hyper-metabolism followed by prolonged hypo-metabolism. It is not understood how different cerebral metabolic states may impact substrate metabolism and ultimately mitochondrial function. Adult male or female Sprague Dawley rats were given sham surgery or controlled cortical impact (CCI) and were assigned one of two administration schemes. Glucose, lactate or beta-hydroxybutyrate (BHB) were infused i.v. either starting immediately after injury or beginning 6 h post-injury for 3 h to reflect the hyper- and hypo-metabolic stages. Animals were euthanized 24 h post-injury. The peri-contusional cortex was collected and assayed for mitochondrial respiration peroxide production, and citrate synthase activity. Tissue acetyl-CoA, ATP, glycogen and HMGB1 were also quantified. Sex differences were observed in injury pattern. Administration based on cerebral metabolic state identified that only early lactate and late BHB improved mitochondrial function and peroxide production and TCA cycle intermediates in males. In contrast, both early and late BHB had deleterious effects on all aspects of metabolic measurements in females. These data stress there is no one optimal alternative substrate, but rather the fuel type used should be guided by both cerebral metabolic state and sex.
| S-EPMC8168752 | biostudies-literature
Project description:Metabolic derangements following traumatic brain injury are poorly characterized. In this single-centre observational cohort study we combined 18F-FDG and multi-tracer oxygen-15 PET to comprehensively characterize the extent and spatial pattern of metabolic derangements. Twenty-six patients requiring sedation and ventilation with intracranial pressure monitoring following head injury within a Neurosciences Critical Care Unit, and 47 healthy volunteers were recruited. Eighteen volunteers were excluded for age over 60 years (n = 11), movement-related artefact (n = 3) or physiological instability during imaging (n = 4). We measured cerebral blood flow, blood volume, oxygen extraction fraction, and 18F-FDG transport into the brain (K1) and its phosphorylation (k3). We calculated oxygen metabolism, 18F-FDG influx rate constant (Ki), glucose metabolism and the oxygen/glucose metabolic ratio. Lesion core, penumbra and peri-penumbra, and normal-appearing brain, ischaemic brain volume and k3 hotspot regions were compared with plasma and microdialysis glucose in patients. Twenty-six head injury patients, median age 40 years (22 male, four female) underwent 34 combined 18F-FDG and oxygen-15 PET at early, intermediate, and late time points (within 24 h, Days 2-5, and Days 6-12 post-injury; n = 12, 8, and 14, respectively), and were compared with 20 volunteers, median age 43 years (15 male, five female) who underwent oxygen-15, and nine volunteers, median age 56 years (three male, six female) who underwent 18F-FDG PET. Higher plasma glucose was associated with higher microdialysate glucose. Blood flow and K1 were decreased in the vicinity of lesions, and closely related when blood flow was <25 ml/100 ml/min. Within normal-appearing brain, K1 was maintained despite lower blood flow than volunteers. Glucose utilization was globally reduced in comparison with volunteers (P < 0.001). k3 was variable; highest within lesions with some patients showing increases with blood flow <25 ml/100 ml/min, but falling steeply with blood flow lower than 12 ml/100 ml/min. k3 hotspots were found distant from lesions, with k3 increases associated with lower plasma glucose (Rho -0.33, P < 0.001) and microdialysis glucose (Rho -0.73, P = 0.02). k3 hotspots showed similar K1 and glucose metabolism to volunteers despite lower blood flow and oxygen metabolism (P < 0.001, both comparisons); oxygen extraction fraction increases consistent with ischaemia were uncommon. We show that glucose delivery was dependent on plasma glucose and cerebral blood flow. Overall glucose utilization was low, but regional increases were associated with reductions in glucose availability, blood flow and oxygen metabolism in the absence of ischaemia. Clinical management should optimize blood flow and glucose delivery and could explore the use of alternative energy substrates.
| S-EPMC8677561 | biostudies-literature
Project description:Time dependent-profiles in the gene expression level following lateral moderate fluid percussion injury in the rat brain We used microarray to elucidate relationship between the alteration of gene expression levels and the progression of brain damages following traumatic brain injury. To examine the levels of gene expression in the early phase of traumatic brain injury, we analyzed the gene expression at 3, 6, 12, and 48 h after trauma using the lateral moderate fluid percussion TBI model. The ratios of the gene expression level were compared between chips corresponding to the 3, 6 and 12 h fluid percussion groups and the sham group chips. On the other hand, the rations of gene expression level after 48 h FPI were compared with 48 h sham chip, because the gene expression levels of 48 h sham chip were distinct from sham group chips (3, 6 and 12 h) in the cluster and principal components analyses.
2010-12-07 | E-GEOD-24047 | biostudies-arrayexpress