Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.665
Filtrar
1.
Isr Med Assoc J ; 22(1): 27-31, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31927802

RESUMO

BACKGROUND: Congenital heart defects (CHD) may be associated with neurodevelopmental abnormalities mainly due to brain hypoperfusion. This defect is attributed to the major cardiac operations these children underwent, but also to hemodynamic instability during fetal life. Advances in imaging techniques have identified changes in brain magnetic resonance imaging (MRI)in children with CHD. OBJECTIVES: To examine the correlation between CHD and brain injury using fetal brain MRI. METHODS: We evaluated 46 fetuses diagnosed with CHD who underwent brain MRI. CHD was classified according to in situs anomalies, 4 chamber view (4CV), outflow tracts, arches, and veins as well as cyanotic or complex CHD. We compared MRI results of different classes of CHD and CHD fetuses to a control group of 113 healthy brain MRI examinations. RESULTS: No significant differences were found in brain pathologies among different classifications of CHD. The anteroposterior percentile of the vermis was significantly smaller in fetuses with abnormal 4CV. A significantly higher biparietal diameter was found in fetuses with abnormal arches. A significantly smaller transcerebellar diameter was found in fetuses with abnormal veins. Compared to the control group, significant differences were found in overall brain pathology in cortex abnormalities and in extra axial findings in the study group. Significantly higher rates of overall brain pathologies, ventricle pathologies, cortex pathologies, and biometrical parameters were found in the cyanotic group compared to the complex group and to the control group. CONCLUSIONS: Fetuses with CHD demonstrate findings in brain MRI that suggest an in utero pathogenesis of the neurological and cognitive anomalies found during child development.


Assuntos
Lesões Encefálicas/embriologia , Feto/diagnóstico por imagem , Cardiopatias Congênitas/etiologia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/embriologia , Encéfalo/patologia , Lesões Encefálicas/complicações , Lesões Encefálicas/diagnóstico por imagem , Lesões Encefálicas/patologia , Estudos de Casos e Controles , Ecocardiografia , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Neuroimagem , Gravidez , Diagnóstico Pré-Natal/métodos
2.
Adv Exp Med Biol ; 1232: 63-68, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893395

RESUMO

This seems to be the time to gain new knowledge about the meningeal lymphatic system and a deeper understanding of its anatomy and physiology. Although it is known that the meningeal lymphatics present in the layers of the brain, limited information is available about the role of this system in brain function. Here, for the first time we clearly demonstrate that the meningeal lymphatic pathway is involved in brain clearing from the blood after intracranial hemorrhage associated with hypoxia and forms a connective bridge between interstitial, cerebral spinal fluid and peripheral lymphatics. We also show that the development of methods to stimulate meningeal lymph flow after hemorrhagic evidence in the brain might be a neuroprotective strategy for effective recovery of the brain after a cerebrovascular catastrophe.


Assuntos
Hemorragias Intracranianas , Vasos Linfáticos , Meninges , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Hemorragias Intracranianas/metabolismo , Hemorragias Intracranianas/patologia , Sistema Linfático , Vasos Linfáticos/fisiologia , Meninges/metabolismo , Meninges/patologia
3.
Biochemistry (Mosc) ; 84(11): 1306-1328, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31760920

RESUMO

Focal brain injuries (in particular, stroke and traumatic brain injury) induce with high probability the development of delayed (months, years) cognitive and depressive disturbances which are frequently comorbid. The association of these complications with hippocampal alterations (in spite of the lack of a primary injury of this structure), as well as the lack of a clear dependence between the probability of depression and dementia development and primary damage severity and localization served as the basis for a new hypothesis on the distant hippocampal damage as a key link in the pathogenesis of cognitive and psychiatric disturbances. According to this hypothesis, the excess of corticosteroids secreted after a focal brain damage, in particular in patients with abnormal stress-response due to hypothalamic-pituitary-adrenal axis (HPAA) dysfunction, interacts with corticosteroid receptors in the hippocampus inducing signaling pathways which stimulate neuroinflammation and subsequent events including disturbances in neurogenesis and hippocampal neurodegeneration. In this article, the molecular and cellular mechanisms associated with the regulatory role of the HPAA and multiple functions of brain corticosteroid receptors in the hippocampus are analyzed. Functional and structural damage to the hippocampus, a brain region selectively vulnerable to external factors and responding to them by increased cytokine secretion, forms the basis for cognitive function disturbances and psychopathology development. This concept is confirmed by our own experimental data, results of other groups and by prospective clinical studies of post-stroke complications. Clinically relevant biochemical approaches to predict the risks and probability of post-stroke/post-trauma cognitive and depressive disturbances are suggested using the evaluation of biochemical markers of patients' individual stress-response. Pathogenetically justified ways for preventing these consequences of focal brain damage are proposed by targeting key molecular mechanisms underlying hippocampal dysfunction.


Assuntos
Lesões Encefálicas/patologia , Hipocampo/metabolismo , Animais , Lesões Encefálicas/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Citocinas/metabolismo , Humanos , Estresse Oxidativo , Sistema Hipófise-Suprarrenal , Receptores de Esteroides/metabolismo
4.
Life Sci ; 235: 116821, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31476306

RESUMO

AIMS: This study aims to examine the effects of electroacupuncture (EA) pretreatment on brain injury after cardiac arrest and cardiopulmonary resuscitation (CA/CPR) and its underlying mechanisms. MATERIALS AND METHODS: Adult male C57BL/6 mice were subjected to 6 min of cardiac arrest induced with a potassium chloride infusion and resuscitated by chest compressions and an epinephrine infusion. During the 3 days prior to CA/CRP, mice received EA pretreatment (1 mA, 2 Hz; daily session of 30 min) at the Baihui acupoint (GV20) once daily. Stimulation at a nonacupoint served as a control. In mechanistic studies, mice received the AKT inhibitor LY294002 or endothelial nitric oxide synthase (eNOS) inhibitor L-NIO 30 min before EA pretreatment. A neurological assessment was conducted 24 h after CA/CRP, followed by animal sacrifice and evaluation of physiological brain damage. KEY FINDINGS: CA/CPR resulted in severe brain injury as evidenced by neurological deficits and increased neuronal apoptosis, oxidative stress and the proinflammatory cytokines TNF-α and IL-6. EA pretreatment at the GV20 acupoint but not at a nonacupoint attenuated the neurological deficits and the pathological changes induced by CA/CPR. LY294002 or L-NIO eliminated the neuroprotective effects of the EA pretreatment. SIGNIFICANCE: This study showed that EA pretreatment at the GV20 acupoint can protect the brain from damage associated with globalized ischemia followed by reperfusion and that these protective effects occur via the AKT/eNOS signaling pathway.


Assuntos
Lesões Encefálicas/terapia , Reanimação Cardiopulmonar/efeitos adversos , Modelos Animais de Doenças , Eletroacupuntura/métodos , Parada Cardíaca/complicações , Fármacos Neuroprotetores , Óxido Nítrico Sintase Tipo III/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Lesões Encefálicas/etiologia , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo III/genética , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-akt/genética
5.
J Biol Regul Homeost Agents ; 33(4): 1051-1062, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31392878

RESUMO

The development of electronic technology has attracted attention on the biological effects of electromagnetic fields (EMFs) and electromagnetic pulse (EMP). It remains controversial whether EMP irradiation is neurotoxic or beneficial for recovery from injuryies such as cerebral ischemia. Microglia is innate immune cells in the brain, exhibiting either neurotoxicity or neuroprotection effect during various central nervous system diseases, depending on their activation into a classical (M1) or alternative (M2) phenotype, respectively. The Toll-like receptor-4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor kappa B (NFκB) pathway is important for microglia activation. In this study, we investigated the effect of EMP on neuronal apoptosis and microglia polarization in vivo and in vitro, using an EMP of 400 kV/m and 1 hertz for 200 pulses. Short EMP irradiation (≤24 h) resulted in microglial conversion from the resting to the M1-type state, activation of the TLR4/MyD88/NFκB pathway, higher levels of inflammatory cytokines including interleukin (IL)-6, IL-1ß and tumor necrosis factor-α, as well as neuronal apoptosis induction. In contrast, long EMP irradiation (3 days) resulted in microglial activation into the M2-type, decreased apoptosis and inflammatory mediator production, and increased levels of the neuroprotective effectors IL-10, transforming growth factor beta, and brain-derived neurotrophic factor. EMP induces both neuronal damage and neuronal recovery by influencing the switch of M1/M2 polarization and the TLR4/MyD88/NFκB pathway.


Assuntos
Lesões Encefálicas/patologia , Polaridade Celular , Campos Eletromagnéticos/efeitos adversos , Microglia/citologia , Citocinas/metabolismo , Humanos , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo
6.
Int J Mol Med ; 44(3): 813-822, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31257456

RESUMO

The key to successful treatment of cerebral venous­sinus occlusion (CVO) is the rapid recanalization of the sinus following venous­sinus occlusion; however, rapid recanalization of the sinus may also cause secondary cerebral injury. The present study examined mechanical thrombectomy­related brain injury and the possible molecular mechanisms following CVO recanalization, and investigated the protective effect of glycyrrhizin (GL) in CVO recanalization. The cerebral venous sinus thrombosis (CVST) model was induced in rats using 40% FeCl3. Mechanical thrombectomy was performed at 6 h post­thrombosis. GL was administered to rats following thromboembolism. Neurological function and brain water content were measured prior to sacrifice of the rats. Serum malondialdehyde, superoxide dismutase and nitric­oxide synthase concentrations were measured. The expression levels of high­mobility group box 1 (HMGB1) and receptor of advanced glycation end products (RAGE) and its downstream inflammatory mediators were measured in serum and brain tissues. Rapid CVO recanalization caused brain injury, and the brain parenchymal damage and neurological deficits caused by CVO were not completely restored following recanalization. Similarly, following rapid recanalization in the venous sinus, the expression levels of HMGB1 and RAGE were lower than those in the CVST group, but remained significantly higher than those of the sham group. The combination of mechanical thrombectomy and GL improved cerebral infarction and cerebral edema in rats, and inhibited the extracellular transport of HMGB1, and the expression of downstream inflammatory factors and oxidative­stress products. The administration of exogenous recombinant HMGB1 reversed the neural protective effects of GL. In conclusion, mechanical thrombectomy subsequent to CVO in rats can cause brain injury following recanalization. HMGB1 and RAGE promote inflammation in the process of brain injury following recanalization. GL has a relatively reliable neuroprotective effect on brain injury by inhibiting HMGB1 and its downstream inflammatory factors, and decreasing oxidative stress.


Assuntos
Lesões Encefálicas/etiologia , Ácido Glicirrízico/farmacologia , Proteína HMGB1/genética , Fármacos Neuroprotetores/farmacologia , Receptor para Produtos Finais de Glicação Avançada/genética , Trombectomia , Animais , Biomarcadores , Biópsia , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Lesões Encefálicas/terapia , Expressão Gênica , Proteína HMGB1/metabolismo , Masculino , Ratos , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Trombose dos Seios Intracranianos/complicações , Trombose dos Seios Intracranianos/terapia , Trombectomia/métodos
7.
Mol Med Rep ; 20(2): 1837-1845, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31257533

RESUMO

Hypoxic preconditioning (HPC) is neuroprotective against ischaemic brain injury; however, the roles of potential anti­apoptotic signals in this process have not been assessed. To elucidate the molecular mechanisms involved in HPC­induced neuroprotection, the effects of HPC on the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP response element­binding protein (CREB) signalling pathway and apoptosis in Sprague­Dawley pups (postnatal day 7) treated with propofol were investigated. Western blot and histological analyses demonstrated that HPC exerts multiple effects on the hippocampus, including the upregulation of cAMP and phosphorylation of CREB. These effects were partially blocked by intracerebroventricular injection of the protein kinase antagonist H89 (5 µmol/5 µl). Notably, the level of cleaved caspase­3 was significantly downregulated by treatment with the cAMP agonist Sp­cAMP (20 nmol/5 µl). The results indicate that propofol increased the level of cleaved caspase­3 and Bax by suppressing the activity of cAMP­dependent proteins and Bcl­2; thus, HPC prevents propofol from triggering apoptosis via the cAMP/PKA/CREB signalling pathway.


Assuntos
Lesões Encefálicas/terapia , Precondicionamento Isquêmico/métodos , Neurônios/metabolismo , Neuroproteção/genética , Animais , Animais Recém-Nascidos , Apoptose/genética , Lesões Encefálicas/genética , Lesões Encefálicas/patologia , Lesões Encefálicas/prevenção & controle , AMP Cíclico , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteínas Quinases Dependentes de AMP Cíclico/genética , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Neurônios/patologia , Fosforilação/genética , Propofol/toxicidade , Ratos , Transdução de Sinais/genética , Lobo Temporal/metabolismo , Lobo Temporal/patologia
8.
Crit Care ; 23(1): 198, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159847

RESUMO

BACKGROUND: In recent years, argon has been shown to exert neuroprotective effects in an array of models. However, the mechanisms by which argon exerts its neuroprotective characteristics remain unclear. Accumulating evidence imply that argon may exert neuroprotective effects via modulating the activation and polarization of microglia/macrophages after ischemic stroke. In the present study, we analyzed the underlying neuroprotective effects of delayed argon application until 7 days after reperfusion and explored the potential mechanisms. METHODS: Twenty-one male Wistar rats underwent transient middle cerebral artery occlusion or sham surgery randomly for 2 h using the endoluminal thread model. Three hours after transient middle cerebral artery occlusion induction and 1 h after reperfusion, animals received either 50% vol Argon/50% vol O2 or 50% vol N2/50% vol O2 for 1 h. The primary outcome was the 6-point neuroscore from 24 h to d7 after reperfusion. Histological analyses including infarct volume, survival of neurons (NeuN) at the ischemic boundary zone, white matter integrity (Luxol Fast Blue), microglia/macrophage activation (Iba1), and polarization (Iba1/Arginase1 double staining) on d7 were conducted as well. Sample size calculation was performed using nQuery Advisor + nTerim 4.0. Independent t test, one-way ANOVA and repeated measures ANOVA were performed, respectively, for statistical analysis (SPSS 23.0). RESULTS: The 6-point neuroscore from 24 h to d7 after reperfusion showed that tMCAO Ar group displayed significantly improved neurological performance compared to tMCAO N2 group (p = 0.026). The relative numbers of NeuN-positive cells in the ROIs of tMCAO Ar group significantly increased compared to tMCAO N2 group (p = 0.010 for cortex and p = 0.011 for subcortex). Argon significantly suppressed the microglia/macrophage activation as revealed by Iba1 staining (p = 0.0076) and promoted the M2 microglia/macrophage polarization as revealed by Iba1/Arginase 1 double staining (p = 0.000095). CONCLUSIONS: Argon administration with a 3 h delay after stroke onset and 1 h after reperfusion significantly alleviated neurological deficit within the first week and preserved the neurons at the ischemic boundary zone 7 days after stroke. Moreover, argon reduced the excessive microglia/macrophage activation and promoted the switch of microglia/macrophage polarization towards the anti-inflammatory M2 phenotype. Studies making efforts to further elucidate the protective mechanisms and to benefit the translational application are of great value.


Assuntos
Argônio/farmacologia , Lesões Encefálicas/fisiopatologia , Encefalite/prevenção & controle , Acidente Vascular Cerebral/tratamento farmacológico , Análise de Variância , Animais , Argônio/uso terapêutico , Lesões Encefálicas/etiologia , Lesões Encefálicas/patologia , Modelos Animais de Doenças , Encefalite/fisiopatologia , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/fisiopatologia , Masculino , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Distribuição Aleatória , Ratos , Ratos Wistar/lesões , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/fisiopatologia
9.
Molecules ; 24(11)2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31174251

RESUMO

Ginseng has been used to alleviate age-related dementia and memory deterioration for thousands of years. This study investigated the protective effect of red ginseng saponins against scopolamine-induced cerebral injury. Meanwhile, pharmacokinetics of ginsenosides in normal and scopolamine-treated rats were compared. After scopolamine injection, glutathione, catalase and superoxide dismutase levels were significantly decreased when compared with control group. Compared with SA group, pretreatment of rats with red ginseng saponins could increase glutathione, catalase and superoxide dismutase level. Treatment with red ginseng saponins significantly decreased malondialdehyde level. In the pharmacokinetic analysis, a pattern recognition analysis method was used to investigate the pharmacokinetics of the absorbed compounds in blood. The pharmacokinetic parameters of Rg1, Rg2, Rh3, Rg5 and Rk1 in model group had higher area under the curve (AUC), mean residence time (MRT) and peak plasma concentration (Cmax) values; area under the curve (AUC) values and peak plasma concentration (Cmax) of model group was significantly different from that of normal group (p < 0.05). The Cmax value of Rk3, Rh1, Rh2 and Rh4 in model group was higher than normal group, but their AUC values were not significantly different. There was no significantly difference in time at Cmax (Tmax), AUC and Cmax values of Rb1, Rb2 Re, Rc, Rd and Rf between the model and normal group. 16 ginsenosides were grouped into three separate clusters according to principal component analysis (PCA) score plot based on pharmacokinetic data. The results suggested red ginseng saponins have significant protective effect against scopolamine-induced memory deficit and scopolamine-induced rats could lead to the changes of pharmacokinetic behaviors of ginsenosides.


Assuntos
Lesões Encefálicas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Panax/química , Saponinas/farmacologia , Animais , Lesões Encefálicas/induzido quimicamente , Lesões Encefálicas/patologia , Humanos , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/patologia , Fármacos Neuroprotetores/farmacocinética , Ratos , Ratos Sprague-Dawley , Saponinas/química , Saponinas/farmacocinética , Escopolamina/toxicidade
10.
Eur J Paediatr Neurol ; 23(4): 604-608, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31147107

RESUMO

Pediatric abusive head trauma (AHT) or non accidental head trauma (NAHT) is a major cause of death from trauma in children under 2 years of age. Main etiological factor for non accidental head trauma is shaking a baby, causing brain injury by rotational head acceleration and deceleration. The consequent brain damage as shown by magnetic resonance imaging (MRI) is subdural haemorrhage and to a lesser extent parenchymal injuries of variable severity. Involvement of the cerebellum has very rarely been described. We report the clinical history and the development of cerebral magnetic resonance imaging findings in two children with serious brain injury following probable shaking who presented the typical "triad" with subdural haematoma, retinal haemorrhage and encephalopathy. We want to draw attention to cerebellar involvement characterized by cortico-subcortical signal alterations most prominent on T2w images following diffusion changes during the acute period. We discuss cerebellar involvement as a sign of higher severity of AHT which is probably underrecognized.


Assuntos
Lesões Encefálicas/patologia , Cerebelo/lesões , Cerebelo/patologia , Maus-Tratos Infantis , Traumatismos Craniocerebrais/patologia , Lesões Encefálicas/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Maus-Tratos Infantis/diagnóstico , Traumatismos Craniocerebrais/diagnóstico por imagem , Feminino , Humanos , Lactente , Imagem por Ressonância Magnética/métodos , Masculino
11.
Crit Care ; 23(1): 234, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253189

RESUMO

BACKGROUND: Brain injury (BI) induces a state of immunodepression leading to pneumonia. We investigated the invariant natural killer T (iNKT) cell compartment. METHODS: This is an observational study in two surgical intensive care units (ICUs) of a single institution and a research laboratory. Clinical data and samples from a prospective cohort were extracted. Severe brain-injured patients (n = 33) and sex- and age-matched healthy donors (n = 40) were studied. RESULTS: We observed the presence of IL-10 in serum, a loss of IFN-γ and IL-13 production by peripheral blood mononuclear cells (PBMCs) following IL-2 stimulation, and downregulation of HLA-DR expression on both monocytes and B cells early after BI. Inversely, CD1d, the HLA class I-like molecule involved in antigen presentation to iNKT cells, was over-expressed on patients' monocytes and B cells. The antigen-presenting activity to iNKT cells of PBMCs was increased in the patients who developed pneumonia, but not in those who remained free of infection. Frequencies of iNKT cells among PBMCs were dramatically decreased in patients regardless of their infection status. Following amplification, an increased frequency of CD4+ iNKT cells producing IL-4 was noticed in the group of patients free of infection compared with those who became infected and with healthy donors. Finally, serum from BI patients inhibited the iNKT cells' specific response as well as the non-specific IL-2 stimulation of PBMCs, and the expression of the beta-2 adrenergic receptor was elevated at the surface of patients T lymphocytes. CONCLUSIONS: We observed severe alterations of the iNKT cell compartment, including the presence of inhibitory serum factors. We demonstrate for the first time that the decreased capacity to present antigens is not a generalized phenomenon because whereas the expression of HLA-DR molecules is decreased, the capacity for presenting glycolipids through CD1d expression is higher in patients.


Assuntos
Lesões Encefálicas/fisiopatologia , Compartimento Celular/fisiologia , Células T Matadoras Naturais/ultraestrutura , Lesões Encefálicas/patologia , Cardiotônicos/uso terapêutico , Hidratação/métodos , Hidratação/tendências , Humanos
12.
J Rehabil Med ; 51(7): 499-505, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31165172

RESUMO

BACKGROUND: Brain injury causes multiple symptoms. Among these, visual disturbances are common; 50-70% of patients experience some change in vision after injury/illness. Other very common and disabling symptoms are fatigue, anxiety and depression. This study examines whether levels of fatigue, anxiety and depression are increased if the patients also experience vision disorders. MATERIALS AND METHODS: A total of 123 patients enrolled in day care rehabilitation unit for medium-to-severe brain injury completed questionnaires about self-experienced fatigue, anxiety, depression and self-experienced level and type of visual disturbances. Symptoms of fatigue, anxiety and depression were compared with the occurrence of visual disturbances. Analyses were performed using binary logistic regression. RESULTS: An association was found between visual symptoms and fatigue, but not between visual symptoms and anxiety/depression. However, some visual symptoms, such as glare, blurred vision and reading difficulties, showed great differences between patients with or without anxiety/depression. CONCLUSION: Vision rehabilitation may be a tool for mitigating fatigue after acquired brain injury.


Assuntos
Ansiedade/etiologia , Lesões Encefálicas/complicações , Depressão/etiologia , Fadiga Mental/etiologia , Transtornos da Visão/etiologia , Adulto , Lesões Encefálicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
13.
Cell Mol Life Sci ; 76(20): 3953-3967, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31250034

RESUMO

The brain tissue has only a limited capacity for generating new neurons. Therefore, to treat neurological diseases, there is a need of other cell sources for brain repair. Different sources of cells have been subject of intense research over the years, including cells from primary tissue, stem cell-derived cells and reprogrammed cells. As an alternative, direct reprogramming of resident brain cells into neurons is a recent approach that could provide an attractive method for treating brain injuries or diseases as it uses the patient's own cells for generating novel neurons inside the brain. In vivo reprogramming is still in its early stages but holds great promise as an option for cell therapy. To date, both inhibitory and excitatory neurons have been obtained via in vivo reprogramming, but the precise phenotype or functionality of these cells has not been analysed in detail in most of the studies. Recent data shows that in vivo reprogrammed neurons are able to functionally mature and integrate into the existing brain circuitry, and compose interneuron phenotypes that seem to correlate to their endogenous counterparts. Interneurons are of particular importance as they are essential in physiological brain function and when disturbed lead to several neurological disorders. In this review, we describe a comprehensive overview of the existing studies involving brain repair, including in vivo reprogramming, with a focus on interneurons, along with an overview on current efforts to generate interneurons for cell therapy for a number of neurological diseases.


Assuntos
Lesões Encefálicas/terapia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Células-Tronco Pluripotentes Induzidas/citologia , Interneurônios/citologia , Doenças Neurodegenerativas/terapia , Regeneração/fisiologia , Animais , Biomarcadores/metabolismo , Encéfalo/citologia , Encéfalo/metabolismo , Lesões Encefálicas/genética , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Transdiferenciação Celular , Reprogramação Celular , Fibroblastos/citologia , Fibroblastos/metabolismo , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Injeções Intraventriculares , Interneurônios/metabolismo , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Neurogênese/genética , Transplante de Células-Tronco/métodos
14.
Med Biol Eng Comput ; 57(9): 1917-1931, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31250276

RESUMO

Electrical impedance tomography (EIT) is a non-invasive and real-time imaging method that has the potential to be used for monitoring intracerebral hemorrhage (ICH). Recent studies have proposed that ischemia secondary to ICH occurs simultaneously in the brain. Real-time monitoring of the development of hemorrhage and risk of secondary ischemia is crucial for clinical intervention. However, few studies have explored the performance of EIT monitoring in cases where hemorrhage and secondary ischemia exist. When these lesions get close to each other, or their conductivity and volume changes differ greatly, it becomes challenging for dynamic EIT algorithms to simultaneously reconstruct subtle injuries. To address this, an iterative damped least-squares (IDLS) algorithm is proposed in this study. The quality of the IDLS algorithm was assessed using blur radius and temporal response during computer simulation and a phantom 3D head-shaped model where bidirectional disturbance targets were simulated. The results showed that the IDLS algorithm enhanced contrast and concurrently reconstructed bidirectional disturbance targets in images. Moreover, it showed superior performance in decreasing the blur radius and was time cost-effective. With further improvement, the IDLS algorithm has the potential to be used for monitoring the development of hemorrhage and risk of ischemia secondary to ICH. Graphical abstract (a) and (b) are simulation images of bidirectional disturbance targets with different change ratios of volume (Vr) and conductivity (σr) based on the damped least-squares (DLS) algorithm and iterative damped least-squared (IDLS) algorithm, respectively. (c) shows the performance metrics of blur radius and temporal response with different volume ratio (corresponding to Vr). (d) shows the performance metrics of blur radius and temporal response with different conductivity change percentage (corresponding to σr).


Assuntos
Algoritmos , Lesões Encefálicas/patologia , Isquemia Encefálica/patologia , Hemorragias Intracranianas/patologia , Monitorização Fisiológica/métodos , Lesões Encefálicas/complicações , Simulação por Computador , Impedância Elétrica , Humanos , Processamento de Imagem Assistida por Computador/métodos , Análise dos Mínimos Quadrados , Imagens de Fantasmas , Tomografia Computadorizada por Raios X
15.
EBioMedicine ; 45: 615-623, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31208948

RESUMO

Intracranial haemorrhage (ICH) is a life-threatening type of stroke with high mortality, morbidity, and recurrence rates. However, no effective treatment has been established to improve functional outcomes in patients with ICH to date. Strategies targeting secondary brain injury are of great interest in both experimental and translational studies. The immune system is increasingly considered to be a crucial contributor to ICH-induced brain injury because it participates in multiple phases of ICH, from the early vascular rupture events to brain recovery. Various pathobiological processes that contribute to secondary brain injury closely interact with the immune system, such as brain oedema, neuroinflammation, and neuronal damage. Hence, we summarize the immune response to ICH and recent progress in treatments targeting the immune system in this review. The emerging therapeutic strategies that target the immune system after ICH are a particular focus and have been summarized.


Assuntos
Edema Encefálico/imunologia , Lesões Encefálicas/imunologia , Hemorragia Cerebral/imunologia , Inflamação/imunologia , Animais , Encéfalo/imunologia , Encéfalo/patologia , Edema Encefálico/patologia , Edema Encefálico/terapia , Lesões Encefálicas/patologia , Lesões Encefálicas/terapia , Hemorragia Cerebral/patologia , Hemorragia Cerebral/terapia , Humanos , Sistema Imunitário/patologia , Inflamação/patologia , Inflamação/terapia , Neurônios/imunologia , Neurônios/patologia , Pesquisa Médica Translacional
16.
Int J Med Sci ; 16(5): 675-685, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31217735

RESUMO

Background: Exercise preconditioning (EP+) is a useful and important procedure for the prevention of stroke. We aimed to ascertain whether EP+ protects against ischemic brain injury by preserving heat shock protein (HSP) 72-containing neurons in ischemic brain tissues. Methods: Adult male Sprague-Dawley rats (n=240) were used to assess the contribution of HSP72-containing neurons to the neuroprotective effects of EP+ on ischemic brain injury caused by transient middle cerebral artery occlusion. Results: Significant (P<0.05) increases in the percentages of both old HSP72-containing neurons (NeuN+HSP72 double positive cells) (18~20% vs. 40~50%) and newly formed HSP72-containing neurons (BrdU+NeuN+HSP72 triple positive cells); (2~3% vs. 16~20%) after 3 weeks of exercise coincided with significant (P<0.05) reductions in brain ischemia volume (250 mm3 vs. 100 mm3), brain edema (78% vs. 74% brain water content), blood-brain barrier disruption (1.5 µg/g vs. 0.7 µg/g tissue Evans Blue dye extravasation) and neurological motor deficits (neurological severity scores of 12 vs. 6 and maximal angles of 60° vs. 20°) in brain ischemia rats. Reductions in the percentages of both old (from 40~50% to 10~12%) and newly formed (from 18~20% to 5~7%) HSP72-containing neurons by gene silencing with an intracerebral injection of pSUPER small interfering RNA showed a significant (P<0.05) reversal in the neuroprotective outcomes. Our data provide an inverse correlation between the EP+-mediated increases in both old and newly formed HSP72-containing neurons and the extent of cerebral ischemic injury. Conclusions: The percentages of both old and newly formed HSP72-containing neurons are inversely correlated with the outcomes of ischemic brain injury. Additionally, preischemic treadmill exercise improves the outcomes of ischemic brain injury by preserving both the old and newly formed HSP72-containing neurons in rats.


Assuntos
Lesões Encefálicas/terapia , Isquemia Encefálica/terapia , Proteínas de Choque Térmico HSP72/genética , Condicionamento Físico Animal , Animais , Encéfalo/fisiopatologia , Lesões Encefálicas/etiologia , Lesões Encefálicas/genética , Lesões Encefálicas/patologia , Isquemia Encefálica/etiologia , Isquemia Encefálica/genética , Isquemia Encefálica/patologia , Humanos , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/patologia , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores , Ratos , Ratos Sprague-Dawley
17.
Nat Med ; 25(5): 784-791, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31061540

RESUMO

Owing to recent medical and technological advances in neonatal care, infants born extremely premature have increased survival rates1,2. After birth, these infants are at high risk of hypoxic episodes because of lung immaturity, hypotension and lack of cerebral-flow regulation, and can develop a severe condition called encephalopathy of prematurity3. Over 80% of infants born before post-conception week 25 have moderate-to-severe long-term neurodevelopmental impairments4. The susceptible cell types in the cerebral cortex and the molecular mechanisms underlying associated gray-matter defects in premature infants remain unknown. Here we used human three-dimensional brain-region-specific organoids to study the effect of oxygen deprivation on corticogenesis. We identified specific defects in intermediate progenitors, a cortical cell type associated with the expansion of the human cerebral cortex, and showed that these are related to the unfolded protein response and changes. Moreover, we verified these findings in human primary cortical tissue and demonstrated that a small-molecule modulator of the unfolded protein response pathway can prevent the reduction in intermediate progenitors following hypoxia. We anticipate that this human cellular platform will be valuable for studying the environmental and genetic factors underlying injury in the developing human brain.


Assuntos
Lesões Encefálicas/etiologia , Hipóxia Encefálica/etiologia , Modelos Neurológicos , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Hipóxia Celular/genética , Hipóxia Celular/fisiologia , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Humanos , Hipóxia Encefálica/metabolismo , Hipóxia Encefálica/patologia , Lactente Extremamente Prematuro , Recém-Nascido , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/patologia , Neurogênese/genética , Neurogênese/fisiologia , Organoides/metabolismo , Organoides/patologia , Proteínas com Domínio T/metabolismo , Resposta a Proteínas não Dobradas
18.
Acta Cir Bras ; 34(4): e201900401, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31066785

RESUMO

PURPOSE: To investigate the relations of neuropeptide Y (NPY) and heme oxygenase-1 (HO-1) expressions with fetal brain injury in rats with intrahepatic cholestasis of pregnancy (ICP). METHODS: Sixty rats pregnant for 15 days were randomly divided into experimental and control groups. The ICP model was established in experimental group. On the 21st day, the blood biochemical test, histopathological examination of pregnant rat liver and fetal brain tissues and immunohistochemical analysis of fetal rat brain tissues were performed. RESULTS: On the 21st day, the alanineaminotransferase, aspartate aminotransferase and total bile acid levels in experimental group were significantly higher than control group (P<0.01). Compared with control group, there was obvious vacuolar degeneration in pregnant rat liver tissue and fetal brain tissue in experimental group. NPY expression in fetal brain tissue was negative in control group and positive in experimental group. HO-1 expression in fetal brain tissue was strongly positive in control group and positive in experimental group. There was significant difference of immunohistochemical staining optical density between two groups (P<0.01). CONCLUSION: In fetal brain of ICP rats, the NPY expression is increased, and the HO-1 expression is decreased, which may be related to the fetal brain injury.


Assuntos
Lesões Encefálicas/metabolismo , Colestase Intra-Hepática/metabolismo , Heme Oxigenase-1/metabolismo , Neuropeptídeo Y/metabolismo , Complicações na Gravidez/metabolismo , Animais , Lesões Encefálicas/etiologia , Lesões Encefálicas/patologia , Colestase Intra-Hepática/complicações , Colestase Intra-Hepática/patologia , Modelos Animais de Doenças , Feminino , Imuno-Histoquímica , Gravidez , Complicações na Gravidez/patologia , Ratos , Ratos Sprague-Dawley
19.
Stroke ; 50(6): 1548-1557, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31084324

RESUMO

Background and Purpose- Ischemia attracts neutrophils to the injured brain. However, neutrophil location and access to the damaged brain tissue is not yet entirely understood. We aimed to investigate neutrophil location in a mouse model of cerebral ischemia/reperfusion. Methods- Adult male C57BL/6 mice (n=52) received 45-minute intraluminal middle cerebral artery occlusion followed by 14, 24, 48, or 96 hours of reperfusion. Sham-operated mice (n=9) were subjected to the entire surgical procedure. We used wild-type mice and CatchupIVM mice expressing a red fluorescent protein in neutrophils. In addition, fluorescent neutrophils obtained from reporter DsRed (discosoma red fluorescent protein) mice were transferred intravenously to wild-type mice after ischemia. Mice received transcardial paraformaldehyde perfusion, the brain was cryoprotected, frozen, and cryostat sections were studied by immunofluorescence and confocal microscopy. Results- Ischemia induced a time-dependent increase in brain neutrophil numbers versus sham operation. We detected neutrophils in the leptomeninges, ventricles, capillary lumen, perivascular spaces, and parenchyma within the infarcted core. Most ischemic mice showed neutrophils in the leptomeninges and perivascular spaces, whereas the presence and number of neutrophils in the parenchyma was variable among ischemic mice. During the first 24 hours, only a few mice showed parenchymal neutrophils, but the frequency of mice showing neutrophils in the parenchyma and neutrophil numbers increased at 48 and 96 hours. We also detected signs of basement membrane disruption and hints of occasional neutrophil degranulation and formation of neutrophil extracellular traps. Conclusions- After ischemia/reperfusion, neutrophils accumulate in the leptomeninges and perivascular spaces, and eventually can reach the infarcted brain parenchyma.


Assuntos
Lesões Encefálicas , Encéfalo , Degranulação Celular , Armadilhas Extracelulares/metabolismo , Neutrófilos , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Masculino , Camundongos , Camundongos Transgênicos , Neutrófilos/metabolismo , Neutrófilos/patologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Fatores de Tempo
20.
J Nepal Health Res Counc ; 17(1): 56-60, 2019 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-31110378

RESUMO

BACKGROUND: Head injury is a common problem encountered in emergency department. Among various neurological diseases, cranio-cerebral trauma ranks high in order of frequency and gravity. In acute setting, computed tomography is modality of choice because of its high accuracy in detecting intracranial lesions. The study was done to analyze computed tomography findings in cerebral trauma in regards to sociodemographic characteristics and find out associations of Computed tomography findings with mechanism of injury and clinical manifestations. METHODS: The study was carried in Department of Radiology, BPKIHS, over a period of one year from Aug. 2015 to Aug. 2016. 450 patients were included in our study and findings noted on structured pro forma. Analysis was done using SPSS version 20 applying simple descriptive statistical methods. RESULTS: Among 450 patients, 220 patients (48.9%) had various cranio-cerebral injuries. Most were in age group of 20-29 years (49.5%) and most common mode was road traffic accident (44.6%).Most patients presented with altered sensorium (39.2%) and Glasgow Coma Scale score of ?13 (70.9%). Scalp lesion was the most common finding (24%) followed by bone fractures (19.8 %). Patients with road traffic accident (59.7%) and fall from height (46.7%) had more positive computed tomography findings than from physical assault (28.2%). Glasgow Coma Scale showed significant statistical association with computed tomography findings (p<0.001). CONCLUSIONS: Road traffic accident is the most common mode of head injury in young adults patients presenting in our hospital. Glasgow Coma Scale can be considered as an important clinical marker for predicting positive computed tomography findings. Also computed tomography is an important initial investigation to evaluate the various craniocerebral injury in trauma patients.


Assuntos
Lesões Encefálicas/diagnóstico por imagem , Traumatismos Craniocerebrais/diagnóstico por imagem , Acidentes por Quedas/estatística & dados numéricos , Acidentes de Trânsito/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Lesões Encefálicas/epidemiologia , Lesões Encefálicas/patologia , Criança , Pré-Escolar , Traumatismos Craniocerebrais/epidemiologia , Traumatismos Craniocerebrais/patologia , Estudos Transversais , Feminino , Escala de Coma de Glasgow , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Nepal/epidemiologia , Neuroimagem , Fraturas Cranianas/diagnóstico por imagem , Fraturas Cranianas/patologia , Centros de Atenção Terciária/estatística & dados numéricos , Tomografia Computadorizada por Raios X , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA