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1.
Brain Behav Immun ; 50: 87-100, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26122280

RESUMO

Activation of purinergic receptors by extracellular ATP (eATP) released from injured cells has been implicated in the pathogenesis of many neuronal disorders. The P2X7 receptor (P2X7R), an ion-selective purinergic receptor, is associated with microglial activation and paracrine signaling. However, whether ATP and P2X7R are involved in radiation-induced brain injury (RBI) remains to be determined. Here, we found that the eATP level was elevated in the cerebrospinal fluid (CSF) of RBI patients and was associated with the clinical severity of the disorder. In our experimental model, radiation treatment increased the level of eATP in the supernatant of primary cultures of neurons and glial cells and in the CSF of irradiated mice. In addition, ATP administration activated microglia, induced the release of the inflammatory mediators such as cyclooxygenase-2, tumor necrosis factor α and interleukin 6, and promoted neuronal apoptosis. Furthermore, blockade of ATP-P2X7R interaction using P2X7 antagonist Brilliant Blue G or P2X7 knockdown suppressed radiation-induced microglial activation and proliferation in the hippocampus, and restored the spatial memory of irradiated mice. Finally, we found that the PI3K/AKT and nuclear factor κB mediated pathways were downstream of ATP-P2X7R signaling in RBI. Taken together, our results unveiled the critical role of ATP-P2X7R in brain damage in RBI, suggesting that inhibition of ATP-P2X7R axis might be a potential strategy for the treatment of patients with RBI.


Assuntos
Trifosfato de Adenosina/efeitos adversos , Lesões Encefálicas/metabolismo , Microglia/metabolismo , Comunicação Parácrina , Lesões por Radiação/metabolismo , Radioterapia/efeitos adversos , Receptores Purinérgicos P2X7/metabolismo , Trifosfato de Adenosina/líquido cefalorraquidiano , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/efeitos da radiação , Lesões Encefálicas/líquido cefalorraquidiano , Lesões Encefálicas/etiologia , Células Cultivadas , Feminino , Humanos , Inflamação/metabolismo , Masculino , Camundongos , Microglia/efeitos dos fármacos , Microglia/efeitos da radiação , Lesões por Radiação/líquido cefalorraquidiano , Lesões por Radiação/complicações , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação
2.
Int J Radiat Oncol Biol Phys ; 89(3): 607-14, 2014 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-24803034

RESUMO

PURPOSE: To examine whether cerebrospinal fluid biomarkers for neuroaxonal damage, neuroglial activation, and amyloid ß-related processes could characterize the neurochemical response to cranial radiation. METHODS AND MATERIALS: Before prophylactic cranial irradiation (PCI) of patients with small cell lung cancer, each patient underwent magnetic resonance imaging of the brain, lumbar puncture, and Mini-Mental State Examination of cognitive function. These examinations were repeated at approximately 3 and 12 months after radiation. RESULTS: The major findings were as follows. (1) Cerebrospinal fluid markers for neuronal and neuroglial injury were elevated during the subacute phase after PCI. Neurofilament and T-tau increased 120% and 50%, respectively, after PCI (P<.05). The same was seen for the neuroglial markers YKL-40 and glial fibrillary acidic protein, which increased 144% and 106%, respectively, after PCI (P<.05). (2) The levels of secreted amyloid precursor protein-α and -ß were reduced 44% and 46%, respectively, 3 months after PCI, and the levels continued to decrease as long as 1 year after treatment (P<.05). (3) Mini-Mental State Examination did not reveal any cognitive decline, indicating that a more sensitive test should be used in future studies. CONCLUSION: In conclusion, we were able to detect radiation therapy-induced changes in several markers reflecting neuronal injury, inflammatory/astroglial activation, and altered amyloid precursor protein/amyloid ß metabolism, despite the low number of patients and quite moderate radiation doses (20-30 Gy). These changes are hypothesis generating and could potentially be used to assess the individual risk of developing long-term symptoms of chronic encephalopathy after PCI. This has to be evaluated in large studies with extended clinical follow-up and more detailed neurocognitive assessments.


Assuntos
Biomarcadores/líquido cefalorraquidiano , Irradiação Craniana/efeitos adversos , Neuroglia/efeitos da radiação , Neurônios/efeitos da radiação , Lesões por Radiação/líquido cefalorraquidiano , Adipocinas/líquido cefalorraquidiano , Idoso , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Precursor de Proteína beta-Amiloide/líquido cefalorraquidiano , Neoplasias Encefálicas/prevenção & controle , Neoplasias Encefálicas/secundário , Estudos de Casos e Controles , Proteína 1 Semelhante à Quitinase-3 , Cognição/efeitos da radiação , Transtornos Cognitivos/diagnóstico , Suscetibilidade a Doenças/líquido cefalorraquidiano , Feminino , Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano , Humanos , Lectinas/líquido cefalorraquidiano , Neoplasias Pulmonares , Masculino , Pessoa de Meia-Idade , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Testes Neuropsicológicos , Fragmentos de Peptídeos/líquido cefalorraquidiano , Estudos Prospectivos , Carcinoma de Pequenas Células do Pulmão/prevenção & controle , Carcinoma de Pequenas Células do Pulmão/secundário , Proteínas tau/líquido cefalorraquidiano
3.
Am J Hematol ; 79(4): 291-3, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16044440

RESUMO

Extramedullary meningeal hematopoiesis (EMH) represents an uncommon finding after stem-cell transplantation. We describe the case of an allogeneic bone marrow transplantation (BMT) recipient who developed EMH 1 month after radiation myelitis had been diagnosed. A 39-year-old man with multiple myeloma underwent matched unrelated BMT following a myeloablative conditioning regimen of cyclophosphamide and total-body irradiation (200 cGyx6). This was followed by delivery of 40 Gy of involved-field radiation to an extramedullary plasmacytoma compressing the spinal cord. Although transplantation went extremely well, the patient developed radiation myelitis 7 months after transplantation, and EMH ensued 1 month later. Because the patient was not in a disease state known to cause EMH, it is tempting to speculate that radiation-related neural injuries might cause donor cells to migrate to the central nervous system.


Assuntos
Hematopoese Extramedular/efeitos da radiação , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Mielite/etiologia , Lesões por Radiação/etiologia , Medula Espinal/efeitos da radiação , Adulto , Terapia Combinada , Humanos , Masculino , Meninges/fisiologia , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/radioterapia , Mielite/líquido cefalorraquidiano , Lesões por Radiação/líquido cefalorraquidiano , Irradiação Corporal Total/efeitos adversos
4.
Neurology ; 61(4): 537-40, 2003 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-12939432

RESUMO

The authors report the case of a 60-year-old man with acromegaly, who developed narcolepsy 2 weeks after completing radiotherapy for a pituitary adenoma. Cataplexy and sleepiness were predominant symptoms. Onset of narcolepsy is unusual at this age and the temporal relationship following radiotherapy suggests this treatment was implicated. His CSF hypocretin levels were normal, indicating other factors may be important in his narcolepsy.


Assuntos
Acromegalia/radioterapia , Peptídeos e Proteínas de Sinalização Intracelular , Narcolepsia/etiologia , Irradiação Hipofisária/efeitos adversos , Lesões por Radiação/etiologia , Proteínas de Transporte/líquido cefalorraquidiano , Estimulantes do Sistema Nervoso Central/uso terapêutico , Humanos , Masculino , Mazindol/uso terapêutico , Pessoa de Meia-Idade , Narcolepsia/líquido cefalorraquidiano , Narcolepsia/tratamento farmacológico , Neuropeptídeos/líquido cefalorraquidiano , Orexinas , Lesões por Radiação/líquido cefalorraquidiano , Lesões por Radiação/tratamento farmacológico , Paralisia do Sono/etiologia
5.
Bone Marrow Transplant ; 12(6): 615-9, 1993 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8136745

RESUMO

The material from 59 and 134 cerebrospinal fluid (CSF) samples, taken in the week prior to grafting and during the first 100 days after grafting respectively, were examined from 37 children undergoing allogeneic BMT. All CSF samples were obtained from lumbar punctures performed for regular administration of methotrexate (MTX). Prior to bone marrow transplantation (BMT) the increased protein levels and increased cell numbers noted in two children were probably caused by arachnoiditis from MTX administration 5 days earlier. After BMT, cell numbers increased in 54% of children and in 27% of children increased protein levels were found in the CSF. No correlation with clinical findings including neurological findings, infections and prior intrathecal MTX administration was found. The CSF changes observed are probably induced by the conditioning regimen (i.e. cyclophosphamide and total body irradiation). We conclude that the normal ranges for CSF components seen in healthy individuals do not apply in BMT recipients during the first 100 days after grafting.


Assuntos
Transplante de Medula Óssea , Leucemia-Linfoma Linfoblástico de Células Precursoras/líquido cefalorraquidiano , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Adolescente , Aracnoidite/líquido cefalorraquidiano , Aracnoidite/induzido quimicamente , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/patologia , Transplante de Medula Óssea/fisiologia , Lesões Encefálicas/líquido cefalorraquidiano , Lesões Encefálicas/etiologia , Neoplasias Encefálicas/prevenção & controle , Líquido Cefalorraquidiano/citologia , Proteínas do Líquido Cefalorraquidiano/metabolismo , Criança , Pré-Escolar , Terapia Combinada , Feminino , Humanos , Masculino , Metotrexato/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Lesões por Radiação/líquido cefalorraquidiano , Lesões por Radiação/etiologia , Transplante Homólogo
6.
J Neurol Neurosurg Psychiatry ; 37(10): 1177-80, 1974 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-4443812

RESUMO

Radiation myelopathy is a well-known complication of irradiation therapy of neoplasms in the vicinity of the spinal cord. Most earlier authors have stressed the association of a normal myelogram and normal CSF protein level with this condition. One case of radiation myelopathy with a myelogram simulating intramedullary neoplasm and with extremely high CSF protein concentration is presented. Six months after myelography necropsy revealed severe atrophy of the previously thickened lower cervical spinal cord. The pathogenetic mechanisms are discussed.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Radioisótopos de Cobalto/efeitos adversos , Neoplasias Faríngeas/radioterapia , Lesões por Radiação/patologia , Radioterapia/efeitos adversos , Doenças da Medula Espinal/etiologia , Medula Espinal/patologia , Atrofia , Proteínas do Líquido Cefalorraquidiano/análise , Feminino , Humanos , Pessoa de Meia-Idade , Mielografia , Lesões por Radiação/líquido cefalorraquidiano , Lesões por Radiação/diagnóstico por imagem , Doenças da Medula Espinal/líquido cefalorraquidiano , Doenças da Medula Espinal/diagnóstico por imagem
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