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1.
J Neurol Sci ; 417: 117087, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32798855

RESUMO

INTRODUCTION: The coronavirus disease 2019 (Covid-19) pandemic has led to challenges in provision of care, clinical assessment and communication with families. The unique considerations associated with evaluation of catastrophic brain injury and death by neurologic criteria in patients with Covid-19 infection have not been examined. METHODS: We describe the evaluation of six patients hospitalized at a health network in New York City in April 2020 who had Covid-19, were comatose and had absent brainstem reflexes. RESULTS: Four males and two females with a median age of 58.5 (IQR 47-68) were evaluated for catastrophic brain injury due to stroke and/or global anoxic injury at a median of 14 days (IQR 13-18) after admission for acute respiratory failure due to Covid-19. All patients had hypotension requiring vasopressors and had been treated with sedative/narcotic drips for ventilator dyssynchrony. Among these patients, 5 had received paralytics. Apnea testing was performed for 1 patient due to the decision to withdraw treatment (n = 2), concern for inability to tolerate testing (n = 2) and observation of spontaneous respirations (n = 1). The apnea test was aborted due to hypoxia and hypotension. After ancillary testing, death was declared in three patients based on neurologic criteria and in three patients based on cardiopulmonary criteria (after withdrawal of support (n = 2) or cardiopulmonary arrest (n = 1)). A family member was able to visit 5/6 patients prior to cardiopulmonary arrest/discontinuation of organ support. CONCLUSION: It is feasible to evaluate patients with catastrophic brain injury and declare brain death despite the Covid-19 pandemic, but this requires unique considerations.


Assuntos
Betacoronavirus , Morte Encefálica/diagnóstico , Lesões Encefálicas/etiologia , Infecções por Coronavirus/complicações , Pandemias , Pneumonia Viral/complicações , Idoso , Apneia/etiologia , Hemorragia Cerebral/etiologia , Contraindicações de Procedimentos , Eletroencefalografia , Feminino , Parada Cardíaca/etiologia , Humanos , Hipóxia Encefálica/etiologia , Masculino , Pessoa de Meia-Idade , Neuroimagem , Exame Neurológico , Relações Profissional-Família , Obtenção de Tecidos e Órgãos , Revelação da Verdade
2.
Life Sci ; 257: 118050, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32634425

RESUMO

BACKGROUND AND PURPOSE: Early brain injury is an essential pathological process after subarachnoid hemorrhage (SAH), with many cell death modalities. Ferroptosis is a newly discovered regulated cell death caused by the iron-dependent accumulation of lipid peroxidation, which can be prevented by glutathione peroxidase 4 (GPX4). Our study aimed to investigate the role of GPX4 in neuronal cell death after experimental SAH. METHODS: In vivo experimental SAH was induced by injecting autologous arterial blood into the prechiasmatic cistern in male Sprague-Dawley rats. Meanwhile, the in vitro SAH model was performed with primary rat cortical neurons cultured in medium containing hemoglobin (Hb). Adenovirus was used to overexpress GPX4 before experimental SAH. GPX4 expression was detected by western blot and immunofluorescence experiments. Malondialdehyde (MDA) was measured to evaluate the level of lipid peroxidation. Nissl staining was employed to assess cell death in vivo, whereas lactate dehydrogenase (LDH) release was used to evaluate cell damage in vitro. The brain water content and neurological deficits were evaluated to determine brain injury. RESULTS: Endogenous GPX4 was mainly expressed in neurons, and its expression decreased at 24 h after experimental SAH. Overexpression of GPX4 significantly reduced lipid peroxidation and cell death in the experimental SAH models both in vivo and in vitro. Moreover, overexpression of GPX4 ameliorated brain edema and neurological deficits at 24 h after SAH. CONCLUSIONS: The decrease of GPX4 expression potentially plays an important role in ferroptosis during early brain injury after SAH. Overexpression of GPX4 has a neuroprotective effect after SAH.


Assuntos
Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/uso terapêutico , Hemorragia Subaracnóidea/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Encéfalo/metabolismo , Edema Encefálico/patologia , Lesões Encefálicas/etiologia , Morte Celular/efeitos dos fármacos , Modelos Animais de Doenças , Ferroptose/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Sprague-Dawley , Hemorragia Subaracnóidea/metabolismo
3.
Neurology ; 95(10): e1372-e1380, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32631921

RESUMO

OBJECTIVE: To examine EEG features of major pathophysiology in children undergoing extracorporeal membrane oxygenation (ECMO). METHODS: This was a single-center, retrospective study of 201 pediatric patients on ECMO, using the first 24 hours of continuous EEG (cEEG) monitoring, collating background activity and electrographic seizures (ES) with imaging, ECMO type, and outcome. RESULTS: Severely abnormal cEEG background occurred in 12% (25/201), and was associated with death (sensitivity 0.23, specificity 0.97). ES occurred in 16% (33/201) within 3.2 (0.6-20.3) hours (median [interquartile range]) of cEEG commencement, and higher ES burden was associated with death. ES was always associated with ipsilateral injury (p = 0.006), but occurred in only one-third of cases with abnormal imaging. In 28 patients with isolated hemisphere lesion, type of arterial ECMO cannulation was associated with side of injury: right carotid cannulation was associated with right hemisphere lesions, and ascending aorta cannulation with left hemisphere lesions (odds ratio, 0.29 [95% confidence interval, 0.08-0.98], p = 0.03). CONCLUSIONS: After starting ECMO, cEEG background activity has the potential to inform prognosis. Type of arterial (carotid vs aortic) ECMO correlates with side of focal cerebral injury, which in ≈33% is associated with presence of ES. We hypothesize that the differential distribution reflects abnormal flow dynamics or embolic injury.


Assuntos
Lesões Encefálicas/etiologia , Lesões Encefálicas/fisiopatologia , Oxigenação por Membrana Extracorpórea/efeitos adversos , Convulsões/etiologia , Convulsões/fisiopatologia , Criança , Pré-Escolar , Eletroencefalografia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos
4.
PLoS One ; 15(6): e0228693, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32574159

RESUMO

BACKGROUND: Sustained inflation (SI) during chest compression (CC = CC+SI) has been recently shown as an alternative method during cardiopulmonary resuscitation in neonates. However, the optimal peak inflation pressure (PIP) of SI during CC+SI to improve ROSC and hemodynamic recovery is unknown. OBJECTIVE: To examine if different PIPs of SI during CC+SI will improve ROSC and hemodynamic recovery in severely asphyxiated piglets. METHODS: Twenty-nine newborn piglets (1-3 days old) were anesthetized, intubated, instrumented and exposed to 30-min normocapnic hypoxia followed by asphyxia. Piglets were randomized into four groups: CC+SI with a PIP of 10 cmH2O (CC+SI_PIP_10, n = 8), a PIP of 20 cmH2O (CC+SI_PIP_20, n = 8), a PIP of 30 cmH2O (CC+SI_PIP_30, n = 8), and a sham-operated control group (n = 5). Heart rate, arterial blood pressure, carotid blood flow, cerebral oxygenation, and respiratory parameters were continuously recorded throughout the experiment. RESULTS: Baseline parameters were similar between all groups. There was no difference in asphyxiation (duration and degree) between intervention groups. PIP correlated positively with tidal volume (VT) and inversely with exhaled CO2 during cardiopulmonary resuscitation. Time to ROSC and rate of ROSC were similar between piglets resuscitated with CC+SI_PIP_10, CC+SI_PIP_20, and CC+SI_PIP_30 cmH2O: median (IQR) 75 (63-193) sec, 94 (78-210) sec, and 85 (70-90) sec; 5/8 (63%), 7/8 (88%), and 3/8 (38%) (p = 0.56 and p = 0.12, respectively). All piglets that achieved ROSC survived to four hours post-resuscitation. Piglets resuscitated with CC+SI_PIP_30 cmH2O exhibited increased concentrations of pro-inflammatory cytokines interleukin-1ß and tumour necrosis factor-α in the frontoparietal cerebral cortex (both p<0.05 vs. sham-operated controls). CONCLUSION: In asphyxiated term newborn piglets resuscitated by CC+SI, the use of different PIPs resulted in similar time to ROSC, but PIP at 30 cmH2O showed a larger VT delivery, lower exhaled CO2 and increased tissue inflammatory markers in the brain.


Assuntos
Asfixia/terapia , Reanimação Cardiopulmonar/efeitos adversos , Insuflação/efeitos adversos , Pressão , Animais , Animais Recém-Nascidos , Lesões Encefálicas/etiologia , Hemodinâmica , Recuperação de Função Fisiológica , Respiração , Suínos
5.
PLoS One ; 15(6): e0234082, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32479533

RESUMO

OBJECTIVES: To investigate whether cerebrospinal fluid levels of neuron-specific enolase (CSF-NSE) during the first 72 hours correlate with other tools used to assess ongoing brain damage, including clinical grading of hypoxic-ischemic encephalopathy (HIE), abnormal patterns in amplitude integrated electroencephalography (aEEG), and magnetic resonance imaging (MRI), as well as with the neurodevelopmental outcomes at two years of age. MATERIAL AND METHODS: Prospective observational study performed in two hospitals between 2009 and 2011. Forty-three infants diagnosed with HIE within 6 hours of life were included. HIE was severe in 20 infants, moderate in 12, and mild in 11. Infants with moderate-to-severe HIE received whole-body cooling. Both the HIE cohort and a control group of 59 infants with suspected infection underwent measurement of CSF-NSE concentrations at between 12 and 72 hours after birth. aEEG monitoring was started at admission and brain MRI was performed within the first 2 weeks. Neurodevelopment was assessed at 24 months. RESULTS: The HIE group showed higher levels of CSF-NSE than the control group: median 70 ng/ml (29; 205) vs 10.6 ng/ml (7.7; 12.9); p <0.001. Median levels of CSF-NSE in infants with severe, moderate, and mild HIE were 220.5 ng/ml (120.5; 368.8), 45.5 ng/ml (26, 75.3), and 26 ng/ml (18, 33), respectively. CSF-NSE levels correlated were significantly higher in infants with seizures, abnormal aEEG, or abnormal MRI, compared to those without abnormalities. Infants with an adverse outcome showed higher CSF-NSE levels than those with normal findings (p<0.001), and the most accurate CSF-NSE cutoff level for predicting adverse outcome in the whole cohort was 108 ng/ml and 50ng/ml in surviving infants. CONCLUSIONS: In the era of hypothermia, CSF-NSE concentrations provides valuable information as a clinical surrogate of the severity of hypoxic-ischemic brain damage, and this information may be predictive of abnormal outcome at two years of age.


Assuntos
Lesões Encefálicas/patologia , Hipotermia Induzida/efeitos adversos , Hipóxia-Isquemia Encefálica/diagnóstico , Fosfopiruvato Hidratase/líquido cefalorraquidiano , Lesões Encefálicas/etiologia , Estudos de Casos e Controles , Eletroencefalografia , Feminino , Idade Gestacional , Humanos , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/terapia , Recém-Nascido , Listeria monocytogenes/patogenicidade , Imagem por Ressonância Magnética , Masculino , Estudos Prospectivos , Convulsões/complicações , Convulsões/diagnóstico , Índice de Gravidade de Doença
6.
Lancet Neurol ; 19(7): 611-622, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32562686

RESUMO

More patients are surviving cardiac arrest than ever before; however, the burden now lies with estimating neurological prognoses in a large number of patients who were initially comatose, in whom the ultimate outcome is unclear. Neurologists, neurointensivists, and clinical neurophysiologists must accurately balance the concern that overly conservative prognostication could leave patients in a severely disabled state, with the possibility that inaccurately pessimistic prognostication could lead to the withdrawal of life-sustaining treatment in patients who might otherwise have a good functional outcome. Prognostic tools have improved greatly, including electrophysiological tests, neuroimaging, and chemical biomarkers. Conclusions about the prognosis should be delayed at least 72 h after arrest to allow for the clearance of sedative drugs. Cognitive impairments, emotional problems, and fatigue are common among patients who have survived cardiac arrest, and often go unrecognised despite being related to caregiver burden and a decreased participation in society. Through simple screening, these problems can be identified, and patients can be provided with adequate information and rehabilitation.


Assuntos
Coma/etiologia , Coma/reabilitação , Parada Cardíaca/complicações , Hipóxia Encefálica/etiologia , Hipóxia Encefálica/reabilitação , Lesões Encefálicas/etiologia , Lesões Encefálicas/reabilitação , Humanos , Prognóstico
7.
N Z Med J ; 133(1515): 97-103, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32438381

RESUMO

The role of the external clinical advisor is critical to the adjudication of complex claims in the processes of the Accident Compensation Corporation (ACC). This is particularly true of claims for treatment injury that occur during birth, which are often very complicated. In most cases external clinical advisors are non-treating doctors, whose opinion strongly guides the hand of ACC. This viewpoint considers the impact of the role of the external clinical advisor by using extracts from an external clinical advisor's report to show how a power imbalance can be enacted in ACC decision making processes. Also considered are the way that the normal checks and balances in the system, particularly those provided by the Health & Disability Commissioner, are bypassed in most cases. Finally, a recommendation is made to potential external clinical advisors to precisely following the standards set by the Medical Council in all cases when writing reports for ACC.


Assuntos
Traumatismos do Nascimento/etiologia , Compensação e Reparação/legislação & jurisprudência , Prova Pericial/normas , Papel do Médico , Lesões Encefálicas/etiologia , Criança , Tomada de Decisões , Prova Pericial/legislação & jurisprudência , Feminino , Transtornos do Crescimento/complicações , Humanos , Doença Iatrogênica , Recém-Nascido , Consentimento Livre e Esclarecido/legislação & jurisprudência , Masculino , Nova Zelândia , Osteocondrodisplasias/complicações , Gravidez , Complicações na Gravidez/etiologia
8.
J Clin Neurosci ; 75: 71-79, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32241644

RESUMO

Gunshot wounds (GSW) are one of the most lethal forms of head trauma. The lack of clear guidelines for civilian GSW complicates surgical management. We aimed to develop a decision-tree algorithm for mortality prediction and report long-term outcomes on survivors based on 15-year data from our level 1 trauma center. We retrospectively reviewed 96 consecutive patients who presented with cerebral GSWs between 2003 and 2018. Clinical information from our trauma database, EMR, and relevant imaging scans was reviewed. A decision-tree model was constructed based on variables showing significant differences between survivors and non-survivors. After excluding patients who died at arrival, 54 patients with radiologically confirmed intracranial injury were included. Compared to survivors (51.9%), non-survivors (48.1%) were significantly more likely to have perforating (entry and exit wound), as opposed to penetrating (entry wound only), injuries. Bi-hemispheric and posterior fossa involvement, cerebral herniation, and intraventricular hemorrhage were more commonly present in non-survivors. Based on the decision-tree, Glasgow Coma Scale (GCS) > 8 and penetrating, uni-hemispheric injury predicted survival. Among patients with GCS ≤ 8 and normal pupillary response, lack of 1) posterior fossa involvement, 2) cerebral herniation, 3) bi-hemispheric injury, and 4) intraventricular hemorrhage, were associated with survival. Favorable long-term outcomes (mean follow-up 34.4 months) were possible for survivors who required neurosurgery and stable patients who were conservatively managed. We applied clinical and radiological characteristics that predicted survival to construct a decision-tree to facilitate surgical decision-making for GSW. Further validation of the algorithm in a large patient setting is recommended.


Assuntos
Algoritmos , Regras de Decisão Clínica , Árvores de Decisões , Ferimentos por Arma de Fogo/mortalidade , Adulto , Lesões Encefálicas/etiologia , Lesões Encefálicas/mortalidade , Lesões Encefálicas/patologia , Traumatismos Craniocerebrais/etiologia , Traumatismos Craniocerebrais/mortalidade , Traumatismos Craniocerebrais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Centros de Traumatologia , Ferimentos por Arma de Fogo/complicações , Ferimentos por Arma de Fogo/patologia
9.
Proc Natl Acad Sci U S A ; 117(15): 8616-8623, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32229571

RESUMO

In the adult brain, vascular endothelial growth factor D (VEGFD) is required for structural integrity of dendrites and cognitive abilities. Alterations of dendritic architectures are hallmarks of many neurologic disorders, including stroke-induced damage caused by toxic extrasynaptic NMDA receptor (eNMDAR) signaling. Here we show that stimulation of eNMDARs causes a rapid shutoff of VEGFD expression, leading to a dramatic loss of dendritic structures. Using the mouse middle cerebral artery occlusion (MCAO) stroke model, we have established the therapeutic potential of recombinant mouse VEGFD delivered intraventricularly to preserve dendritic architecture, reduce stroke-induced brain damage, and facilitate functional recovery. An easy-to-use therapeutic intervention for stroke was developed that uses a new class of VEGFD-derived peptide mimetics and postinjury nose-to-brain delivery.


Assuntos
Lesões Encefálicas/prevenção & controle , Dendritos/fisiologia , Modelos Animais de Doenças , Mucosa Nasal/metabolismo , Fragmentos de Peptídeos/administração & dosagem , Acidente Vascular Cerebral/complicações , Fator D de Crescimento do Endotélio Vascular/administração & dosagem , Administração Intranasal , Animais , Lesões Encefálicas/etiologia , Lesões Encefálicas/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Recuperação de Função Fisiológica
10.
Exp Cell Res ; 389(2): 111912, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32084391

RESUMO

Ischemic stroke leads to neuronal cell death and induces a cascade of inflammatory signals that results in secondary brain damage. Although constant efforts to develop therapeutic strategies and to reveal the molecular mechanism resulting in the physiopathology of this disease, much still remains unclear. Membrane-bound Toll-like receptors (TLRs) and cytosolic nucleotide binding oligomerization domain (NOD)-like receptors (NLRs) are two major families of pattern recognition receptors that initiate pro-inflammatory signaling pathways. In the present study, we explored the role of NLRP10 in regulating inflammatory responses in acute ischemic stroke using the wild type (WT) and NLRP10 knockout (KO) mice by inducing middle cerebral artery occlusion/reperfusion (MCAO) injuries. The study first showed that NLRP10 was over-expressed in the ischemic penumbra of WT mice. Then, the brain infarct volume was significantly decreased, and the moving activity was improved post-MCAO in mice with NLRP10 knockout. Apoptosis was also alleviated by NLRP10-knockout, as evidenced by the decreased number of TUNEL-staining cells. Further, NLRP10 deficiency attenuated the activation of glia cells in hippocampus of mice with MCAO operation. NLRP10 inhibition ameliorated the levels of inflammatory factors in peripheral blood serum and hippocampus of mice after stroke. The activation of toll-like receptor (TLR)-4/nuclear factor-κB (NF-κB) signaling pathways was markedly suppressed by NLRP10 ablation in mice after MCAO treatment. Importantly, inflammasome, including NLRP12, ASC and Caspase-1, induced by MCAO in hippocampus of mice was clearly impeded by the loss of NLRP10. The results above were mainly verified in LPS-incubated astrocytes in the absence of NLRP10. Correspondingly, in LPS-treated astrocytes, NLRP10 knockout-reduced inflammation via impairing TLR-4/NF-κB and NLRP12/ASC/Caspase-1 pathways was evidently restored by over-expressing NLRP10. Therefore, the results above indicated an essential role of NLRP10 in regulating ischemic stroke, presenting NLRP10 as a promising target to protect human against stroke.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Proteínas Reguladoras de Apoptose/fisiologia , Lesões Encefálicas/prevenção & controle , Isquemia Encefálica/complicações , Inflamação/prevenção & controle , Substâncias Protetoras , Traumatismo por Reperfusão/complicações , Acidente Vascular Cerebral/complicações , Animais , Apoptose , Lesões Encefálicas/etiologia , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Caspase 1/metabolismo , Infarto da Artéria Cerebral Média , Inflamassomos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Receptores Toll-Like/metabolismo
11.
Stroke ; 51(3): 967-974, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32019481

RESUMO

Background and Purpose- Microglia are among the first cells to respond to intracerebral hemorrhage (ICH), but the mechanisms that underlie their activity following ICH remain unclear. IL (interleukin)-15 is a proinflammatory cytokine that orchestrates homeostasis and the intensity of the immune response following central nervous system inflammatory events. The goal of this study was to investigate the role of IL-15 in ICH injury. Methods- Using brain slices of patients with ICH, we determined the presence and cellular source of IL-15. A transgenic mouse line with targeted expression of IL-15 in astrocytes was generated to determine the role of astrocytic IL-15 in ICH. The expression of IL-15 was controlled by a glial fibrillary acidic protein promoter (GFAP-IL-15tg). ICH was induced by intraparenchymal injection of collagenase or autologous blood. Results- In patients with ICH and wild-type mice subjected to experimental ICH, we found a significant upregulation of IL-15 in astrocytes. In GFAP-IL-15tg mice, we found that astrocyte-targeted expression of IL-15 exacerbated brain edema and neurological deficits following ICH. This aggravated ICH injury in GFAP-IL-15tg mice is accompanied by increased microglial accumulation in close proximity to astrocytes in perihematomal tissues. Additionally, microglial expression of CD86, IL-1ß, and TNF-α is markedly increased in GFAP-IL-15tg mice following ICH. Furthermore, depletion of microglia using a colony stimulating factor 1 receptor inhibitor diminishes the exacerbation of ICH injury in GFAP-IL-15tg mice. Conclusions- Our findings identify IL-15 as a mediator of the crosstalk between astrocytes and microglia that exacerbates brain injury following ICH.


Assuntos
Astrócitos/imunologia , Lesões Encefálicas/imunologia , Hemorragia Cerebral/imunologia , Interleucina-15/imunologia , Microglia/imunologia , Idoso , Idoso de 80 Anos ou mais , Animais , Astrócitos/patologia , Lesões Encefálicas/etiologia , Lesões Encefálicas/genética , Lesões Encefálicas/patologia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/genética , Hemorragia Cerebral/patologia , Feminino , Humanos , Interleucina-15/genética , Masculino , Camundongos , Camundongos Transgênicos , Microglia/patologia
12.
EBioMedicine ; 52: 102663, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32062359

RESUMO

BACKGROUND: Although thalamic magnetic resonance (MR) spectroscopy (MRS) accurately predicts adverse outcomes after neonatal encephalopathy, its utility in infants without MR visible deep brain nuclei injury is not known. We examined thalamic MRS metabolite perturbations in encephalopathic infants with white matter (WM) injury with or without cortical injury and its associations with adverse outcomes. METHODS: We performed a subgroup analysis of all infants recruited to the MARBLE study with isolated WM or mixed WM/cortical injury, but no visible injury to the basal ganglia/thalamus (BGT) or posterior limb of the internal capsule (PLIC). We used binary logistic regression to examine the association of MRS biomarkers with three outcomes (i) WM injury score (1 vs. 2/3); (ii) cortical injury scores (0/1 vs. 2/3); and (iii) adverse outcomes (defined as death, moderate/severe disability) at two years (yes/no). We also assessed the accuracy of MRS for predicting adverse outcome. FINDINGS: Of the 107 infants included in the analysis, five had adverse outcome. Reduced thalamic N-acetylaspartate concentration [NAA] (odds ratio 0.4 (95% CI 0.18-0.93)) and elevated thalamic Lactate/NAA peak area ratio (odds ratio 3.37 (95% CI 1.45-7.82)) were significantly associated with higher WM injury scores, but not with cortical injury. Thalamic [NAA] (≤5.6 mmol/kg/wet weight) had the best accuracy for predicting adverse outcomes (sensitivity 1.00 (95% CI 0.16-1.00); specificity 0.95 (95% CI 0.84-0.99)). INTERPRETATION: Thalamic NAA is reduced in encephalopathic infants without MR visible deep brain nuclei injury and may be a useful predictor of adverse outcomes. FUNDING: The National Institute for Health Research (NIHR).


Assuntos
Encefalopatias/complicações , Encefalopatias/metabolismo , Lesões Encefálicas/etiologia , Lesões Encefálicas/patologia , Metabolismo Energético , Tálamo/metabolismo , Substância Branca/patologia , Biomarcadores , Encefalopatias/diagnóstico , Lesões Encefálicas/diagnóstico por imagem , Feminino , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido , Imagem por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Sensibilidade e Especificidade , Substância Branca/diagnóstico por imagem
13.
Biochem Biophys Res Commun ; 524(4): 963-969, 2020 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-32059851

RESUMO

Neutrophil gelatinase-associated lipocalin (NGAL) may be a biomarker candidate for brain injury and a novel therapeutic target in ischemic stroke. Epidermal growth factor (EGF) has protective effects on ischemic injury via activating EGF receptor (EGFR). Whether the protection mechanism of activating EGF-EGFR axis against brain injury is involved in regulating NGAL is still unknown. In the present study, we attempted to explore the expression of NGAL in ischemic brain and the effects of EGF on the NGAL expression in a mouse model of middle cerebral artery occlusion (MCAO). Results suggested that the NGAL expression in ischemic brain was markedly increased after cerebral ischemic damage, and specific NGAL-siRNA can attenuate ischemia-triggered infarct volume and neurological deficit. Then, we found that intracerebroventricular EGF treatment may reduce the level of NGAL in ischemic brain, accompanied by functional improvements. Meanwhile, specific JAK2/STAT3 inhibitor AG490 can reverse EGF-induced reduction of NGAL level. Therefore, the elevated NGAL level in ischemic brain may be an important participant in ischemic brain injury. EGF/EGFR activation ameliorated infarct volume of brain tissues and neurological deficit, and the underlying mechanism is involved in regulating the expression of NGAL via the activation of JAK2/STAT3 pathway.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/genética , Fator de Crescimento Epidérmico/uso terapêutico , Lipocalina-2/genética , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/etiologia , Lesões Encefálicas/genética , Isquemia Encefálica/complicações , Regulação para Baixo/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/uso terapêutico
14.
Sci Rep ; 10(1): 614, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31953486

RESUMO

Toxicity to central nervous system tissues is the common side effects for radiotherapy of brain tumor. The radiation toxicity has been thought to be related to the damage of cerebral endothelium. However, because of lacking a suitable high-resolution vivo model, cellular response of cerebral capillaries to radiation remained unclear. Here, we present the flk:eGFP transgenic zebrafish larvae as a feasible model to study the radiation toxicity to cerebral capillary. We showed that, in living zebrafish larvae, radiation could induce acute cerebral capillary shrinkage and blood-flow obstruction, resulting brain hypoxia and glycolysis retardant. Although in vivo neuron damage was also observed after the radiation exposure, further investigation found that they didn't response to the same dosage of radiation in vitro, indicating that radiation induced neuron damage was a secondary-effect of cerebral vascular function damage. In addition, transgenic labeling and qPCR results showed that the radiation-induced acute cerebral endothelial damage was correlated with intensive endothelial autophagy. Different autophagy inhibitors could significantly alleviate the radiation-induced cerebral capillary damage and prolong the survival of zebrafish larvae. Therefore, we showed that radiation could directly damage cerebral capillary, resulting to blood flow deficiency and neuron death, which suggested endothelial autophagy as a potential target for radiation-induced brain toxicity.


Assuntos
Lesões Encefálicas/metabolismo , Endotélio/citologia , Proteínas de Fluorescência Verde/genética , Proteínas Associadas aos Microtúbulos/genética , Neurônios/citologia , Fatores de Transcrição/genética , Proteínas de Peixe-Zebra/genética , Animais , Animais Geneticamente Modificados , Autofagia , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/efeitos da radiação , Lesões Encefálicas/diagnóstico por imagem , Lesões Encefálicas/etiologia , Lesões Encefálicas/genética , Células Cultivadas , Angiografia Cerebral , Técnicas de Cocultura , Irradiação Craniana/efeitos adversos , Modelos Animais de Doenças , Endotélio/efeitos da radiação , Proteínas de Fluorescência Verde/metabolismo , Microscopia Confocal , Proteínas Associadas aos Microtúbulos/metabolismo , Neurônios/efeitos da radiação , Fatores de Transcrição/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/metabolismo
15.
Sci Rep ; 10(1): 1145, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980723

RESUMO

Recurrence of chronic subdural hematoma (CSDH) frequently occurs after surgical evacuation. However, the value of follow-up postoperative imaging and measuring volumetric factors to predict recurrence are still controversial. Herein, we aimed to assess the optimal timing for follow-up referential imaging and the critical depressed brain volume for CSDH recurrence. A total of 291 patients with CSDH who underwent burr hole craniotomy between January 2012 and December 2018 were consecutively enrolled in this study. Patients' medical records and radiologic data were evaluated to predict the recurrence and analyzed using receiver operating characteristics (ROC) and binary logistic regression. Of the 291 patients, 29 (10.0%) showed recurrence after surgical evacuation. Based on ROC analysis, comparisons of depressed brain volume pre-operation, 24 h post-operation, and 7 days post-operation showed that the depressed brain volume at 7 days after surgery featured the largest area under the curve (AUC: 0.768, 95% CI, 0.709-0.811). The cut-off value of the depressed brain volume on postoperative day 7 was 51.6 cm3; this value predicted the recurrence of CSDH with a sensitivity and specificity of 79.3% and 67.9%, respectively. In the multivariate analysis, the depressed brain volume (>50 cm3) at 7 days was the sole significant risk factor related to the recurrence of CSDH in this series (OR: 6.765, 95% CI, 2.551-17.942, p < 0.001). The depressed brain volume > 50 cm3 visualized on CT scans at postoperative 7 day is the critical volume affecting recurrence of CSDHs. This result could be helpful carrying in patients with CSDH to determine the proper postoperative treatment strategy.


Assuntos
Encéfalo/patologia , Drenagem/efeitos adversos , Hematoma Subdural Crônico/cirurgia , Complicações Pós-Operatórias/etiologia , Trepanação/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Área Sob a Curva , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Lesões Encefálicas/etiologia , Lesões Encefálicas/patologia , Criança , Comorbidade , Drenagem/métodos , Feminino , Hematoma Subdural Crônico/diagnóstico por imagem , Humanos , Complicações Intraoperatórias/etiologia , Complicações Intraoperatórias/patologia , Estimativa de Kaplan-Meier , Modelos Logísticos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Tamanho do Órgão , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/uso terapêutico , Período Pós-Operatório , Curva ROC , Recidiva , Fatores de Risco , Tomografia Computadorizada por Raios X , Trepanação/métodos , Adulto Jovem
16.
Br J Neurosurg ; 34(2): 127-134, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31916459

RESUMO

Introduction: A radiological scoring system to define a 'surgically significant' mild Traumatic Brain Injury (TBI) could stratify neurosurgical referrals, and improve communication between referral centres and neurosurgical units, as most referrals are not accepted.Materials and methods: A computed tomography (CT) scoring system based on radiological injuries sustained in a TBI was developed and validated. All neurosurgical referrals to a major tertiary neurosurgery centre in England, UK with a mild TBI (GCS 13-15) during the period of 1st January to 30th October 2017 were scored retrospectively and stratified according to their mean score, and if they were accepted for transfer to the neurosurgical centre. A total of 1248 patients were identified during the study period, with 1144 being included in the final analysis.Results: Of the referrals to the neurosurgical centre, 17% (n = 195) were accepted for transfer and 83% (n = 946) were not accepted. The scoring system was 99% sensitive and 51.9% specific for determining a surgically significant TBI. Diagnostic power of the model was fair with an area under the curve of 0.79 (95% CI 0.76 to 0.82). The score identified 495 (52.2%) patients in ten months of referrals that could have been successfully managed locally without neurosurgical referral if the scoring system was correctly used at the time of injury.Conclusions: The Liverpool Head Injury Tomography Score (HITS) score is a CT-based scoring system that can be used to define a surgically significant mild TBI. The scoring system has high sensitivity and could be incorporated into local, regional and national head injury guidance.


Assuntos
Concussão Encefálica/diagnóstico , Traumatismos Craniocerebrais/diagnóstico por imagem , Encaminhamento e Consulta/estatística & dados numéricos , Medição de Risco/métodos , Concussão Encefálica/etiologia , Concussão Encefálica/terapia , Lesões Encefálicas/etiologia , Traumatismos Craniocerebrais/cirurgia , Traumatismos Craniocerebrais/terapia , Inglaterra , Escala de Coma de Glasgow , Humanos , Neurocirurgia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
17.
Ann Emerg Med ; 75(3): 354-364, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31959538

RESUMO

STUDY OBJECTIVE: We determine the prevalence of significant intracranial injury among adults with blunt head trauma who are receiving preinjury anticoagulant or antiplatelet medications. METHODS: This was a multicenter, prospective, observational study conducted from December 2007 to December 2015. Patients were enrolled in 3 emergency departments (EDs) in the United States. Adults with blunt head trauma who underwent neuroimaging in the ED were included. Use of preinjury aspirin, clopidogrel, and warfarin was recorded. Data on direct oral anticoagulants were not specifically recorded. The primary outcome was prevalence of significant intracranial injury on neuroimaging. The secondary outcome was receipt of neurosurgical intervention. RESULTS: Among 9,070 patients enrolled in this study, the median age was 53.8 years (interquartile range 34.7 to 74.3 years) and 60.7% were men. A total of 1,323 patients (14.6%) were receiving antiplatelet medications or warfarin, including 635 receiving aspirin alone, 109 clopidogrel alone, and 406 warfarin alone. Compared with that of patients without any coagulopathy, the relative risk of significant intracranial injury was 1.29 (95% confidence interval [CI] 0.88 to 1.87) for patients receiving aspirin alone, 0.75 (95% CI 0.24 to 2.30) for those receiving clopidogrel alone, and 1.88 (95% CI 1.28 to 2.75) for those receiving warfarin alone. The relative risk of significant intracranial injury was 2.88 (95% CI 1.53 to 5.42) for patients receiving aspirin and clopidogrel in combination. CONCLUSION: Patients receiving preinjury warfarin or a combination of aspirin and clopidogrel were at increased risk for significant intracranial injury, but not those receiving aspirin alone. Clinicians should have a low threshold for neuroimaging when evaluating patients receiving warfarin or a combination of aspirin and clopidogrel.


Assuntos
Anticoagulantes/efeitos adversos , Lesões Encefálicas/epidemiologia , Traumatismos Cranianos Fechados/complicações , Inibidores da Agregação de Plaquetas/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Lesões Encefálicas/etiologia , Clopidogrel/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores de Risco , Varfarina/efeitos adversos
18.
J Trauma Acute Care Surg ; 88(2): 310-313, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31389914

RESUMO

BACKGROUND: There are no reports comparing wounding pattern in urban and public mass shooting events (CPMS). Because CPMS receive greater media coverage, there is a connation that the nature of wounding is more grave than daily urban gun violence. We hypothesize that the mechanism of death following urban gunshot wounds (GSWs) is the same as has been reported following CPMS. METHODS: Autopsy reports of all firearm-related deaths in Washington, DC were reviewed from January 1, 2016, to December 31, 2017. Demographic data, firearm type, number and anatomic location of GSWs, and organ(s) injured were abstracted. The organ injury resulting in death was noted. The results were compared with a previously published study of 19 CPMS events involving 213 victims. RESULTS: One hundred eighty-six urban autopsy reports were reviewed. There were 171 (92%) homicides and 13 (7%) suicides. Handguns were implicated in 180 (97%) events. One hundred eight (59%) gunshots were to the chest/upper back, 85 (46%) to the head, 77 (42%) to an extremity, and 71 (38%) to the abdomen/lower back. The leading mechanisms of death in both urban firearm violence and CPMS were injury to the brain, lung parenchyma, and heart. Fatal brain injury was more common in CPMS events as compared with urban events involving a handgun. CONCLUSION: There is little difference in wounding pattern between urban and CPMS firearm events. Based on the organs injured, rapid point of wounding care and transport to a trauma center remain the best options for mitigating death following all GSW events. LEVEL OF EVIDENCE: Epidemiological, level IV.


Assuntos
Lesões Encefálicas/mortalidade , Traumatismos Cardíacos/mortalidade , Lesão Pulmonar/mortalidade , Incidentes com Feridos em Massa/estatística & dados numéricos , Ferimentos por Arma de Fogo/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Lesões Encefálicas/etiologia , Lesões Encefálicas/terapia , Causas de Morte , District of Columbia/epidemiologia , Feminino , Traumatismos Cardíacos/etiologia , Traumatismos Cardíacos/terapia , Humanos , Lesão Pulmonar/etiologia , Lesão Pulmonar/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Transporte de Pacientes/estatística & dados numéricos , Centros de Traumatologia/estatística & dados numéricos , Ferimentos por Arma de Fogo/etiologia , Ferimentos por Arma de Fogo/terapia , Adulto Jovem
19.
Acta Neurochir Suppl ; 127: 59-64, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31407064

RESUMO

BACKGROUND: It is reported that the expression of aquaporin4 (AQP4) in the brain is increased and leads to the brain edema after subarachnoid hemorrhage (SAH). In this study, by using AQP4 knockout rat model, the opposite role of AQP4 in early brain injury following SAH through modulation of interstitial fluid (ISF) transportation in the brain glymphatic system had been explored. METHODS: The SAH model was established using endovascular perforation method, the AQP4 knockout rat model was generated using TALENs (transcription activator-like (TAL) effector nucleases) technique. The animals were randomly divided into four groups: sham (n = 16), AQP4-/-sham (n = 16), SAH (n = 24), and AQP4-/-SAH groups (n = 27). The roles of AQP4 in the brain water content and neurological function were detected. In addition, immunohistochemistry and Nissl staining were applied to observe the effects of AQP4 on the blood-brain barrier (BBB) integrity and the loss of neurons in the hippocampus. To explore the potential mechanism of these effects, the distribution of Gd-DTPA (interstitial fluid indicator) injected from cisterna magna was evaluated with MRI. RESULTS: Following SAH, AQP4 knockout could significantly increase the water content in the whole brain and aggravate the neurological deficits. Furthermore, the loss of neuron and BBB disruption in hippocampus were also exacerbated. The MRI results indicated that the ISF transportation in the glymphatic system of AQP4 deficit rat was significantly injured. CONCLUSION: AQP4 facilitates the ISF transportation in the brain to eliminate the toxic factors; AQP4 knockout will aggravate the early brain injury following SAH through impairment of the glymphatic system.


Assuntos
Aquaporina 4 , Edema Encefálico , Lesões Encefálicas , Hemorragia Subaracnóidea , Animais , Aquaporina 4/fisiologia , Encéfalo , Lesões Encefálicas/etiologia , Técnicas de Inativação de Genes , Sistema Glinfático , Ratos , Hemorragia Subaracnóidea/genética , Hemorragia Subaracnóidea/patologia
20.
Forensic Sci Int ; 307: 110118, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31869653

RESUMO

Brain and cervical injuries are often described after major facial impacts but rarely after low-intensity mandibular impacts. Force transmission to the brain and spinal cord from a mandibular impact such as a punch was evaluated by the creation and validation of a complete finite element model of the head and neck. Anteroposterior uppercut impacts on the jaw were associated with considerable extension and strong stresses at the junction of the brainstem and spinal cord. Hook punch impacts transmitted forces directly to the brainstem and the spinal cord without extension of the spinal cord. Deaths after this type of blow with no observed histological lesions may be related to excessive stressing of the brainstem, through which pass the sensory-motor pathways and the vagus nerve and which is the regulatory center of the major vegetative functions. Biological parameters are different in each individual, and by using digital modeling they can be modulated at will (jaw shape, dentition…) for a realistic approach to forensic applications.


Assuntos
Lesões Encefálicas/diagnóstico por imagem , Simulação por Computador , Traumatismos Mandibulares/diagnóstico por imagem , Traumatismos da Medula Espinal/diagnóstico por imagem , Adulto , Lesões Encefálicas/etiologia , Análise de Elementos Finitos , Medicina Legal/métodos , Humanos , Imageamento Tridimensional , Masculino , Traumatismos Mandibulares/complicações , Abuso Físico , Traumatismos da Medula Espinal/etiologia , Tomografia Computadorizada por Raios X
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