Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 37
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
J Neurosci Res ; 96(4): 688-695, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28543565

RESUMO

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. We quantified global cerebral uptake of glucose and lactate and other systemic metabolites associated with energy metabolism. Our hypothesis was that cerebral lactate uptake, as measured by the arteriovenous difference of lactate (AVDlac), would increase in severely injured TBI patients in the neurocritical care unit. Infusion of sodium L-lactate changed net cerebral lactate release, where the arteriovenous difference of lactate is negative, to net cerebral lactate uptake. Results from a mixed effects model of AVDlac with the fixed effects of infusion time, arterial lactate concentration, arterial glucose concentration and arteriovenous difference of glucose shows that doubling arterial lactate concentration (from .92 to 1.84 mM) results in an increase in AVDlac from -.078 mM to .090 mM. We did not detect changes in systemic glucose during the course of the infusion study and observed significant changes in alanine (30% [20 39]), glutamine (34% [24 43]), acetate (87% [60 113]), valine (40% [28 51]), and leucine (24% [16 32]) from baseline levels. Further studies are required to establish the impact of lactate supplementation on cerebral and systemic flux of lactate, on gluconeogenesis, and on the impact on cerebral energetics following injury. © 2017 Wiley Periodicals, Inc.


Assuntos
Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/metabolismo , Ácido Láctico/metabolismo , Lactato de Sódio/uso terapêutico , Adulto , Idoso , Glicemia/metabolismo , Encéfalo/metabolismo , Metabolismo Energético/efeitos dos fármacos , Feminino , Humanos , Infusões Intravenosas , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Lactato de Sódio/administração & dosagem
2.
J Neurosci Res ; 96(4): 696-701, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28609544

RESUMO

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. The current study investigated ability of acute glucose and lactate metabolism to predict long-term recovery of frontal-temporal cognitive function in participants with moderate-to-severe TBI. Cerebral metabolic rate of glucose and lactate were measured by the Kety-Schmidt method on days 0-7 post-injury. Indices of frontal-temporal cognitive processing were calculated for six months post-injury; 12 months post-injury; and recovery (the difference between the six- and 12-month scores). Glucose and lactate metabolism were included in separate regression models, as they were highly intercorrelated. Also, glucose and lactate values were centered and averaged and included in a final regression model. Models for the prediction frontal-temporal cognition at six and 12 months post-injury were not significant. However, average glucose and lactate metabolism predicted recovery of frontal-temporal cognition, accounting for 23% and 22% of the variance, respectively. Also, maximum glucose metabolism, but not maximum lactate metabolism, was an inverse predictor in the recovery of frontal-temporal cognition, accounting for 23% of the variance. Finally, the average of glucose and lactate metabolism predicted frontal-temporal cognitive recovery, accounting for 22% of the variance. These data indicate that acute glucose and lactate metabolism both support cognitive recovery from TBI. Also, our data suggest that control of endogenous fuels and/or supplementation with exogenous fuels may have therapeutic potential for cognitive recovery from TBI.


Assuntos
Lesões Encefálicas Traumáticas/metabolismo , Cognição/fisiologia , Glucose/metabolismo , Ácido Láctico/metabolismo , Adulto , Lesões Encefálicas Traumáticas/complicações , Metabolismo Energético , Lobo Frontal , Escala de Coma de Glasgow , Humanos , Testes Neuropsicológicos , Lobo Temporal
3.
Neurocrit Care ; 26(2): 239-246, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27761730

RESUMO

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. METHODS: The data were prospectively collected during a randomized, within-patient crossover study comparing tight to loose glycemic control, defined as 6.7-8.3 mM. Blood was collected periodically during both tight and loose glycemic control epochs. Post hoc analysis of insulin dose and total nutritional provision was performed. RESULTS: Fifteen patients completed the crossover study. Total ketones were increased 81 µM ([38 135], p < 0.001) when blood glucose was targeted to tight (4.4-6.1 mM) compared with loose glycemic control (6.7-8.3 mM), corresponding to a 60 % increase. There was a significant decrease in total nutritional provisions (p = 0.006) and a significant increase in insulin dose (p = 0.008). CONCLUSIONS: Permissive underfeeding was tolerated when targeting tight glycemic control, but total nutritional support is an important factor when treating hyperglycemia.


Assuntos
Glicemia/análise , Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/terapia , Hiperglicemia/sangue , Hiperglicemia/terapia , Corpos Cetônicos/sangue , Avaliação de Resultados em Cuidados de Saúde , Adulto , Estudos Cross-Over , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Brain Inj ; 29(2): 139-53, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25587743

RESUMO

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. Additionally, these metabolic changes can subsequently lead to impaired neurotransmission, alternate fuel usage and modifications in synaptic plasticity and protein expression. The combination of these metabolic alterations has been proposed to cause the transient and prolonged neurological deficits that typically characterize concussion. Consequently, understanding the implications of the neurochemical cascade may lead to treatment and return-to-play guidelines that can minimize the chronic effects of concussive injury.


Assuntos
Traumatismos em Atletas/metabolismo , Concussão Encefálica/metabolismo , Cálcio/metabolismo , Neurotransmissores/metabolismo , Traumatismos em Atletas/fisiopatologia , Biomarcadores/metabolismo , Concussão Encefálica/fisiopatologia , Glicólise , Humanos , Recuperação de Função Fisiológica
5.
Acta Neurochir Suppl ; 118: 115-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23564115

RESUMO

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: ß-glucose (Glu), lactate (Lac), propylene glycol (PG), glutamine (Gln), alanine (Ala), α-glucose (A-Glu), pyruvate (PYR), creatine (Cr), creatinine (Crt), and acetate (Ace). Using mixed effects measures, we discovered statistically significant differences between control and trauma concentrations (mM). TBI patients had significantly higher concentrations of PG, while statistical trends existed for lactate, glutamine, and creatine. TBI patients had a significantly decreased concentration of total creatinine. There were no significant differences between TBI patients and non-injured controls regarding ß- or α-glucose, alanine, pyruvate or acetate. Correlational analysis between metabolites revealed that the strongest significant correlations in non-injured subjects were between ß- and α-glucose (r = 0.74), creatinine and pyruvate (r = 0.74), alanine and creatine (r = 0.62), and glutamine and α-glucose (r = 0.60). For TBI patients, the strongest significant correlations were between lactate and α-glucose (r = 0.54), lactate and alanine (r = 0.53), and α-glucose and alanine (r = 0.48). The GLM and multimodel inference indicated that the combined metabolites of PG, glutamine, α-glucose, and creatinine were the strongest predictors for CMRO2, ICP, and GOSe. By analyzing the CSF of patients with TBI, our goal was to create a metabolomic fingerprint for brain injury.


Assuntos
Aminoácidos/líquido cefalorraquidiano , Lesões Encefálicas/líquido cefalorraquidiano , Propilenoglicol/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Feminino , Glucose/líquido cefalorraquidiano , Humanos , Pressão Intracraniana , Espectroscopia de Ressonância Magnética , Masculino , Metabolômica , Pessoa de Meia-Idade , Prótons , Adulto Jovem
6.
Acta Neurochir Suppl ; 114: 11-5, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22327657

RESUMO

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. With the TBI patients demonstrating a large fraction of skewed measurements, a set of robust correlations were calculated that demonstrated that the apparent relationships between PI and ICP were entirely attributable to the statistical outliers. We conclude that the fundamental relationship of PI to ICP is weakly positive at best.


Assuntos
Lesões Encefálicas/diagnóstico por imagem , Lesões Encefálicas/fisiopatologia , Pressão Intracraniana/fisiologia , Vasoespasmo Intracraniano/diagnóstico por imagem , Vasoespasmo Intracraniano/fisiopatologia , Adolescente , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Lesões Encefálicas/cirurgia , Circulação Cerebrovascular , Feminino , Escala de Coma de Glasgow , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Neurocirurgia , Fatores Sexuais , Ultrassonografia Doppler Transcraniana , Vasoespasmo Intracraniano/cirurgia , Adulto Jovem
7.
J Neurotrauma ; 36(2): 212-221, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-29901425

RESUMO

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. We compared metabolite levels in simultaneously collected arterial and jugular venous samples in acute TBI patients undergoing intensive care as well as in healthy control volunteers. Our results show that, first, many circulating metabolites are decreased in TBI patients compared with healthy controls days after injury; both proline and hydroxyproline were depleted by ≥60% compared with healthy controls, as was gluconate. Second, both arterial and jugular venous plasma metabolomic analysis separates TBI patients from healthy controls and shows that distinct combinations of metabolites are driving the group separation in the two blood types. Third, TBI patients under heavy sedation with pentobarbital at the time of blood collection were discernibly different from patients not receiving pentobarbital. These results highlight the importance of accounting for medications in metabolomics analysis. Jugular venous plasma metabolomics shows potential as a minimally invasive tool to identify and study dysfunctional cerebral metabolism after TBI.


Assuntos
Biomarcadores/sangue , Lesões Encefálicas Traumáticas/metabolismo , Hipnóticos e Sedativos/uso terapêutico , Metabolômica/métodos , Pentobarbital/uso terapêutico , Adolescente , Adulto , Idoso , Lesões Encefálicas Traumáticas/tratamento farmacológico , Estudos de Coortes , Feminino , Humanos , Veias Jugulares , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
Crit Care Med ; 36(10): 2871-7, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18766106

RESUMO

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. PATIENTS: Fifteen patients with moderate to severe traumatic brain injury (Glasgow Coma Scale score 3-12). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hourly cerebral microdialysis was performed for the initial 96 hrs after trauma to determine extracellular levels of glucose, glutamate, glycerol, lactate, and pyruvate in normal appearing frontal lobes. Six months after injury, the anatomical outcome was assessed by measures of global and regional cerebral atrophy using volumetric brain magnetic resonance imaging. The lactate/pyruvate ratio was elevated >40 after traumatic brain injury in most patients, with a mean percent time of 32 +/- 29% of hours monitored. At 6 months after traumatic brain injury, there was a mean frontal lobe atrophy of 12 +/- 11% and global brain atrophy of 8.5 +/- 4.5%. The percentage of time of elevated lactate/pyruvate ratio correlated with the extent of frontal lobe brain atrophy (r = -.56, p < 0.01), but not global brain atrophy (r = -.31, p = 0.20). The predictive effect of lactate/pyruvate ratio was independent of patient age, Glasgow Coma Scale score, and volume of frontal lobe contusion. CONCLUSION: Persistent metabolic crisis, as reflected by an elevated lactate/pyruvate ratio, in normal appearing posttraumatic frontal lobe, is predictive of the degree of tissue atrophy at 6 months.


Assuntos
Encefalopatias/patologia , Lesões Encefálicas/diagnóstico , Lobo Frontal/patologia , Ácido Láctico/análise , Ácido Pirúvico/análise , Adolescente , Adulto , Atrofia/etiologia , Atrofia/patologia , Biomarcadores/análise , Encefalopatias/etiologia , Lesões Encefálicas/complicações , Lesões Encefálicas/terapia , Doença Crônica , Estudos de Coortes , Estado Terminal/mortalidade , Estado Terminal/terapia , Feminino , Seguimentos , Escala de Coma de Glasgow , Humanos , Escala de Gravidade do Ferimento , Unidades de Terapia Intensiva , Masculino , Microdiálise/métodos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X
9.
J Cereb Blood Flow Metab ; 27(9): 1593-602, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17293841

RESUMO

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. This study assessed the PPC after TBI in humans. [1,2-(13)C(2)]glucose was infused for 60 mins in six consented, severe-TBI patients (GCS<9) and six control subjects. Arterial and jugular bulb blood sampled during infusion was analyzed for (13)C-labeled isotopomers of lactate by gas chromatography/mass spectroscopy. The product of lactate concentration and fractional abundance of isotopomers was used to determine blood concentration of each isotopomer. The difference of jugular and arterial concentrations determined cerebral contribution. The formula PPC=(m1/m2)/(3+(m1/m2)) was used to calculate PPC flux relative to glycolysis. There was enrichment of [1,2-(13)C(2)]glucose in arterial-venous blood (enrichment averaged 16.6% in TBI subjects and 28.2% in controls) and incorporation of (13)C-label into lactate, showing metabolism of labeled substrate. The PPC was increased in TBI patients relative to controls (19.6 versus 6.9%, respectively; P=0.002) and was excellent for distinguishing the groups (AUC=0.944, P<0.0001). No correlations were found between PPC and other clinical parameters, although PPC was highest in patients studied within 48 h of injury (averaging 33% versus 13% in others; P=0.0006). This elevation in the PPC in the acute period after severe TBI likely represents a shunting of substrate into alternative biochemical pathways that may be critical for preventing secondary injury and initiating recovery.


Assuntos
Lesões Encefálicas/metabolismo , Encéfalo/metabolismo , Glucose/metabolismo , Via de Pentose Fosfato/fisiologia , Adolescente , Adulto , Idoso , Glicemia/análise , Radioisótopos de Carbono , Circulação Cerebrovascular/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
J Neurotrauma ; 24(4): 579-90, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17439342

RESUMO

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. Fifty-three TBI patients were studied using cEEG recording and serial neuroimaging. Clinical recovery was assessed at regular intervals in hospital and following discharge. The principal outcome measures included the mean 3-day PAV score, the 7-day PAV pattern, delineation of the anatomical sites of brain injury, and the 6-month clinical outcome, as measured by the Glasgow Outcome Scale (GOS). Significant univariate (p = 0.030) and multivariate (p = 0.008) relations were identified between PAV and GOS scores. PAV offered good discrimination between favorable and unfavorable 6-month outcomes (AUC 0.76) and, with a cutpoint of 0.20, had a sensitivity of 87% and negative predictive value of 82%. Multivariate modeling revealed that injuries of the thalamus (p = 0.009) and basal ganglia (p = 0.016), and the presence of diffuse edema (p = 0.009), were the key anatomical predictors of PAV. Brainstem injuries (p = 0.020) and indicators of diffuse cerebral trauma, such as deep white matter shearing (p = 0.036) and multiple subcortical lesions (p = 0.033), were the principal determinants of 6-month recovery. Inclusion of PAV enhanced the accuracy of prediction models that encompassed a selective combination of clinical and anatomical variables (adjusted R(2) = 0.458, p < 0.001). The two main results of this study are (1) PAV is a sensitive predictor of 6-month clinical outcomes following TBI, and (2) injury to the thalamus is related to impaired PAV. PAV appears best utilized as a functional adjunct to traditional clinical and anatomical predictors.


Assuntos
Ritmo alfa , Lesões Encefálicas/diagnóstico , Eletroencefalografia , Tálamo/lesões , Adolescente , Adulto , Idoso , Lesões Encefálicas/fisiopatologia , Lesões Encefálicas/cirurgia , Descompressão Cirúrgica , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Valor Preditivo dos Testes , Prognóstico , Tálamo/cirurgia , Resultado do Tratamento
11.
IEEE Trans Biomed Eng ; 54(4): 597-610, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17405367

RESUMO

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. Following the offline stage, an online filtering process is performed using a nonlinear Kalman filter (KF)-like state estimator that is equipped with a new way of deriving the Kalman gain satisfying the physiological constraints on the state variables. The proposed method is then validated by comparing different state estimation methods and input/output (I/O) configurations using simulated data. It is also applied to a set of CBFV, ICP and arterial blood pressure (ABP) signal segments from brain injury patients. The results indicated that the proposed constrained nonlinear KF achieved the best performance among the evaluated state estimators and that the state estimator combined with the I/O configuration that has ICP as the measured output can potentially be used to estimate CBFV continuously. Finally, the state estimator combined with the I/O configuration that has both ICP and CBFV as outputs can potentially estimate the lumped cerebral arterial radii, which are not measurable in a typical clinical environment.


Assuntos
Algoritmos , Encéfalo/irrigação sanguínea , Encéfalo/fisiologia , Circulação Cerebrovascular/fisiologia , Pressão Intracraniana/fisiologia , Modelos Cardiovasculares , Modelos Neurológicos , Adaptação Fisiológica/fisiologia , Velocidade do Fluxo Sanguíneo/fisiologia , Pressão Sanguínea/fisiologia , Simulação por Computador , Retroalimentação/fisiologia , Homeostase/fisiologia , Humanos , Modelos Estatísticos , Dinâmica não Linear , Processos Estocásticos
12.
J Cereb Blood Flow Metab ; 37(10): 3278-3299, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28816095

RESUMO

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. We identified new candidates from a TBI CSF proteome by selecting trauma-released, astrocyte-enriched proteins including aldolase C (ALDOC), its 38kD breakdown product (BDP), brain lipid binding protein (BLBP), astrocytic phosphoprotein (PEA15), glutamine synthetase (GS) and new 18-25kD-GFAP-BDPs. Their levels increased over four orders of magnitude in severe TBI CSF. First post-injury week, ALDOC levels were markedly high and stable. Short-lived BLBP and PEA15 related to injury progression. ALDOC, BLBP and PEA15 appeared hyper-acutely and were similarly robust in severe and mild TBI blood; 25kD-GFAP-BDP appeared overnight after TBI and was rarely present after mild TBI. Using a human culture trauma model, we investigated biomarker kinetics. Wounded (mechanoporated) astrocytes released ALDOC, BLBP and PEA15 acutely. Delayed cell death corresponded with GFAP release and proteolysis into small GFAP-BDPs. Associating biomarkers with cellular injury stages produced astroglial injury-defined (AID) biomarkers that facilitate TBI assessment, as neurological deficits are rooted not only in death of CNS cells, but also in their functional compromise.


Assuntos
Astrócitos/patologia , Biomarcadores/análise , Lesões Encefálicas Traumáticas/líquido cefalorraquidiano , Proteínas Reguladoras de Apoptose , Astrócitos/química , Concussão Encefálica , Lesões Encefálicas Traumáticas/diagnóstico , Células Cultivadas , Proteína 7 de Ligação a Ácidos Graxos/sangue , Frutose-Bifosfato Aldolase/sangue , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/sangue , Cinética , Fosfoproteínas/sangue , Proteoma/análise , Proteínas Supressoras de Tumor/sangue
13.
IEEE Trans Biomed Eng ; 53(2): 195-209, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16485748

RESUMO

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. The extension of the established block computation method of C measure to an adaptive one was achieved. This new algorithm was then applied to study the C evolution using brain injury patients data from a hyperventilation study and two propofol studies. Nonlinearity has not been detected for all the fifteen recordings, neither has nonlinear dependency between CBFV and ABP. However, their presences in some of the signal segments justified the adoption of a nonlinear measure of dependency capable of characterizing both linear and nonlinear correlations for inferring autoregulation status. C measure started to decrease with the introduction of hypocapnia state indicating that hyperventilation may reduce the dependency of CBFV on ABP fluctuations. On the other hand, complex patterns of C measure evolution were observed among 14 cases of propofol data indicating a nontrivial effect of propofol on the dependency of CBFV on ABP.


Assuntos
Algoritmos , Encéfalo/irrigação sanguínea , Encéfalo/fisiologia , Circulação Cerebrovascular/fisiologia , Pressão Intracraniana/fisiologia , Modelos Cardiovasculares , Modelos Neurológicos , Adaptação Fisiológica/fisiologia , Velocidade do Fluxo Sanguíneo/fisiologia , Pressão Sanguínea/fisiologia , Simulação por Computador , Retroalimentação/fisiologia , Homeostase/fisiologia , Humanos , Modelos Estatísticos , Dinâmica não Linear , Processos Estocásticos
14.
Neurosurg Clin N Am ; 27(4): 465-72, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27637396

RESUMO

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. Future metabolomics-based studies focused on the diagnoses, prognoses, and treatment effects need to be conducted across all types of traumatic brain injury.


Assuntos
Lesões Encefálicas Traumáticas/metabolismo , Metabolômica , Pesquisa , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Cromatografia Gasosa , Cromatografia Líquida , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas
15.
J Cereb Blood Flow Metab ; 36(9): 1603-13, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26661201

RESUMO

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. Ketones decrease oxidative stress, increase antioxidants and scavenge free radicals. It is hypothesized that ketogenic diet (KD) will decrease post-TBI oxidative stress and improve mitochondria. Postnatal day 35 (PND35) male rats were given sham or controlled cortical impact (CCI) injury and placed on standard (STD) or KD. Ipsilateral cortex homogenates and mitochondria were assayed for markers of oxidative stress, antioxidant expression and mitochondrial function. Oxidative stress was significantly increased at 6 and 24 h post-injury and attenuated by KD while inducing protein expression of antioxidants, NAD(P)H dehydrogenase quinone 1 (NQO1) and superoxide dismutase (SOD1/2). Complex I activity was inhibited in STD and KD groups at 6 h and normalized by 24 h. KD significantly improved Complex II-III activity that was reduced in STD at 6 h. Activity remained reduced at 24 h in STD and unchanged in KD animals. These results strongly suggest that ketones improve post-TBI cerebral metabolism by providing alternative substrates and through antioxidant properties, preventing oxidative stress-mediated mitochondrial dysfunction.


Assuntos
Lesões Encefálicas/dietoterapia , Dieta Cetogênica , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Complexo II de Transporte de Elétrons/metabolismo , Estresse Oxidativo , Animais , Antioxidantes/análise , Lesões Encefálicas/metabolismo , Radicais Livres/análise , Cetonas/metabolismo , Masculino , Mitocôndrias/metabolismo , Ratos , Fatores de Tempo
16.
Brain Inform ; 3: 1-15, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27034916

RESUMO

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. Conventional region-of-interest (ROI) analysis based on manual labeling of brain regions is time-consuming and the results could be inconsistent within and among investigators. In this study, we propose a workflow solution framework that combined the use of non-linear spatial normalization of structural brain images and template-based anatomical labeling to automate the ROI analysis process. The proposed workflow solution is applied to dynamic PET scanning with 15O-water (0-10 min) and 18F-FDDNP (0-6 min) for measuring cerebral blood flow in patients with TBI.

17.
Stroke ; 36(9): e83-99, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16100027

RESUMO

BACKGROUND AND PURPOSE: Numerous imaging techniques have been developed and applied to evaluate brain hemodynamics. Among these are positron emission tomography, single photon emission computed tomography, Xenon-enhanced computed tomography, dynamic perfusion computed tomography, MRI dynamic susceptibility contrast, arterial spin labeling, and Doppler ultrasound. These techniques give similar information about brain hemodynamics in the form of parameters such as cerebral blood flow or cerebral blood volume. All of them are used to characterize the same types of pathological conditions. However, each technique has its own advantages and drawbacks. SUMMARY OF REVIEW: This article addresses the main imaging techniques dedicated to brain hemodynamics. It represents a comparative overview established by consensus among specialists of the various techniques. CONCLUSIONS: For clinicians, this article should offer a clearer picture of the pros and cons of currently available brain perfusion imaging techniques and assist them in choosing the proper method for every specific clinical setting.


Assuntos
Encéfalo/patologia , Angiografia por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia Doppler/métodos , Idoso , Encéfalo/irrigação sanguínea , Calibragem , Circulação Cerebrovascular , Meios de Contraste/farmacologia , Feminino , Hemodinâmica , Humanos , Angiografia por Ressonância Magnética/instrumentação , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/instrumentação , Marcadores de Spin , Tomografia Computadorizada de Emissão de Fóton Único/instrumentação , Tomografia Computadorizada por Raios X/instrumentação , Ultrassonografia Doppler/instrumentação , Xenônio/farmacologia
18.
J Cereb Blood Flow Metab ; 25(6): 763-74, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15716852

RESUMO

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.


Assuntos
Lesões Encefálicas/diagnóstico por imagem , Lesões Encefálicas/metabolismo , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/metabolismo , Microdiálise/métodos , Tomografia por Emissão de Pósitrons/métodos , Doença Aguda , Adolescente , Adulto , Lesões Encefálicas/epidemiologia , Isquemia Encefálica/epidemiologia , Glucose/metabolismo , Humanos , Incidência , Ácido Láctico/metabolismo , Estudos Longitudinais , Microdiálise/normas , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/normas , Estudos Prospectivos , Ácido Pirúvico/metabolismo , Reprodutibilidade dos Testes
19.
J Neurotrauma ; 22(9): 955-65, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16156711

RESUMO

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 +/- 3.2) were prospectively and daily evaluated. Global CBF, cerebral metabolic rates of oxygen (CMRO2), glucose (CMRGlc), and lactate (CMRLct) were calculated using arterial jugular differences. In all patients, CBF was moderately decreased during the first 24 h in comparison with normal subjects although this relative oligemia was more pronounced in patients with poor outcome (p = 0.0007). Both CMRO2 and CMRGlc were significantly depressed and correlated to outcome (p < 0.0001, p = 0.0088). CMRLct analysis revealed positive values (lactate uptake) during the first 48 h, especially in patients with favorable outcome. Both CMRO2 and CMRLct correlated with GCS (p = 0.0001, p = 0.0205). CMRLct levels showed an opposite correlation with CBF in patients with favorable and poor outcome. In the former group, correlation analysis exhibited a negative slope with evidence for increasing lactate uptake associated with lower CBF values (r = -0.1940, p = 0.0242). On the contrary, in patients with adverse outcome, CMRLct values demonstrated a weak though opposite correlation with CBF (r = 0.0942, p = 0.2733). The present data emphasize the clinical significance of monitoring of cerebral blood flow and metabolism in TBI and provide evidence for metabolic coupling between astrocytes and neurons.


Assuntos
Lesões Encefálicas/fisiopatologia , Encéfalo/metabolismo , Circulação Cerebrovascular/fisiologia , Adulto , Glucose/metabolismo , Humanos , Ácido Láctico/metabolismo , Consumo de Oxigênio/fisiologia , Recuperação de Função Fisiológica
20.
J Neurosurg ; 103(5): 812-24, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16304984

RESUMO

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 > 3.4); D (VBA > 90 cm/second); and E (SI in the posterior circulation > 2.5). Criteria C and E were considered to represent hemodynamically significant vasospasm. Mixed-effects spline models were used to analyze the data of multiple measurements with an inconsistent sampling rate. Overall 45.2% of the patients demonstrated at least one criterion for vasospasm. The patients in whom vasospasm developed were significantly younger and had lower Glasgow Coma Scale scores on admission. The normalized cumulative incidences were 36.9 and 36.2% for patients with Criteria A and B, respectively. Hemodynamically significant vasospasm in the anterior circulation (Criterion C) was found in 44.6% of the patients, whereas vasospasm in the BA-Criterion D or E-was found in only 19 and 22.5% of the patients, respectively. The most common day of onset for Criteria A, B, D, and E was postinjury Day 2. The highest risk of developing hemodynamically significant vasospasm in the anterior circulation was found on Day 3. The daily prevalence of vasospasm in patients in the intensive care unit was 30% from postinjury Day 2 to Day 13. Vasospasm resolved after a duration of 5 days in 50% of the patients with Criterion A or B and after a period of 3.5 days in 50% of those patients with Criterion D or E. Hemodynamically significant vasospasm in the anterior circulation resolved after 2.5 days in 50% of the patients. The time course of that vasospasm was primarily determined by a decrease in CBF. CONCLUSIONS: The incidence of vasospasm after TBI is similar to that following aneurysmal subarachnoid hemorrhage. Because vasospasm is a significant event in a high proportion of patients after severe head injury, close TCD and CBF monitoring is recommended for the treatment of such patients.


Assuntos
Traumatismos Craniocerebrais/diagnóstico por imagem , Traumatismos Craniocerebrais/epidemiologia , Índice de Gravidade de Doença , Vasoespasmo Intracraniano/diagnóstico por imagem , Vasoespasmo Intracraniano/epidemiologia , Adulto , Artéria Cerebral Anterior , Circulação Cerebrovascular , Traumatismos Craniocerebrais/fisiopatologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Posterior , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Fatores de Risco , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/epidemiologia , Hemorragia Subaracnóidea/fisiopatologia , Ultrassonografia Doppler Transcraniana , Vasoespasmo Intracraniano/fisiopatologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA