RESUMO
BACKGROUND: 123I-iomazenil (IMZ) single-photon emission computed tomography (SPECT) is a tool for evaluating epileptic foci and brain damage. To apply the method to children, information regarding the age-specific expression of benzodiazepine receptors (BDZ-Rs) is required. Unfortunately, there is no information currently available for children <2 years of age. METHODS: We used IMZ SPECT once in infants aged 3-8 months and again at 2 years of age in order to describe the maturational changes in BDZ-R distribution. RESULTS: No neurological deficits were found in any of the infants at the first examination. The BDZ-Rs were more dominantly distributed in the occipital lobe than in the frontal lobe before the age of 2 years. The frontal-occipital gradients of the distribution were obvious in children <8 months of age. Magnetic resonance imaging showed a spreading of myelination toward the frontal lobes simultaneously with BDZ-R expression. CONCLUSION: Information regarding the alteration in the BDZ-R distribution pattern is useful when assessing infantile epilepsy and brain injury. The age-related pattern of BDZ-R distribution could correspond with myelination, cerebral blood flow, metabolism and behavioral development.
Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Receptores de GABA-A/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único , Autorradiografia/métodos , Benzodiazepinas/metabolismo , Pré-Escolar , Feminino , Flumazenil/análogos & derivados , Flumazenil/metabolismo , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/metabolismo , Humanos , Lactente , Radioisótopos do Iodo/metabolismo , Masculino , Lobo Occipital/diagnóstico por imagem , Lobo Occipital/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único/métodosRESUMO
As limited amounts of data are available regarding thrombolytic therapy for patients taking novel oral anticoagulants, thrombolytic therapy is not recommended in such cases. Here, we report an acute stroke patient taking rivaroxaban who received intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA). An 80-year-old man with a history of nonvalvular atrial fibrillation, who had been receiving 10 mg of rivaroxaban showed abrupt onset of aphasia and right hemiparesis. National Institutes of Health Stroke Scale score was 10. Onset of neurologic deficits occurred 4 hours after the last dose of rivaroxaban. Clinical data on admission were as follows: blood pressure, 170/90 mm Hg; prothrombin time (PT), 22.6 seconds (control, 12.9 seconds); international normalized ratio, 2.03; activated partial thromboplastin time, 46 seconds (normal, 23-32 seconds); and creatinine level, 1.11 mg/dL. Magnetic resonance angiography revealed occlusion of the superior trunk of the left middle cerebral artery. Intravenous infusion of .6 mg/kg of rt-PA (total dose, 36 mg) was performed 6 hours after the last rivaroxaban administration with informed consent. The neurologic deficit improved during infusion of rt-PA. Repeat brain computed tomography showed left frontal cortical infarction without hemorrhagic changes. In the case of rivaroxaban, it is difficult to accurately determine the drug activity. As the anticoagulant activity of rivaroxaban can be estimated from its pharmacokinetics and PT, it is clinically important to obtain accurate information about the timing of medication and blood sampling.
Assuntos
Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/uso terapêutico , Fibrinolíticos/administração & dosagem , Morfolinas/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Tiofenos/uso terapêutico , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/administração & dosagem , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Coagulação Sanguínea/efeitos dos fármacos , Angiografia Cerebral/métodos , Imagem de Difusão por Ressonância Magnética , Monitoramento de Medicamentos/métodos , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/farmacocinética , Fibrinolíticos/efeitos adversos , Humanos , Infusões Intravenosas , Angiografia por Ressonância Magnética , Masculino , Morfolinas/efeitos adversos , Morfolinas/farmacocinética , Valor Preditivo dos Testes , Tempo de Protrombina , Proteínas Recombinantes/administração & dosagem , Fatores de Risco , Rivaroxabana , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Tiofenos/efeitos adversos , Tiofenos/farmacocinética , Terapia Trombolítica/efeitos adversos , Ativador de Plasminogênio Tecidual/efeitos adversos , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
INTRODUCTION: Activated microglia produce neurotoxic factors, including pro-inflammatory cytokines and nitric oxide (NO), in response to neuronal destruction. Therapeutic suppression of microglial release of these factors by various approaches including hypothermia is considered to be neuroprotective after severe brain damage. We examined the effects of hypothermic culture on the production of pro- and anti-inflammatory cytokines and NO in ex vivo microglia that were derived from mice with hypoxic-ischemic (HI) brain injury, through the stimulation of toll-like receptors (TLRs) that play significant roles in the pathological processes underlying a sterile central nervous system injury. MATERIAL AND METHODS: Two-day-old mice underwent the right common carotid artery ligation followed by 6% oxygen for 30 min, and thereafter were placed at 37°C for 24 h, after which microglia were isolated and then cultured with TLR2 and TLR4 agonists at 33°C and 37°C. Cytokine and NO levels in culture supernatants were measured. RESULTS: Compared with 37°C, hypothermia (33°C) reduced the production of tumour necrosis factor-alpha (TNF-α: a pro-inflammatory cytokine) at 6 h and interleukin-10 (IL-10: an anti-inflammatory cytokine) and NO at 48 h. CONCLUSIONS: In TLR-activated microglia that were derived from mice with HI brain injury, hypothermia reduced the production of TNF-α, IL-10, and NO temporally, a clinically relevant finding suggesting that neuroprotection conferred by therapeutic hypothermia is related to attenuation of early-phase and late-phase inflammatory factors as well as that of late-phase anti-inflammatory factor(s) released from microglia.
Assuntos
Citocinas/biossíntese , Hipertermia Induzida , Hipóxia-Isquemia Encefálica/metabolismo , Microglia/metabolismo , Óxido Nítrico/biossíntese , Animais , Separação Celular , Células Cultivadas , Modelos Animais de Doenças , Feminino , Masculino , CamundongosRESUMO
Glioblastomas are the most aggressive brain tumors. Glioblastoma stem cells (GSCs) are thought to be responsible for the recurrence, chemoresistance, and poor prognosis of glioblastoma. Fatty acid binding protein 7 (FABP7), which is a cellular chaperone for a variety of omega-3 fatty acids, is a known marker for neural stem cells. In this study, using a newly developed anti-FABP7 antibody and patient-derived GSC lines, we evaluated the expression of FABP7 in GSCs. Using immunocytochemistry, Western blotting, and qPCR analyses, FABP7 was found to be highly enriched in GSCs and its localization was found in cytosol and nuclei. FABP7 expression was significantly downregulated in differentiated GSCs induced by the addition of serum. In the glioma surgical specimens, FABP7 was highly expressed in the majority of glioblastoma. Double immunostaining for FABP7 and Sox2 showed that FABP7(+) Sox2(+) tumor cells were significantly increased in glioblastoma (grade IV) compared with diffuse astrocytoma (grade II) and anaplastic astrocytoma (grade III). Our data introduces FABP7 as a marker for GSCs and further highlights its possible significance for glioma diagnosis and treatment.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Proteínas de Transporte/metabolismo , Glioma/metabolismo , Células-Tronco Neoplásicas/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proteína 7 de Ligação a Ácidos Graxos , Feminino , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/patologiaRESUMO
A 31-year-old healthy male presented with a rare case of cerebral arteriovenous malformation (AVM) manifesting as repeated ischemic attacks and cerebral infarction causing left sensori-motor disturbance. Neuroimaging revealed cerebral infarction in the right thalamus as well as right occipital AVM without bleeding. The AVM was mainly fed by the right angular artery, and the right posterior cerebral artery (PCA) showed mild stenosis and segmental dilation at the P(2)-P(3) portion. After referral to our hospital, transient ischemic attacks causing left homonymous hemianopsia, and left arm and leg numbness were frequently recognized. Additional imaging revealed a new ischemic lesion in the occipital lobe, and repeated cerebral angiography showed right PCA occlusion at the P(2)-P(3) segment. Cerebral AVM presenting with cerebral infarction due to occlusion of feeding arteries is rare. In our case, intimal injury due to increased blood flow or spontaneous dissection of the artery were possible causes. We should monitor any changes in the architecture and rheology of the feeding vessels during the clinical course to prevent ischemic complications.
Assuntos
Infarto da Artéria Cerebral Posterior/diagnóstico , Malformações Arteriovenosas Intracranianas/diagnóstico , Ataque Isquêmico Transitório/diagnóstico , Lobo Occipital/irrigação sanguínea , Adulto , Angiografia Cerebral , Dominância Cerebral/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Exame Neurológico , Tálamo/irrigação sanguínea , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: Focal brain cooling is effective for suppression of epileptic seizures, but it is unclear if seizures can be suppressed without a substantial influence on normal neurologic function. To address the issue, a thermoelectrically driven cooling system was developed and applied in free-moving rat models of focal seizure and epilepsy. METHODS: Focal seizures limited to the unilateral forelimb were induced by local application of a penicillin G solution or cobalt powder to the unilateral sensorimotor cortex. A proportional integration and differentiation (PID)-controlled, thermoelectrically driven cooling device (weight of 11 g) and bipolar electrodes were chronically implanted on the eloquent area (on the epileptic focus) and the effects of cooling (20, 15, and 10°C) on electrocorticography, seizure frequency, and neurologic changes were investigated. KEY FINDINGS: Cooling was associated with a distinct reduction of the epileptic discharges. In both models, cooling of epileptic foci significantly improved both seizure frequency and neurologic functions from 20°C down to 15°C. Cooling to 10°C also suppressed seizures, but with no further improvement in neurologic function. Subsequent investigation of sensorimotor function revealed significant deterioration in foot-fault tests and the receptive field size at 15°C. SIGNIFICANCE: Despite the beneficial effects in ictal rats, sensorimotor functions deteriorated at 15°C, thereby suggesting a lower limit for the therapeutic temperature. These results provide important evidence of a therapeutic effect of temperatures from 20 to 15°C using an implantable, hypothermal device for focal epilepsy.
Assuntos
Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/terapia , Epilepsia/fisiopatologia , Epilepsia/terapia , Hipotermia Induzida/métodos , Córtex Motor/fisiopatologia , Animais , Temperatura Corporal/fisiologia , Ondas Encefálicas/efeitos dos fármacos , Ondas Encefálicas/fisiologia , Cobalto/toxicidade , Convulsivantes/toxicidade , Modelos Animais de Doenças , Eletrônica Médica/instrumentação , Eletrônica Médica/métodos , Hipotermia Induzida/efeitos adversos , Hipotermia Induzida/instrumentação , Masculino , Penicilina G/toxicidade , Ratos , Ratos WistarRESUMO
Reactive gliosis, in which astrocytes as well as other types of glial cells undergo massive proliferation, is a common hallmark of all brain pathologies. Brain-type fatty acid-binding protein (FABP7) is abundantly expressed in neural stem cells and astrocytes of developing brain, suggesting its role in differentiation and/or proliferation of glial cells through regulation of lipid metabolism and/or signaling. However, the role of FABP7 in proliferation of glial cells during reactive gliosis is unknown. In this study, we examined the expression of FABP7 in mouse cortical stab injury model and also the phenotype of FABP7-KO mice in glial cell proliferation. Western blotting showed that FABP7 expression was increased significantly in the injured cortex compared with the contralateral side. By immunohistochemistry, FABP7 was localized to GFAP(+) astrocytes (21% of FABP7(+) cells) and NG2(+) oligodendrocyte progenitor cells (62%) in the normal cortex. In the injured cortex there was no change in the population of FABP7(+)/NG2(+) cells, while there was a significant increase in FABP7(+)/GFAP(+) cells. In the stab-injured cortex of FABP7-KO mice there was decrease in the total number of reactive astrocytes and in the number of BrdU(+) astrocytes compared with wild-type mice. Primary cultured astrocytes from FABP7-KO mice also showed a significant decrease in proliferation and omega-3 fatty acid incorporation compared with wild-type astrocytes. Overall, these data suggest that FABP7 is involved in the proliferation of astrocytes by controlling cellular fatty acid homeostasis.