Assuntos
Adjuvantes Anestésicos/administração & dosagem , Pentobarbital/administração & dosagem , Ressuscitação/métodos , Animais , Asfixia Neonatal/complicações , Asfixia Neonatal/terapia , Dano Encefálico Crônico/etiologia , Dano Encefálico Crônico/prevenção & controle , Modelos Animais de Doenças , Humanos , Macaca mulattaRESUMO
OBJECTIVES: To determine the rate of magnetic resonance imaging (MRI)-detected noncystic white matter injury (WMI) in a prospective cohort of premature newborns, and to evaluate its associations with changes in clinical predictors of WMI over the study period. STUDY DESIGN: A prospective cohort of premature newborns (<33 weeks gestational age) was studied with MRI within 4 weeks of birth and near term-equivalent age. A pediatric neuroradiologist scored the severity of WMI on T1-weighted MRI according to published criteria. WMI was classified as none/mild or moderate/severe. Subjects with severe cystic WMI, periventricular hemorrhagic infarction, or motion artifact on MRI were excluded. Changes in clinical characteristics and predictors of WMI over the study period (1998-2011) were evaluated. Predictors of moderate/severe WMI, including birth year, were evaluated using multivariate logistic regression. RESULTS: Among 267 newborns, 45 (17%) had moderate/severe WMI. The rate of moderate/severe WMI decreased over the study period (P = .002, χ(2) test for trends). On multivariate logistic regression, the odds of moderate/severe WMI decreased by 11% for each birth year of the cohort (OR, 0.89; 95% CI, 0.81-0.98; P = .02). Prolonged exposure to indomethacin also was independently associated with reduced odds of moderate/severe WMI. CONCLUSION: The decreasing burden of MRI-detected moderate/severe noncystic WMI in our cohort of premature newborns is independent over time of changes in the known clinical predictors of WMI. Prolonged exposure to indomethacin is associated with reduced WMI.
Assuntos
Dano Encefálico Crônico/fisiopatologia , Recém-Nascido Prematuro , Imageamento por Ressonância Magnética/métodos , Substância Branca/lesões , Anti-Inflamatórios não Esteroides/administração & dosagem , Dano Encefálico Crônico/diagnóstico , Dano Encefálico Crônico/prevenção & controle , California , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Indometacina/administração & dosagem , Recém-Nascido , Modelos Logísticos , Masculino , Estudos Prospectivos , Fatores de Risco , Substância Branca/patologiaRESUMO
To prevent the damage, successful interventions were implemented to protect the child during the early years. As a result, 98% of children less than 5 years of age grew and developed according to WHO guidelines. This created a "domino effect" in older children reflected by the increased demands in education and health care followed by a period of rapid socioeconomic development. We can conclude that investment in prevention of undernutrition in the early years of life has been highly profitable. The example of Chile can be used as a model for other countries who still suffer from undernutrition and poverty.
Para prevenir el daño se implantaron exitosas intervenciones, destinada a proteger al niño durante los primeros períodos de la vida. Como resultado, el 98% de los menores de cinco años en el país, está creciendo y desarrollándose dentro de parámetros normales establecidos por la OMS. En los años sucesivos, el impacto (efecto dominó) fue repercutiendo en edades posteriores, exteriorizándose en el incremento de las demandas educacionales y de salud, que culminaron con un posterior período de rápido desarrollo social y económico. Se concluye que la inversión en la prevención de la desnutrición de los primeros períodos de la vida, ha sido altamente rentable y no comparable con ninguna otra. El ejemplo de lo ocurrido en Chile durante este periodo, puede ser de utilidad para otros países de la región que aún padecen de similares problemas nutricionales y de pobreza.
Assuntos
Criança , Fatores Socioeconômicos , Dano Encefálico Crônico/prevenção & controle , Transtornos da Nutrição Infantil/prevenção & controle , Criança , Saúde da Criança , Programas Nacionais de SaúdeAssuntos
Erros de Diagnóstico , Serviço Hospitalar de Emergência/legislação & jurisprudência , Imperícia/legislação & jurisprudência , Acidentes por Quedas , Acidentes de Trânsito , Adolescente , Anestesia Local , Ira , Ciclismo/lesões , Dano Encefálico Crônico/etiologia , Dano Encefálico Crônico/prevenção & controle , Criança , Pré-Escolar , Cicatriz/etiologia , Circuncisão Masculina , Emergências , Reações Falso-Negativas , Evolução Fatal , Feminino , Gangrena/etiologia , Gangrena/prevenção & controle , Deformidades Adquiridas da Mão/etiologia , Deformidades Adquiridas da Mão/prevenção & controle , Traumatismos da Mão/diagnóstico , Doença de Hodgkin/complicações , Doença de Hodgkin/diagnóstico , Humanos , Lactente , Recém-Nascido , Vértebras Lombares/lesões , Masculino , Dor/etiologia , Paraplegia/etiologia , Pênis/lesões , Pneumotórax/etiologia , Gravidez , Complicações na Gravidez , Radiografia , Recidiva , Luxação do Ombro/diagnóstico por imagem , Fraturas da Coluna Vertebral/diagnóstico por imagem , Infecções Estreptocócicas/diagnóstico , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Suturas/efeitos adversos , Transporte de Pacientes , Ferimentos Perfurantes/complicações , Adulto JovemRESUMO
AIMS: The aim of the present study was to evaluate the neuroprotective effects of environmental enrichment (EE), assessed by cognitive activity in the Morris water maze, and on brain oxidative status, through measurement of macromolecules damage, lipid peroxidation levels, total cellular thiols and antioxidant enzymes in hippocampus, striatum and cerebral cortex. MAIN METHODS: Adult male Wistar rats were submitted to the modified permanent bilateral occlusion of the common carotid arteries (2VO) method, with right common carotid artery being first occluded, and tested three months after the ischemic event. Cognitive and physical stimulation, named Environmental Enrichment, consisted of one-hour sessions run 3 times per week during 12weeks, following two different stimulation protocols: pre-ischemia and pre+post-ischemia. Rats were then tested for both reference and working spatial memory tasks in the water maze and later sacrificed for measurement of oxidative stress parameters. KEY FINDINGS: A significant cognitive deficit was found in both spatial tasks after hypoperfusion; this effect was reversed in the 2VO enriched group. Moreover, hippocampal oxidative damage and antioxidant enzyme activity were decreased by environmental enrichment. SIGNIFICANCE: These results suggest that both stimulation protocols exert a neuroprotective effect against the cognitive impairment and the reduction of biomarkers for oxidative damage caused by chronic cerebral hypoperfusion.
Assuntos
Dano Encefálico Crônico/prevenção & controle , Terapia Cognitivo-Comportamental , Doenças Neurodegenerativas/prevenção & controle , Doenças Neurodegenerativas/terapia , Estresse Oxidativo/fisiologia , Animais , Artérias Carótidas , Córtex Cerebral/patologia , Transtornos Cognitivos/prevenção & controle , Transtornos Cognitivos/terapia , Hipocampo/química , Masculino , Aprendizagem em Labirinto , Ratos , Ratos Wistar , Superóxido Dismutase/química , VasoconstriçãoAssuntos
Dano Encefálico Crônico/prevenção & controle , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/terapia , Animais , Biomarcadores/análise , Temperatura Corporal , Encéfalo/patologia , Ensaios Clínicos como Assunto , Terapia Combinada , Eletroencefalografia , Humanos , Recém-Nascido , Capacitação em Serviço , Imageamento por Ressonância Magnética , Exame Neurológico , Fármacos Neuroprotetores/uso terapêutico , Segurança do Paciente , Sistema de Registros , Fatores de Tempo , Transporte de PacientesRESUMO
Acute and long-term complications can occur in patients receiving radiation therapy. It has been suggested that cytoprotection might decrease the incidence and severity of therapy-related toxicity in these patients. Developing cerebellum is highly radiosensitive and for that reason it is a useful structure to test potential neuroprotective substances to prevent radiation induced abnormalities. Recent studies have shown that estrogen can rapidly modulate intracellular signalling pathways involved in cell survival. Thus, it has been demonstrated that estrogens mediate neuroprotection by promoting growth, cell survival and by preventing axonal pruning. The aim of this work was to evaluate the effect of the treatment with 17-ß-estradiol on the motor, structural and biochemical changes induced by neonatal ionizing radiation exposure, and to investigate the participation of nitric oxide and protein kinase C, two important intracellular messengers involved in neuronal activity. Our results show that perinatal chronic 17-ß-estradiol treatment partially protects against radiation-induced cerebellar disorganization and motor abnormalities. PKC and NOS activities could be implicated in its neuroprotective mechanisms. These data provide new evidence about the mechanisms underlying estrogen neuroprotection, which could have therapeutic relevance for patients treated with radiotherapy.
Assuntos
Dano Encefálico Crônico/tratamento farmacológico , Doenças Cerebelares/tratamento farmacológico , Estradiol/farmacologia , Fármacos Neuroprotetores/farmacologia , Lesões Experimentais por Radiação/tratamento farmacológico , Lesões Experimentais por Radiação/metabolismo , Animais , Animais Recém-Nascidos , Dano Encefálico Crônico/etiologia , Dano Encefálico Crônico/prevenção & controle , Doenças Cerebelares/etiologia , Doenças Cerebelares/prevenção & controle , Feminino , Raios gama , Masculino , Lesões Experimentais por Radiação/etiologia , Ratos , Ratos WistarRESUMO
Temporal lobe epilepsy is the most common form of epilepsy in humans. Oxidative stress is a mechanism of cell death induced by seizures. Antioxidant compounds have neuroprotective effects due to their ability to inhibit free radical production. The objectives of this work were to comparatively study the inhibitory action of antioxidants (ascorbic acid or alpha-tocopherol) on behavioral changes and brain damage induced by high doses of pilocarpine, aiming to further clarify the mechanism of action of these antioxidant compounds. In order to determinate neuroprotective effects, we studied the effects of ascorbic acid (250 or 500 mg/kg, i.p.) and alpha-tocopherol (200 or 400 mg/kg, i.p.) on the behavior and brain lesions observed after seizures induced by pilocarpine (400 mg/kg, i.p., P400 model) in rats. Ascorbic acid or alpha-tocopherol injections prior to pilocarpine suppressed behavioral seizure episodes. These findings suggested that free radicals can be produced during brain damage induced by seizures. In the P400 model, ascorbic acid and alpha-tocopherol significantly decreased cerebral damage percentage. Antioxidant compounds can exert neuroprotective effects associated with inhibition of free radical production. These results highlighted the promising therapeutic potential of ascorbic acid and alpha-tocopherol in treatments for neurodegenerative diseases.
Assuntos
Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Dano Encefálico Crônico/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Convulsões/prevenção & controle , alfa-Tocoferol/uso terapêutico , Animais , Dano Encefálico Crônico/etiologia , Dano Encefálico Crônico/patologia , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Masculino , Agonistas Muscarínicos , Pilocarpina , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/complicaçõesRESUMO
Temporal lobe epilepsy is the most common form of epilepsy in humans. Oxidative stress is a mechanism of cell death induced by seizures. Antioxidant compounds have neuroprotective effects due to their ability to inhibit free radical production. The objectives of this work were to comparatively study the inhibitory action of antioxidants (ascorbic acid or α-tocopherol) on behavioral changes and brain damage induced by high doses of pilocarpine, aiming to further clarify the mechanism of action of these antioxidant compounds. In order to determinate neuroprotective effects, we studied the effects of ascorbic acid (250 or 500 mg/kg, i.p.) and α-tocopherol (200 or 400 mg/kg, i.p.) on the behavior and brain lesions observed after seizures induced by pilocarpine (400 mg/kg, i.p., P400 model) in rats. Ascorbic acid or α-tocopherol injections prior to pilocarpine suppressed behavioral seizure episodes. These findings suggested that free radicals can be produced during brain damage induced by seizures. In the P400 model, ascorbic acid and α-tocopherol significantly decreased cerebral damage percentage. Antioxidant compounds can exert neuroprotective effects associated with inhibition of free radical production. These results highlighted the promising therapeutic potential of ascorbic acid and α-tocopherol in treatments for neurodegenerative diseases.
A epilepsia de lobo temporal é a mais comum forma de epilepsia em humanos. O estresse oxidativo é um dos mecanismos de morte celular induzida pelas crises convulsivas. Os compostos antioxidantes apresentam efeitos neuroprotetores devido à sua capacidade de inibir a produção de radicais livres. Os objetivos do presente trabalho foram estudar de forma comparativa a ação inibitória de antioxidantes (ácido ascórbico e α-tocoferol) sobre as alterações comportamentais e histopatológicas no hipocampo de ratos após convulsões induzidas pela pilocarpina. A fim de determinar os efeitos neuroprotetores destas drogas, o presente trabalho estudou os efeitos do ácido ascórbico (250 ou 500 mg/kg, i.p.) e do α-tocoferol (200 ou 400 mg/kg, i.p.) sobre o comportamento e as lesões cerebrais observados após convulsões induzidas pela pilocarpina (400 mg/kg, i.p., P400), em ratos. As injeções de ácido ascórbico ou α-tocoferol antes da administração de pilocarpina reduzem o número de animais que convulsionam. Estes achados sugerem que os radicais livres podem induzir o desenvolvimento de lesão cerebral durante as crises epilépticas. No modelo P400, o ácido ascórbico e o α-tocoferol, diminuem significativamente os danos cerebrais. Os compostos antioxidantes podem exercer efeitos neuroprotetores, e esses resultados podem estar associados à inibição da produção de radicais livres. Estes resultados sugerem um promissor potencial terapêutico tanto para o ácido ascórbico quanto para o α-tocoferol no tratamento de doenças neurodegenerativas.
Assuntos
Animais , Masculino , Ratos , Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Dano Encefálico Crônico/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Convulsões/prevenção & controle , alfa-Tocoferol/uso terapêutico , Dano Encefálico Crônico/etiologia , Dano Encefálico Crônico/patologia , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Agonistas Muscarínicos , Pilocarpina , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/complicaçõesRESUMO
Older patients with diabetes have a high risk of vascular complications. They have an increase of approximately 3 times for developing stroke compared with subjects without diabetes. In addition, up to 75-80% of deaths in diabetic patients are associated with major cardiovascular events including stroke. The risk of stroke is high within 5 years of diagnosis for type 2 diabetes is 9% (mortality 21%), that is more than doubles the rate for the general population. From observational registries in a collaborative stroke study in Mexico, we analyzed clinical data, risk factors, and outcome of 1182 diabetic patients with cerebral ischemia, with focus in elderly subjects. There was a high frequency of hyperglycemia during the acute phase of stroke: the median value was 140 mg/dL and 40% had values higher than 180 mg/dL. Clinical outcome was usually unfavorable in elderly stroke patients with diabetes: case fatality rate was 30% at 30 days and survivors had moderate to severe disability, usually as consequence of the propensity to develop more systemic medical complications during hospital stay. Primary stroke prevention studies in patients with diabetes reveal that tight control of glucose is not associated with reduction in stroke risk. Therefore, proper control of other vascular risk factors is mandatory in patients with diabetes, in particular of arterial hypertension.
Assuntos
Transtornos Cerebrovasculares/epidemiologia , Diabetes Mellitus/epidemiologia , Angiopatias Diabéticas/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Glicemia/análise , Dano Encefálico Crônico/epidemiologia , Dano Encefálico Crônico/etiologia , Dano Encefálico Crônico/prevenção & controle , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/etiologia , Isquemia Encefálica/terapia , Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/fisiopatologia , Transtornos Cerebrovasculares/prevenção & controle , Transtornos Cerebrovasculares/terapia , Comorbidade , Diabetes Mellitus/fisiopatologia , Angiopatias Diabéticas/fisiopatologia , Angiopatias Diabéticas/prevenção & controle , Angiopatias Diabéticas/terapia , Suscetibilidade a Doenças , Feminino , Humanos , Resistência à Insulina , Masculino , Síndrome Metabólica/epidemiologia , México/epidemiologia , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Prevenção Secundária , Resultado do TratamentoRESUMO
Cerebral malaria (CM) is a life-threatening complication of malaria caused by Plasmodium falciparum, and it claims around two million lives a year, mainly those of children in sub-Saharan Africa. A number of works, particularly in murine models of CM, showed that several mediators are involved in the development of the disease, including monocytes, T lymphocytes, cytokines, chemokines, platelets, nitric oxide scavengers and heme, among others, but a comprehensive understanding of the pathogenesis of this complication is still lacking. This overview critically analyzes and discusses the definition, clinical features, neurocognitive outcomes and pathogenesis of human CM. We focused on the relationship between clinical and laboratory features and the diagnosis and prognosis of the complication showing indicators of poor prognosis and emphasizing the need of establishing predictive scores to estimate, on admission, the likelihood of any malarial patient to develop neurological complications. The potential development of a mathematical model for early prediction of CM through neurological assessment using the SHIRPA protocol in Plasmodium berghei ANKA-infected susceptible mice is shown. High positive predictive values (>89%) on days 5 and 6 of infection, observed for some generated SHIRPA scores, indicate the possibility of early detection of mice with a high probability of developing CM.
Assuntos
Malária Cerebral/epidemiologia , Exame Neurológico , África Subsaariana/epidemiologia , Animais , Antimaláricos/uso terapêutico , Sudeste Asiático/epidemiologia , Dano Encefálico Crônico/epidemiologia , Dano Encefálico Crônico/etiologia , Dano Encefálico Crônico/prevenção & controle , Criança , Coma/etiologia , Diagnóstico Precoce , Humanos , Hipoglicemia/etiologia , Malária Cerebral/complicações , Malária Cerebral/diagnóstico , Malária Cerebral/fisiopatologia , Malária Cerebral/prevenção & controle , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Exame Físico , Prognóstico , Medição de Risco , Sensibilidade e Especificidade , Especificidade da EspécieRESUMO
Substances that promote the growth and maturation of oligodendrocytes and their precursors might protect against white matter injury. We suggest that neuroprotection can also be provided by such modulators of fetal and neonatal inflammatory responses as antiinflammatory cytokines, cytokine-binding proteins, and cytokine-receptor blockers. We briefly describe inflammatory responses in the fetus and newborn and show how they might contribute to brain damage. We conclude with the possibility that so-called biological response modifiers, which are drugs that modulate these inflammatory responses, might reduce the risk of brain damage and disabilities.
Assuntos
Dano Encefálico Crônico/prevenção & controle , Fatores Imunológicos/uso terapêutico , Doenças do Prematuro/tratamento farmacológico , Pessoas com Deficiência Mental , Dano Encefálico Crônico/etiologia , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/etiologiaRESUMO
We have investigated the mechanisms of hypoxic brain cell injury in the immature animal by examining (1) the role of excitatory amino acid neurotransmitter receptors, (2) the receptor-mediated increase in intracellular Ca2+, and (3) the generation of oxygen free radicals. We examined the effect of brain tissue hypoxia on the NMDA receptor-ion channel complex including the glutamate, Mg2+, spermine, CPP, and the non-NMDA receptor kainate sites. Brain tissue hypoxia resulted in modification of the NMDA receptor ion channel and its modulatory sites. Hypoxia increased the affinity of both the ion channel and the glutamate recognition site. Pretreatment of animals with the glutamate antagonist CPP prevented hypoxia-induced modification of the channel. Similarly, pretreatment of animals with Mg2+, a blocker of the NMDA receptor ion channel, prevented the hypoxia-induced modification of the receptor. In addition, an increased agonist-dependent entry of Ca2+ into synaptosomes was observed in hypoxic animals compared with normoxic animals. Increased free radical generation in the cerebral cortex during hypoxia was demonstrated using spin labeling technique and electron spin resonance spectroscopy. We conclude that hypoxia-induced modification of the NMDA receptor-ion channel complex leads to increased intracellular Ca2+ potentiating free radical generation and resulting in hypoxic cell injury.
Assuntos
Asfixia Neonatal/fisiopatologia , Dano Encefálico Crônico/fisiopatologia , Animais , Asfixia Neonatal/prevenção & controle , Encéfalo/fisiopatologia , Dano Encefálico Crônico/prevenção & controle , Hipóxia Celular/fisiologia , Feminino , Radicais Livres , Humanos , Recém-Nascido , Gravidez , Espécies Reativas de Oxigênio/metabolismo , Receptores de N-Metil-D-Aspartato/fisiologiaRESUMO
The role of glutamic acid (glutamate) in the pathogenesis of stroke is now fairly well established. As a result, many drugs which act on glutamate receptors are currently under investigation for their ability to prevent the damage induced by glutamate under ischaemic conditions. The efficacy of these compounds in protecting central neurones from the effects of stroke may be indicative of the importance of the role that glutamate plays in this process.
Assuntos
Transtornos Cerebrovasculares/fisiopatologia , Ácido Glutâmico/fisiologia , Fármacos Neuroprotetores/uso terapêutico , Dano Encefálico Crônico/fisiopatologia , Dano Encefálico Crônico/prevenção & controle , Transtornos Cerebrovasculares/tratamento farmacológico , Humanos , Receptores de Glutamato/efeitos dos fármacos , Receptores de Glutamato/fisiologiaRESUMO
In a randomized prospective trial, we studied the effect of early high-dose phenobarbital treatment on the early (intraventricular hemorrhage) and late (neurodevelopmental abnormalities) manifestations of hypoxic-ischemic encephalopathy in preterm infants weighing 1500 g or less at birth. The first intravenous dose of 15 mg/kg was given at a mean age of 110 minutes, followed by 15 mg/kg after 4 hours and then by 5 mg/kg at 24-hour intervals for 5 days. The overall incidence of intraventricular hemorrhage was 32% in treated and 46% in control infants, a nonsignificant difference. An ultrasound brain scan at 9 months old revealed no significant difference in the incidence of ventricular dilatation between treated (19%) and control (29%) infants. At 27 months, a similar incidence of mild (10%) and severe (10%) neurodevelopmental handicaps was found in both treated and control groups. Since beneficial effects could not be documented by any of the criteria used, we conclude that routine administration of phenobarbital to low birth weight infants is not justified.
Assuntos
Dano Encefálico Crônico/prevenção & controle , Isquemia Encefálica/complicações , Hipóxia/complicações , Recém-Nascido de Baixo Peso , Doenças do Prematuro/complicações , Fenobarbital/administração & dosagem , Dano Encefálico Crônico/etiologia , Hemorragia Cerebral/prevenção & controle , Deficiências do Desenvolvimento/etiologia , Deficiências do Desenvolvimento/prevenção & controle , Esquema de Medicação , Seguimentos , Humanos , Recém-Nascido , Leucomalácia Periventricular/prevenção & controle , Exame Neurológico , Estudos Prospectivos , Distribuição AleatóriaRESUMO
PIP: Dr. Holger Hansen comments on an article by Buist and Jhavarie on maternal hyperphenylalaninemia. The noted that the condition causes prenatal brain damage and recommended a low-phenylalanine diet during pregnancy for women with blood phyenylalanine levels greater than 10 to 15 mg per 100 ml. In the same Journal of Pediatrics issue in which their article appeared, there was a report of a mother with hyperphenylalaninemia who had 2 normal children. In 8 women out of 20 with maternal hyperphenylalaninemia, phenylalanine levels were greater than 10 mg per 100 ml. 12 normal children were born and 10 mentally retarded children were born. Dr. Hansen suggests that that termination of pregnancy in hyperphenylalaninemic mothers should not continue to be the treatment of choice. Buist and Jhaveri respond that Dr. Hansen does not provide all the data and that there are reports in which all the children of affected mothers were severely brain damaged. They contend that the controlled use of some form of phenylalanine-restricted diet during pregnancy should be the treatment of choice.^ieng