Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 26
Filtrar
1.
J Head Trauma Rehabil ; 39(5): E381-E392, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38453632

RESUMO

OBJECTIVES: People may experience a myriad of symptoms after mild traumatic brain injury (mTBI), but the relationship between symptoms and objective assessments is poorly characterized. This study sought to investigate the association between symptoms, resting heart rate (HR), and exercise tolerance in individuals following mTBI, with a secondary aim to examine the relationship between symptom-based clinical profiles and recovery. METHODS: Prospective observational study of adults aged 18 to 65 years who had sustained mTBI within the previous 7 days. Symptoms were assessed using the Post-Concussion Symptom Scale, HR was measured at rest, and exercise tolerance was assessed using the Buffalo Concussion Bike Test. Symptom burden and symptom-based clinical profiles were examined with respect to exercise tolerance and resting HR. RESULTS: Data from 32 participants were assessed (mean age 36.5 ± 12.6 years, 41% female, 5.7 ± 1.1 days since injury). Symptom burden (number of symptoms and symptom severity) was significantly associated with exercise intolerance ( P = .002 and P = .025, respectively). Physiological and vestibular-ocular clinical profile composite groups were associated with exercise tolerance ( P = .001 and P = .014, respectively), with individuals who were exercise intolerant having a higher mean number of symptoms in each profile than those who were exercise tolerant. Mood-related and autonomic clinical profiles were associated with a higher resting HR (>80 bpm) ( P = .048 and P = .028, respectively), suggesting altered autonomic response for participants with symptoms relating to this profile. After adjusting for age and mechanism of injury (sports- or non-sports-related), having a higher mood-related clinical profile was associated with persisting symptoms at 3 months postinjury (adjusted odds ratio = 2.08; 95% CI, 1.11-3.90; P = .013). CONCLUSION: Symptom-based clinical profiles, in conjunction with objective measures such as resting HR and exercise tolerance, are important components of clinical care for those having sustained mTBI. These results provide preliminary support for the concept that specific symptoms are indicative of autonomic dysfunction following mTBI.


Assuntos
Concussão Encefálica , Tolerância ao Exercício , Frequência Cardíaca , Humanos , Feminino , Masculino , Adulto , Frequência Cardíaca/fisiologia , Estudos Prospectivos , Concussão Encefálica/fisiopatologia , Concussão Encefálica/complicações , Pessoa de Meia-Idade , Tolerância ao Exercício/fisiologia , Adulto Jovem , Síndrome Pós-Concussão/fisiopatologia , Adolescente , Idoso , Teste de Esforço
2.
J Neuroinflammation ; 20(1): 77, 2023 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-36935484

RESUMO

Traumatic brain injury is common, and often results in debilitating consequences. Even mild traumatic brain injury leaves approximately 20% of patients with symptoms that persist for months. Despite great clinical need there are currently no approved pharmaceutical interventions that improve outcomes after traumatic brain injury. Increased understanding of the endocannabinoid system in health and disease has accompanied growing evidence for therapeutic benefits of Cannabis sativa. This has driven research of Cannabis' active chemical constituents (phytocannabinoids), alongside endogenous and synthetic counterparts, collectively known as cannabinoids. Also of therapeutic interest are other Cannabis constituents, such as terpenes. Cannabinoids interact with neurons, microglia, and astrocytes, and exert anti-inflammatory and neuroprotective effects which are highly desirable for the management of traumatic brain injury. In this review, we comprehensively appraised the relevant scientific literature, where major and minor phytocannabinoids, terpenes, synthetic cannabinoids, and endogenous cannabinoids were assessed in TBI, or other neurological conditions with pathology and symptomology relevant to TBI, as well as recent studies in preclinical TBI models and clinical TBI populations.


Assuntos
Concussão Encefálica , Canabinoides , Cannabis , Humanos , Canabinoides/farmacologia , Canabinoides/uso terapêutico , Cannabis/química , Terpenos/uso terapêutico , Agonistas de Receptores de Canabinoides
3.
Gerontology ; 69(2): 201-211, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36174542

RESUMO

INTRODUCTION: Evidence suggests that maintaining a higher level of cardiorespiratory fitness (CRF) later in life can offer some protection against brain volume loss as we age. By contrast, mild traumatic brain injury (mTBI) could accelerate age-related cortical atrophy. The current study sought to examine whether variations in the CRF level modified the association between mTBI history and brain volumetric measures in a sample of older adults. METHODS: Seventy-nine community-dwelling older adults (mean age 68.7 ± 4.3 years, 54.4% female) were assessed for their mTBI history: 25 participants (32%) reported sustaining at least one lifetime mTBI. Participants also underwent a CRF assessment and magnetic resonance imaging (MRI) to obtain global and region-of-interest volumes. RESULTS: Analysis of covariance, controlling for age, sex, education, and apolipoprotein (APOE) ε4 allele carriage, revealed that participants with a history of mTBI had a significantly larger total mean grey matter volume (582.21 ± 12.46 cm3) in comparison to participants with no mTBI history (571.08 ± 17.21 cm3, p = 0.01 after correction for multiple comparisons). However, no differences between groups based on mTBI history were found for total white matter volume or in any other cortical or subcortical structures examined. A subsequent moderation analysis found that CRF was predominantly non-influential on the association between mTBI history and the MRI-quantified measures of brain volume. CONCLUSION: While unexpected, the findings suggest that a history of mTBI can lead to grey matter alterations in the ageing brain. However, concurrent variations in the CRF level did not influence the differences in brain volume found based on mTBI exposure status.


Assuntos
Concussão Encefálica , Aptidão Cardiorrespiratória , Substância Branca , Humanos , Feminino , Idoso , Masculino , Concussão Encefálica/diagnóstico por imagem , Concussão Encefálica/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Envelhecimento , Substância Branca/patologia , Imageamento por Ressonância Magnética/métodos
4.
Int J Mol Sci ; 24(7)2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-37047768

RESUMO

Blast-induced neurotrauma (BINT) frequently occurs during military training and deployment and has been linked to long-term neuropsychological and neurocognitive changes, and changes in brain structure. As military personnel experience frequent exposures to stress, BINT may negatively influence stress coping abilities. This study aimed to determine the effects of BINT on gray matter volume and hormonal alteration. Participants were Canadian Armed Forces personnel and veterans with a history of BINT (n = 12), and first responder controls (n = 8), recruited due to their characteristic occupational stress professions. Whole saliva was collected via passive drool on the morning of testing and analyzed for testosterone (pg/mL), cortisol (µg/dL), and testosterone/cortisol (T/C) ratio. Voxel-based morphometry was performed to compare gray matter (GM) volume, alongside measurement of cortical thickness and subcortical volumes. Saliva analyses revealed distinct alterations following BINT, with significantly elevated testosterone and T/C ratio. Widespread and largely symmetric loci of reduced GM were found specific to BINT, particularly in the temporal gyrus, precuneus, and thalamus. These findings suggest that BINT affects hypothalamic-pituitary-adrenal and -gonadal axis function, and causes anatomically-specific GM loss, which were not observed in a comparator group with similar occupational stressors. These findings support BINT as a unique injury with distinct structural and endocrine consequences.


Assuntos
Traumatismos por Explosões , Humanos , Hidrocortisona , Substância Cinzenta , Canadá , Encéfalo , Imageamento por Ressonância Magnética
5.
Int J Mol Sci ; 24(4)2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36834755

RESUMO

Adolescence is a critical period of postnatal development characterized by social, emotional, and cognitive changes. These changes are increasingly understood to depend on white matter development. White matter is highly vulnerable to the effects of injury, including secondary degeneration in regions adjacent to the primary injury site which alters the myelin ultrastructure. However, the impact of such alterations on adolescent white matter maturation is yet to be investigated. To address this, female piebald-virol-glaxo rats underwent partial transection of the optic nerve during early adolescence (postnatal day (PND) 56) with tissue collection two weeks (PND 70) or three months later (PND 140). Axons and myelin in the transmission electron micrographs of tissue adjacent to the injury were classified and measured based on the appearance of the myelin laminae. Injury in adolescence impaired the myelin structure in adulthood, resulting in a lower percentage of axons with compact myelin and a higher percentage of axons with severe myelin decompaction. Myelin thickness did not increase as expected into adulthood after injury and the relationship between the axon diameter and myelin thickness in adulthood was altered. Notably, dysmyelination was not observed 2 weeks postinjury. In conclusion, injury in adolescence altered the developmental trajectory, resulting in impaired myelin maturation when assessed at the ultrastructural level in adulthood.


Assuntos
Doenças Desmielinizantes , Traumatismos do Nervo Óptico , Feminino , Animais , Ratos , Bainha de Mielina/fisiologia , Axônios/ultraestrutura , Nervo Óptico/fisiologia , Traumatismos do Nervo Óptico/complicações , Doenças Desmielinizantes/complicações
6.
Acta Neuropathol ; 137(5): 731-755, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30535946

RESUMO

This review recounts the definitions and research evidence supporting the multifaceted roles of neuroinflammation in the injured brain following trauma. We summarise the literature fluctuating from the protective and detrimental properties that cytokines, leukocytes and glial cells play in the acute and chronic stages of TBI, including the intrinsic factors that influence cytokine responses and microglial functions relative to genetics, sex, and age. We elaborate on the pros and cons that cytokines, chemokines, and microglia play in brain repair, specifically neurogenesis, and how such conflicting roles may be harnessed therapeutically to sustain the survival of new neurons. With a brief review of the clinical and experimental findings demonstrating early and chronic inflammation impacts on outcomes, we focus on the clinical conditions that may be amplified by neuroinflammation, ranging from acute seizures to chronic epilepsy, neuroendocrine dysfunction, dementia, depression, post-traumatic stress disorder and chronic traumatic encephalopathy. Finally, we provide an overview of the therapeutic agents that have been tested to reduce inflammation-driven secondary pathological cascades and speculate the future promise of alternative drugs.


Assuntos
Lesões Encefálicas Traumáticas/fisiopatologia , Inflamação/fisiopatologia , Animais , Lesões Encefálicas Traumáticas/epidemiologia , Lesões Encefálicas Traumáticas/terapia , Humanos , Inflamação/epidemiologia , Inflamação/terapia , Neuroimunomodulação
7.
Crit Care Med ; 46(4): 554-561, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29278529

RESUMO

OBJECTIVE: To determine profiles of serum ubiquitin carboxy-terminal hydrolase L1 and phosphorylated neurofilament heavy-chain, examine whether erythropoietin administration reduce their concentrations, and whether biomarkers discriminate between erythropoietin and placebo treatment groups. DESIGN: Single-center, prospective observational study. SETTING: A sub-study of the erythropoietin-traumatic brain injury clinical trial, conducted at the Alfred Hospital, Melbourne, Australia. PATIENTS: Forty-four patients with moderate-to-severe traumatic brain injury. INTERVENTIONS: Epoetin alfa 40,000 IU or 1 mL sodium chloride 0.9 as subcutaneous injection within 24 hours of traumatic brain injury. MEASUREMENTS AND MAIN RESULTS: Ubiquitin carboxy-terminal hydrolase L1, phosphorylated neurofilament heavy-chain, and erythropoietin concentrations were measured in serum by enzyme-linked immunosorbent assay from D0 (within 24 hr of injury, prior to erythropoietin/vehicle administration) to D5. Biomarker concentrations were compared between injury severities, diffuse versus focal traumatic brain injury and erythropoietin or placebo treatment groups. Ubiquitin carboxy-terminal hydrolase L1 peaked at 146.0 ng/mL on D0, significantly decreased to 84.30 ng/mL on D1, and declined thereafter. Phosphorylated neurofilament heavy-chain levels were lowest at D0 and peaked on D5 at 157.9 ng/mL. D0 ubiquitin carboxy-terminal hydrolase L1 concentrations were higher in diffuse traumatic brain injury. Peak phosphorylated neurofilament heavy-chain levels on D3 and D4 correlated with Glasgow Outcome Score-Extended, predicting poor outcome. Erythropoietin did not reduce concentrations of ubiquitin carboxy-terminal hydrolase L1 or phosphorylated neurofilament heavy-chain. CONCLUSIONS: Serum ubiquitin carboxy-terminal hydrolase L1 and phosphorylated neurofilament heavy-chain increase after traumatic brain injury reflecting early neuronal and progressive axonal injury. Consistent with lack of improved outcome in traumatic brain injury patients treated with erythropoietin, biomarker concentrations and profiles were not affected by erythropoietin. Pharmacokinetics of erythropoietin suggest that the dose given was possibly too low to exert neuroprotection.


Assuntos
Lesões Encefálicas Traumáticas/tratamento farmacológico , Epoetina alfa/farmacologia , Epoetina alfa/uso terapêutico , Eritropoetina/sangue , Proteínas de Neurofilamentos/sangue , Ubiquitina Tiolesterase/efeitos dos fármacos , Adulto , Austrália , Biomarcadores , Método Duplo-Cego , Ensaio de Imunoadsorção Enzimática , Epoetina alfa/farmacocinética , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ubiquitina Tiolesterase/sangue
8.
J Trauma Stress ; 31(1): 89-101, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29465774

RESUMO

Adaptability to stress is governed by innate resilience, comprised of complex neuroendocrine and immune mechanisms alongside inherited or learned behavioral traits. Based on their capacity to adapt, some people thrive in stressful situations, whereas others experience maladaptation. In our study, we used state-of-the-art tools to assess the resilience level in individuals, as well as their susceptibility to developing military stress-induced behavioral and cognitive deficits. To address this complex question, we tested Canadian Armed Forces (CAF) personnel in three distinct stress environments (baselines): during predeployment training, deployment in Afghanistan, and readjustment upon return to Canada. Our comprehensive outcome measures included psychometric tests, saliva biomarkers, and computerized cognitive tests that used the Cambridge Neuropsychological Automated Test Battery. Participants were categorized based on initial biomarker measurements as being at low-, moderate-, or high stress-maladaptation risk. Biomarkers showed significant changes (ds = 0.56 to 2.44) between baselines, calculated as "delta" changes. Participants at low stress-maladaptation risk demonstrated minimal changes, whereas those at high stress-maladaptation risk showed significant biomarker variations. The psychometric patterns and cognitive functions were likewise affected across baselines, suggesting that the panel of saliva stress biomarkers could be a useful tool for determining the risk of stress maladaptation that can cause psychological and cognitive decline.


Assuntos
Adaptação Psicológica/fisiologia , Militares/psicologia , Estresse Ocupacional/psicologia , Resiliência Psicológica , Adulto , Campanha Afegã de 2001- , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Canadá , Cromogranina A/metabolismo , Transtornos Cognitivos/etiologia , Suscetibilidade a Doenças/psicologia , Feminino , Humanos , Hidrocortisona/metabolismo , Masculino , Transtornos Mentais/etiologia , Testes Neuropsicológicos , Estresse Ocupacional/metabolismo , Escalas de Graduação Psiquiátrica , Saliva/metabolismo , Testosterona/metabolismo , alfa-Amilases/metabolismo
9.
J Neurotrauma ; 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39096132

RESUMO

Mild traumatic brain injury (mTBI) is the most common form of traumatic brain injury. Post-concussive symptoms typically resolve after a few weeks although up to 20% of people experience these symptoms for >3 months, termed persistent post-concussive symptoms (PPCS). Subtle white matter (WM) microstructural damage is thought to underlie neurological and cognitive deficits experienced post-mTBI. Evidence suggests that diffusion magnetic resonance imaging (dMRI) and blood-based biomarkers could be used as surrogate markers of WM organization. We conducted a scoping review according to PRISMA-ScR guidelines, aiming to collate evidence for the use of dMRI and/or blood-based biomarkers of WM organization, in mTBI and PPCS, and document relationships between WM biomarkers and symptoms. We focused specifically on biomarkers of axonal or myelin integrity post-mTBI. Biomarkers excluded from this review therefore included the following: astroglial, perivascular, endothelial, and inflammatory markers. A literature search performed across four databases, EMBASE, Scopus, Google Scholar, and ProQuest, identified 100 records: 68 analyzed dMRI, 28 assessed blood-based biomarkers, and 4 used both. Blood biomarker studies commonly assessed axonal cytoskeleton proteins (i.e., tau); dMRI studies assessed measures of WM organization (i.e., fractional anisotropy). Significant biomarker alterations were frequently associated with heightened symptom burden and prolonged recovery time post-injury. These data suggest that dMRI and blood-based biomarkers may be useful proxies of WM organization, although few studies assessed these complementary measures in parallel, and the relationship between modalities remains unclear. Further studies are warranted to assess the benefit of a combined biomarker approach in evaluating alterations to WM organization after mTBI.

10.
Neurotrauma Rep ; 5(1): 424-447, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660461

RESUMO

The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to develop a health informatics approach to collect data predictive of outcomes for persons with moderate-severe TBI across Australia. Central to this approach is a data dictionary; however, no systematic reviews of methods to define and develop data dictionaries exist to-date. This rapid systematic review aimed to identify and characterize methods for designing data dictionaries to collect outcomes or variables in persons with neurological conditions. Database searches were conducted from inception through October 2021. Records were screened in two stages against set criteria to identify methods to define data dictionaries for neurological conditions (International Classification of Diseases, 11th Revision: 08, 22, and 23). Standardized data were extracted. Processes were checked at each stage by independent review of a random 25% of records. Consensus was reached through discussion where necessary. Thirty-nine initiatives were identified across 29 neurological conditions. No single established or recommended method for defining a data dictionary was identified. Nine initiatives conducted systematic reviews to collate information before implementing a consensus process. Thirty-seven initiatives consulted with end-users. Methods of consultation were "roundtable" discussion (n = 30); with facilitation (n = 16); that was iterative (n = 27); and frequently conducted in-person (n = 27). Researcher stakeholders were involved in all initiatives and clinicians in 25. Importantly, only six initiatives involved persons with lived experience of TBI and four involved carers. Methods for defining data dictionaries were variable and reporting is sparse. Our findings are instructive for AUS-TBI and can be used to further development of methods for defining data dictionaries.

11.
J Neurotrauma ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38117144

RESUMO

In this series of eight articles, the Australian Traumatic Brain Injury Initiative (AUS-TBI) consortium describes the Australian approach used to select the common data elements collected acutely that have been shown to predict outcome following moderate-severe traumatic brain injury (TBI) across the lifespan. This article presents the unified single data dictionary, together with additional measures chosen to facilitate comparative effectiveness research and data linkage. Consultations with the AUS-TBI Lived Experience Expert Group provided insights on the merits and considerations regarding data elements for some of the study areas, as well as more general principles to guide the collection of data and the selection of meaningful measures. These are presented as a series of guiding principles and themes. The AUS-TBI Aboriginal and Torres Strait Islander Advisory Group identified a number of key points and considerations for the project approach specific to Aboriginal and Torres Strait Islander peoples, including key issues of data sovereignty and community involvement. These are outlined in the form of principles to guide selection of appropriate methodologies, data management, and governance. Implementation of the AUS-TBI approach aims to maximize ongoing data collection and linkage, to facilitate personalization of care and improved outcomes for people who experience moderate-severe TBI.

12.
J Neurotrauma ; 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38115587

RESUMO

The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to co-design a data resource to predict outcomes for people with moderate-severe traumatic brain injury (TBI) across Australia. Fundamental to this resource is the data dictionary, which is an ontology of data items. Here, we report the systematic review and consensus process for inclusion of biological markers in the data dictionary. Standardized database searches were implemented from inception through April 2022. English-language studies evaluating association between a fluid, tissue, or imaging marker and any clinical outcome in at least 10 patients with moderate-severe TBI were included. Records were screened using a prioritization algorithm and saturation threshold in Research Screener. Full-length records were then screened in Covidence. A pre-defined algorithm was used to assign a judgement of predictive value to each observed association, and high-value predictors were discussed in a consensus process. Searches retrieved 106,593 records; 1,417 full-length records were screened, resulting in 546 included records. Two hundred thirty-nine individual markers were extracted, evaluated against 101 outcomes. Forty-one markers were judged to be high-value predictors of 15 outcomes. Fluid markers retained following the consensus process included ubiquitin C-terminal hydrolase L1 (UCH-L1), S100, and glial fibrillary acidic protein (GFAP). Imaging markers included computed tomography (CT) scores (e.g., Marshall scores), pathological observations (e.g., hemorrhage, midline shift), and magnetic resonance imaging (MRI) classification (e.g., diffuse axonal injury). Clinical context and time of sampling of potential predictive indicators are important considerations for utility. This systematic review and consensus process has identified fluid and imaging biomarkers with high predictive value of clinical and long-term outcomes following moderate-severe TBI.

13.
J Neuroinflammation ; 10: 156, 2013 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-24344874

RESUMO

BACKGROUND: Diffuse axonal injury is a common consequence of traumatic brain injury (TBI) and often co-occurs with hypoxia, resulting in poor neurological outcome for which there is no current therapy. Here, we investigate the ability of the multifunctional compound erythropoietin (EPO) to provide neuroprotection when administered to rats after diffuse TBI alone or with post-traumatic hypoxia. METHODS: Sprague-Dawley rats were subjected to diffuse traumatic axonal injury (TAI) followed by 30 minutes of hypoxic (Hx, 12% O2) or normoxic ventilation, and were administered recombinant human EPO-α (5000 IU/kg) or saline at 1 and 24 hours post-injury. The parameters examined included: 1) behavioural and cognitive deficit using the Rotarod, open field and novel object recognition tests; 2) axonal pathology (NF-200); 3) callosal degradation (hematoxylin and eosin stain); 3) dendritic loss (MAP2); 4) expression and localisation of the EPO receptor (EpoR); 5) activation/infiltration of microglia/macrophages (CD68) and production of IL-1ß. RESULTS: EPO significantly improved sensorimotor and cognitive recovery when administered to TAI rats with hypoxia (TAI + Hx). A single dose of EPO at 1 hour reduced axonal damage in the white matter of TAI + Hx rats at 1 day by 60% compared to vehicle. MAP2 was decreased in the lateral septal nucleus of TAI + Hx rats; however, EPO prevented this loss, and maintained MAP2 density over time. EPO administration elicited an early enhanced expression of EpoR 1 day after TAI + Hx compared with a 7-day peak in vehicle controls. Furthermore, EPO reduced IL-1ß to sham levels 2 hours after TAI + Hx, concomitant to a decrease in CD68 positive cells at 7 and 14 days. CONCLUSIONS: When administered EPO, TAI + Hx rats had improved behavioural and cognitive performance, attenuated white matter damage, resolution of neuronal damage spanning from the axon to the dendrite, and suppressed neuroinflammation, alongside enhanced expression of EpoR. These data provide compelling evidence of EPO's neuroprotective capability. Few benefits were observed when EPO was administered to TAI rats without hypoxia, indicating that EPO's neuroprotective capacity is bolstered under hypoxic conditions, which may be an important consideration when EPO is employed for neuroprotection in the clinic.


Assuntos
Lesões Encefálicas/patologia , Eritropoetina/farmacologia , Fármacos Neuroprotetores/farmacologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Animais , Axônios/efeitos dos fármacos , Axônios/patologia , Comportamento Animal/efeitos dos fármacos , Lesões Encefálicas/metabolismo , Hipóxia Encefálica/metabolismo , Hipóxia Encefálica/patologia , Imuno-Histoquímica , Inflamação/patologia , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptores da Eritropoetina/metabolismo , Regulação para Cima
14.
Metabolites ; 12(4)2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35448509

RESUMO

Mild traumatic brain injury (mTBI) causes structural, cellular and biochemical alterations which are difficult to detect in the brain and may persist chronically following single or repeated injury. Lipids are abundant in the brain and readily cross the blood-brain barrier, suggesting that lipidomic analysis of blood samples may provide valuable insight into the neuropathological state. This study used liquid chromatography-mass spectrometry (LC-MS) to examine plasma lipid concentrations at 11 days following sham (no injury), one (1×) or two (2×) mTBI in rats. Eighteen lipid species were identified that distinguished between sham, 1× and 2× mTBI. Three distinct patterns were found: (1) lipids that were altered significantly in concentration after either 1× or 2× F mTBI: cholesterol ester CE (14:0) (increased), phosphoserine PS (14:0/18:2) and hexosylceramide HCER (d18:0/26:0) (decreased), phosphoinositol PI(16:0/18:2) (increased with 1×, decreased with 2× mTBI); (2) lipids that were altered in response to 1× mTBI only: free fatty acid FFA (18:3 and 20:3) (increased); (3) lipids that were altered in response to 2× mTBI only: HCER (22:0), phosphoethanolamine PE (P-18:1/20:4 and P-18:0/20:1) (increased), lysophosphatidylethanolamine LPE (20:1), phosphocholine PC (20:0/22:4), PI (18:1/18:2 and 20:0/18:2) (decreased). These findings suggest that increasing numbers of mTBI induce a range of changes dependent upon the lipid species, which likely reflect a balance of damage and reparative responses.

15.
J Neuroinflammation ; 8: 147, 2011 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-22034986

RESUMO

BACKGROUND: The combination of diffuse brain injury with a hypoxic insult is associated with poor outcomes in patients with traumatic brain injury. In this study, we investigated the impact of post-traumatic hypoxia in amplifying secondary brain damage using a rat model of diffuse traumatic axonal injury (TAI). Rats were examined for behavioral and sensorimotor deficits, increased brain production of inflammatory cytokines, formation of cerebral edema, changes in brain metabolism and enlargement of the lateral ventricles. METHODS: Adult male Sprague-Dawley rats were subjected to diffuse TAI using the Marmarou impact-acceleration model. Subsequently, rats underwent a 30-minute period of hypoxic (12% O2/88% N2) or normoxic (22% O2/78% N2) ventilation. Hypoxia-only and sham surgery groups (without TAI) received 30 minutes of hypoxic or normoxic ventilation, respectively. The parameters examined included: 1) behavioural and sensorimotor deficit using the Rotarod, beam walk and adhesive tape removal tests, and voluntary open field exploration behavior; 2) formation of cerebral edema by the wet-dry tissue weight ratio method; 3) enlargement of the lateral ventricles; 4) production of inflammatory cytokines; and 5) real-time brain metabolite changes as assessed by microdialysis technique. RESULTS: TAI rats showed significant deficits in sensorimotor function, and developed substantial edema and ventricular enlargement when compared to shams. The additional hypoxic insult significantly exacerbated behavioural deficits and the cortical production of the pro-inflammatory cytokines IL-6, IL-1ß and TNF but did not further enhance edema. TAI and particularly TAI+Hx rats experienced a substantial metabolic depression with respect to glucose, lactate, and glutamate levels. CONCLUSION: Altogether, aggravated behavioural deficits observed in rats with diffuse TAI combined with hypoxia may be induced by enhanced neuroinflammation, and a prolonged period of metabolic dysfunction.


Assuntos
Lesões Encefálicas , Encéfalo , Encefalite , Hipóxia/metabolismo , Animais , Comportamento Animal/fisiologia , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Lesões Encefálicas/complicações , Lesões Encefálicas/patologia , Lesões Encefálicas/fisiopatologia , Citocinas/metabolismo , Encefalite/etiologia , Encefalite/patologia , Encefalite/fisiopatologia , Glucose/metabolismo , Ácido Glutâmico/metabolismo , Humanos , Lactatos/metabolismo , Masculino , Microdiálise , Testes Neuropsicológicos , Ratos , Ratos Sprague-Dawley
16.
Neuroimage Clin ; 29: 102555, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33461111

RESUMO

OBJECTIVE: Phenylketonuria (PKU) is an autosomal recessive disorder whereby deficiencies in phenylalanine metabolism cause progressive neurological dysfunction. Managing PKU is challenging, with disease monitoring focussed on short-term phenylalanine control rather than measures of neuronal damage. Conventional imaging lacks sensitivity, however diffusion kurtosis imaging (DKI), a new MRI method may reveal subclinical white matter structural changes in PKU. METHODS: This cohort study involved adults with PKU recruited during routine clinical care. MRI, neurocognitive assessment and historical phenylalanine (Phe) levels were collected. A hypothesis-generating case study comparing diet-compliant and non-compliant siblings confirmed that DKI metrics are sensitive to dietary adherence and prompted a candidate metric (Krad/KFA ratio). We then tested this metric in a Replication cohort (PKU = 20; controls = 43). RESULTS: Both siblings scored outside the range of controls for all DKI-based metrics, with severe changes in the periventricular white matter and a gradient of severity toward the cortex. Krad/KFA provided clear separation by diagnosis in the Replication cohort (p < 0.001 in periventricular, deep and pericortical compartments). The ratio also correlated negatively with attention (r = -0.51 & -0.50, p < 0.05) and positively with 3-year mean Phe (r = 0.45 & 0.58, p < 0.01). CONCLUSION: DKI reveals regionally-specific, progressive abnormalities of brain diffusion characteristics in PKU, even in the absence of conspicuous clinical signs or abnormalities on conventional MRI. A DKI-based marker derived from these scores (Krad/KFA ratio) was sensitive to cognitive impairment and PKU control over the medium term and may provide a meaningful subclinical biomarker of end-organ damage.


Assuntos
Fenilcetonúrias , Substância Branca , Adulto , Encéfalo , Estudos de Coortes , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão , Humanos , Fenilcetonúrias/diagnóstico por imagem , Substância Branca/diagnóstico por imagem
17.
Brain Imaging Behav ; 15(3): 1685-1704, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32720180

RESUMO

Sports-related concussion (SRC) is a complex and heterogeneous injury with psychological, cognitive and functional consequences. Advances in diffusion magnetic resonance imaging (dMRI) allow sensitive measurement of white matter pathology post-SRC and may provide insight into injury and recovery. We systematically reviewed and meta-analyzed the literature examining dMRI alongside cognitive, emotional or motor assessments to determine relationships between these analyses. Sixteen studies examining young athletes (n = 6) or retired professionals (n = 10) met the inclusion criteria, with 12 emotional, 10 cognitive and four motor assessments. Studies had heterogeneous methodology, moderate quality and modest sample sizes. Fractional anisotropy (FA) was the most frequent dMRI metric, with SRC-induced changes described most commonly in the frontal lobe and least in the cerebellum and brainstem. There is an emerging complementary role for dMRI as part of a comprehensive assessment battery for SRC. However, larger-scale studies with broader subject populations (specifically, in females and in the 30-45 year age range) are needed to corroborate findings and determine the true diagnostic utility of dMRI post-SRC.


Assuntos
Traumatismos em Atletas , Concussão Encefálica , Traumatismos em Atletas/diagnóstico por imagem , Concussão Encefálica/diagnóstico por imagem , Cognição , Imagem de Difusão por Ressonância Magnética , Emoções , Feminino , Humanos , Imageamento por Ressonância Magnética
18.
Sci Rep ; 11(1): 8861, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33893374

RESUMO

Exposure to repeated concussive traumatic brain injury (TBI) and to blast-induced TBI has been associated with the potential development of the neurodegenerative condition known as chronic traumatic encephalopathy (CTE). CTE is characterized by the accumulation of hyperphosphorylated tau protein, with the resultant tau tangles thought to initiate the cognitive and behavioral manifestations that appear as the condition progresses. However, the mechanisms linking concussive and blast TBI with tau hyperphosphorylation are unknown. Here we show that single moderate TBI, repeated concussive TBI and blast-induced mild TBI all result in hyperphosphorylation of tau via a substance P mediated mechanism. Post-injury administration of a substance P, NK1 receptor antagonist attenuated the injury-induced phosphorylation of tau by modulating the activity of several key kinases including Akt, ERK1/2 and JNK, and was associated with improvement in neurological outcome. We also demonstrate that inhibition of the TRPV1 mechanoreceptor, which is linked to substance P release, attenuated injury-associated tau hyperphosphorylation, but only when it was administered prior to injury. Our results demonstrate that TBI-mediated stimulation of brain mechanoreceptors is associated with substance P release and consequent tau hyperphosphorylation, with administration of an NK1 receptor antagonist attenuating tau phosphorylation and associated neurological deficits. NK1 antagonists may thus represent a pharmacological approach to attenuate the potential development of CTE following concussive and blast TBI.


Assuntos
Traumatismos por Explosões/metabolismo , Encefalopatia Traumática Crônica/metabolismo , Antagonistas dos Receptores de Neurocinina-1/farmacologia , Proteínas tau/metabolismo , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , Ratos , Ratos Sprague-Dawley , Substância P/metabolismo
19.
Sci Rep ; 11(1): 22594, 2021 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-34799634

RESUMO

Cuprizone is a copper-chelating agent that induces pathology similar to that within some multiple sclerosis (MS) lesions. The reliability and reproducibility of cuprizone for inducing demyelinating disease pathology depends on the animals ingesting consistent doses of cuprizone. Cuprizone-containing pelleted feed is a convenient way of delivering cuprizone, but the efficacy of these pellets at inducing demyelination has been questioned. This study compared the degree of demyelinating disease pathology between mice fed cuprizone delivered in pellets to mice fed a powdered cuprizone formulation at an early 3 week demyelinating timepoint. Within rostral corpus callosum, cuprizone pellets were more effective than cuprizone powder at increasing astrogliosis, microglial activation, DNA damage, and decreasing the density of mature oligodendrocytes. However, cuprizone powder demonstrated greater protein nitration relative to controls. Furthermore, mice fed control powder had significantly fewer mature oligodendrocytes than those fed control pellets. In caudal corpus callosum, cuprizone pellets performed better than cuprizone powder relative to controls at increasing astrogliosis, microglial activation, protein nitration, DNA damage, tissue swelling, and reducing the density of mature oligodendrocytes. Importantly, only cuprizone pellets induced detectable demyelination compared to controls. The two feeds had similar effects on oligodendrocyte precursor cell (OPC) dynamics. Taken together, these data suggest that demyelinating disease pathology is modelled more effectively with cuprizone pellets than powder at 3 weeks. Combined with the added convenience, cuprizone pellets are a suitable choice for inducing early demyelinating disease pathology.


Assuntos
Cuprizona/farmacologia , Doenças Desmielinizantes/tratamento farmacológico , Ração Animal , Animais , Astrócitos/metabolismo , Peso Corporal/efeitos dos fármacos , Quelantes/farmacologia , Corpo Caloso/crescimento & desenvolvimento , Dano ao DNA , Modelos Animais de Doenças , Gliose/patologia , Inflamação/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Esclerose Múltipla/tratamento farmacológico , Oligodendroglia/metabolismo , Reprodutibilidade dos Testes
20.
Front Neurol ; 11: 350, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32508733

RESUMO

Objective: Mild traumatic brain injury (mTBI) is associated with depressed mood acutely post-injury, but there is little evidence regarding long-term depression. The aim of this study was to determine the odds ratio (OR) of depression chronically following mTBI. Methods: We searched Medline (PubMed), ProQuest, and Web of Science from date of database creation to January 23, 2019, for eligible studies examining depression at least 6 months post-injury in adult subjects with mTBI of any etiology, including civilians and military. Three authors independently reviewed titles and abstracts for study eligibility. Data were extracted and collated by two investigators. Risk of bias was assessed with the SIGN methodology. Study data were pooled using random-effects meta-analysis. The primary exposure was mTBI, and the primary outcome was depression. Secondary exploratory variables were time of assessment, age at injury, age at assessment, sex, and etiology. Results: We included 47 cross-sectional studies (n = 25,103 mTBI and 29,982 control), 26 cohort studies (n = 70,119 mTBI, 262,034 control), four prospective observational studies (n = 1,058 mTBI and 733 control), two prospective longitudinal studies (n = 119 mTBI, 81 control), two case-control studies (n = 56 mTBI, 56 control), and one randomized controlled trial (n = 252 mTBI, 3,214 control). mTBI was associated with a 3.29-fold increased risk of depression (OR 3.29, 95% CI 2.68-4.03, I 2 = 96%). The OR for depression did not change when subjects were assessed at 6-12 months (OR 2.43, 1.45-4.07), years 1-2 (OR 4.12, 2.10-8.07); 2-10 (OR 3.28, 2.42-4.46), or 10+ (OR 3.42, 1.51-7.77). Similar risk of depression was sustained across different age at injury (<25: OR 2.26, 1.82-2.81; 25-35: OR 4.67, 3.06-7.14; >35: OR 2.69, 1.42-5.10) and different age at assessment (<40 years: OR 3.14, 2.48-3.99; >40 years: OR 4.57, 2.54-8.24). Female sex had a non-significant increase in OR (OR 19.97, 2.39-166.93) compared to male (OR 3.0, 2.33-3.86). mTBI etiology had no impact on depression. Conclusions: Those experiencing mTBI are more than three times more likely to experience depression compared to those without a history of mTBI, and this risk remains decades beyond the mTBI event. Future longitudinal studies are needed to identify and mitigate this risk.

SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa