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1.
Int J Radiat Oncol Biol Phys ; 110(2): 337-347, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33412257

RESUMO

PURPOSE: The corpus callosum (CC) and intrahemispheric white matter tracts (IHWM) subserve critical aspects of attention and processing speed. We analyzed imaging biomarkers of microstructural injury within these regions and association with attention and processing speed performance before and after radiation therapy in primary brain tumor patients. METHODS AND MATERIALS: In a prospective clinical trial, 44 primary brain tumor patients underwent cognitive testing and magnetic resonance imaging/diffusion-weighted imaging at baseline (pre-radiation therapy) and 3-, 6-, and 12-months post-radiation therapy. CC (subregions, total) and IHWM tracts (left/right without CC, total) were autosegmented; tumor, tumor bed, and edema were censored. Biomarkers included volume changes (cm3), mean diffusivity ([MD]; higher values indicate white matter injury), fractional anisotropy ([FA]; lower values indicate white matter injury). Reliable-change indices measured changes in attention (Weschler Adult Intelligence Scale [WAIS-IV] digits-forward; Delis-Kaplan Executive Function System Trail Making [D-KEFS-TM] visual-scanning), and processing speed (WAIS-IV coding; D-KEFS-TM number-sequencing, letter-sequencing), accounting for practice effects. Linear mixed-effects models evaluated associations between mean radiation dose and biomarkers (volume, MD, FA) and imaging biomarkers and neurocognitive performance. Statistics were corrected for multiple comparisons. RESULTS: Processing speed declined at 6 months following radiation therapy (number sequencing, letter sequencing; P < .04). Seizures and antiepileptic drug therapy were associated with lower visual-scanning attention reliable-change indices at 6 months (P = .039). Higher radiation dose correlated with smaller midanterior CC volume (P = .023); lower FA in posterior CC, anterior CC, and total CC (all P < .03); and higher MD in anterior CC (P = .012). Smaller midanterior CC and left IHWM volume correlated with worse processing speed (coding, letter-sequencing, number-sequencing; all P < .03). Higher FA in right, left, and total IHWM correlated with better coding scores (all P < .01). Lower FA in total IHWM (P = .009) was associated with worse visual-scanning attention scores. Higher FA in midposterior CC (P = .029) correlated with better digits-forward attention scores. CONCLUSIONS: The CC demonstrated radiation dose-dependent atrophy and WM injury. Microstructural injury within the CC and IHWM was associated with attention and processing speed decline after radiation therapy. These areas represent possible avoidance regions for preservation of attention and processing speed.


Assuntos
Atenção/efeitos da radiação , Neoplasias Encefálicas/radioterapia , Cognição/efeitos da radiação , Corpo Caloso/efeitos da radiação , Lesões por Radiação/complicações , Substância Branca/efeitos da radiação , Adulto , Idoso , Anisotropia , Anticonvulsivantes/farmacologia , Atrofia , Atenção/efeitos dos fármacos , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos da radiação , Neoplasias Encefálicas/diagnóstico por imagem , Cognição/efeitos dos fármacos , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Imagem de Difusão por Ressonância Magnética , Função Executiva/efeitos da radiação , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/patologia , Convulsões/tratamento farmacológico , Fatores de Tempo , Teste de Sequência Alfanumérica , Escalas de Wechsler , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adulto Jovem
2.
Adv Clin Exp Med ; 29(3): 331-337, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32237285

RESUMO

BACKGROUND: More than half of pediatric tumors of central nervous system (CNS) primarily originate in the posterior fossa and are conventionally treated with radiation therapy (RT). OBJECTIVES: The objective of this study was to establish whether corpus callosum volumes (CCV) and whole brain volumes (WBV) are correlated and to determine the impact of whole-brain lowvs high-dose RT on brain parenchymal volume loss as assessed using each technique. MATERIAL AND METHODS: Of the 30 identified children (6-12 years) with newly diagnosed posterior fossa tumors treated with cranial RT, including focal and whole-brain RT, suitable imaging was obtained for 23. Radiotherapy regimens were the following: no whole-brain RT (Group 1, n = 7), low-dose whole-brain RT (<30 Gy, Group 2, n = 9) and high-dose whole-brain RT (>30 Gy, Group 3, n = 7) in addition to focal boost. Magnetic resonance images (MRIs) were analyzed at baseline and follow-up (median 14 months). The CCVs were manually segmented on midline sagittal slice (n = 23), while WBVs were segmented semi-automatically using Freesurfer (n = 15). This was done twice (6-month interval) for all baseline CCV measurements and 5 randomly selected WBV measurements to establish measurement reproducibility. Correlations between CCV and WBV were investigated and percentage of children demonstrating reduction in CCV or WBV noted. RESULTS: Correlation between baseline CCV and WBV was not significant (p = 0.37). Measurement reproducibility was from 6% to -9% for CCV and from 4.8% to -1.2% for WBV. Among the children studied, 30.4% (7/23) had >9% reduction in CCV at follow-up, while 33.3% (5/15) had >1.2% reduction in WBV. Five of 7 patients with CCV loss were not picked up by WBV measurements. Similarly, 3 of 5 patients with WBV loss were not picked up by CCV measurements. CONCLUSIONS: The CCV and the WBV are unrelated and may indicate different brain parenchymal losses following RT. Up to a third of posterior fossa tumors treated with RT have measurable CCV or WBV loss; incidence was equivalent in lowvs high-dose whole-brain RT.


Assuntos
Neoplasias Encefálicas/radioterapia , Encéfalo/efeitos da radiação , Corpo Caloso/efeitos da radiação , Neoplasias Infratentoriais/radioterapia , Radioterapia/efeitos adversos , Criança , Humanos , Tamanho do Órgão/efeitos da radiação , Reprodutibilidade dos Testes
3.
Int J Radiat Oncol Biol Phys ; 101(5): 1234-1242, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29908790

RESUMO

PURPOSE: Brain radiation is associated with functional deficits in children. The purpose of this study was to examine white matter integrity as measured by diffusion tensor imaging and associations with region-specific radiation dose and neuropsychological functioning in children treated with cranial irradiation. METHODS AND MATERIALS: A total of 20 patients and 55 age- and sex-matched controls were included in the present study. Diffusion tensor imaging and neuropsychological assessments were conducted at baseline and 6, 15, and 27 months after treatment. The neuropsychological assessment included motor dexterity, working memory, and processing speed. White matter regions were contoured, and the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were recorded for each participant. Linear mixed effects regression models were used to prospectively compare the associations among ADC, FA, radiation dose to contoured structures, and performance on the neuropsychological assessments over time. RESULTS: The mean prescription dose was 44 Gy (range 12-54). Across visits, compared with the controls, the patients showed a significantly increased ADC across all selected regions and alterations in FA in the dorsal midbrain and corpus callosum (genu, splenium, body). An increased radiation dose to the genu and body of the corpus callosum was associated with alterations in ADC and FA and reduced neuropsychological performance, most notably motor speed and processing. CONCLUSIONS: These prospective data suggest that subcortical white matter, especially the genu and body of the corpus callosum, could be regions with increased susceptibility to radiation-induced injury, with implications for cognitive function.


Assuntos
Encéfalo/efeitos da radiação , Cognição/efeitos da radiação , Corpo Caloso/efeitos da radiação , Neurônios/efeitos da radiação , Adolescente , Anisotropia , Comportamento , Encéfalo/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Estudos de Casos e Controles , Criança , Pré-Escolar , Corpo Caloso/patologia , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Neurônios/patologia , Testes Neuropsicológicos , Estudos Prospectivos , Substância Branca/diagnóstico por imagem , Substância Branca/efeitos da radiação
4.
Radiat Res ; 188(4): 443-454, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28777696

RESUMO

Cranial radiation severely affects brain health and function, including glial cell production and myelination. Recent studies indicate that voluntary exercise has beneficial effects on oligodendrogenesis and myelination. Here, we hypothesized that voluntary running would increase oligodendrocyte numbers in the corpus callosum after irradiation of the juvenile mouse brain. The brains of C57Bl/6J male mice were 6 Gy irradiated on postnatal day 9 during the main gliogenic developmental phase, resulting in a loss of oligodendrocyte precursor cells. Upon adulthood, the mice were injected with bromodeoxyuridine and allowed to exercise on a running wheel for four weeks. Cell proliferation and survival, Ascl1+ oligodendrocyte precursor and Olig2+ oligodendrocyte cell numbers as well as CC1+ mature oligodendrocytes were quantified using immunohistology. Radiation induced a reduction in the number of Olig2+ oligodendrocytes by nearly 50% without affecting production or survival of new Olig2+ cells. Ascl1+ cells earlier in the oligodendroglial cell lineage were also profoundly affected, with numbers reduced by half. By three weeks of age, Olig2+ cell numbers had not recovered, and this was paralleled by a volumetric loss in the corpus callosum. The deficiency of Olig2+ oligodendrocytes persisted into adulthood. Additionally, the depletion of Ascl1+ progenitor cells was irreversible, and was even more pronounced at 12 weeks postirradiation compared to day 2 postirradiation. Furthermore, the overall number of CC1+ mature oligodendrocytes decreased by 28%. The depletion of Olig2+ cells in irradiated animals was reversed by 4 weeks of voluntary exercise. Moreover, voluntary exercise also increased the number of Ascl1+ progenitor cells in irradiated animals. Taken together, these results demonstrate that exercise in adulthood significantly ameliorates the profound and long-lasting effects of moderate exposure to immature oligodendrocytes during postnatal development.


Assuntos
Encéfalo/citologia , Encéfalo/efeitos da radiação , Oligodendroglia/citologia , Condicionamento Físico Animal/fisiologia , Animais , Contagem de Células , Proliferação de Células/efeitos da radiação , Corpo Caloso/citologia , Corpo Caloso/efeitos da radiação , Relação Dose-Resposta à Radiação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Neurais/citologia , Tamanho do Órgão/efeitos da radiação , Fatores de Tempo , Substância Branca/citologia , Substância Branca/efeitos da radiação
5.
Pediatr Radiol ; 47(13): 1809-1816, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28844078

RESUMO

BACKGROUND: Despite improving survival rates, children are at risk for long-term cognitive and behavioral difficulties following the diagnosis and treatment of a brain tumor. Surgery, chemotherapy and radiation therapy have all been shown to impact the developing brain, especially the white matter. OBJECTIVE: The purpose of this study was to determine the long-term effects of radiation therapy on white matter integrity, as measured by diffusion tensor imaging, in pediatric brain tumor patients 2 years after the end of radiation treatment, while controlling for surgical interventions. MATERIALS AND METHODS: We evaluated diffusion tensor imaging performed at two time points: a baseline 3 to 12 months after surgery and a follow-up approximately 2 years later in pediatric brain tumor patients. A region of interest analysis was performed within three regions of the corpus callosum. Diffusion tensor metrics were determined for participants (n=22) who underwent surgical tumor resection and radiation therapy and demographically matched with participants (n=22) who received surgical tumor resection only. RESULTS: Analysis revealed that 2 years after treatment, the radiation treated group exhibited significantly lower fractional anisotropy and significantly higher radial diffusivity within the body of the corpus callosum compared to the group that did not receive radiation. CONCLUSION: The findings indicate that pediatric brain tumor patients treated with radiation therapy may be at greater risk of experiencing long-term damage to the body of the corpus callosum than those treated with surgery alone.


Assuntos
Neoplasias Encefálicas/radioterapia , Corpo Caloso/efeitos da radiação , Imagem de Tensor de Difusão/métodos , Substância Branca/efeitos da radiação , Anisotropia , Criança , Corpo Caloso/patologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Substância Branca/patologia
7.
Int J Radiat Oncol Biol Phys ; 96(2): 470-478, 2016 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-27478168

RESUMO

PURPOSE: In pediatric cancer survivors treated with whole-brain irradiation (WBI), long-term cognitive deficits and morbidity develop that are poorly understood and for which there is no treatment. We describe similar cognitive defects in juvenile WBI rats and correlate them with alterations in diffusion tensor imaging and magnetic resonance spectroscopy (MRS) during brain development. METHODS AND MATERIALS: Juvenile Fischer rats received clinically relevant fractionated doses of WBI or a high-dose exposure. Diffusion tensor imaging and MRS were performed at the time of WBI and during the subacute (3-month) and late (6-month) phases, before behavioral testing. RESULTS: Fractional anisotropy in the splenium of the corpus callosum increased steadily over the study period, reflecting brain development. WBI did not alter the subacute response, but thereafter there was no further increase in fractional anisotropy, especially in the high-dose group. Similarly, the ratios of various MRS metabolites to creatine increased over the study period, and in general, the most significant changes after WBI were during the late phase and with the higher dose. The most dramatic changes observed were in glutamine-creatine ratios that failed to increase normally between 3 and 6 months after either radiation dose. WBI did not affect the ambulatory response to novel open field testing in the subacute phase, but locomotor habituation was impaired and anxiety-like behaviors increased. As for cognitive measures, the most dramatic impairments were in novel object recognition late after either dose of WBI. CONCLUSIONS: The developing brains of juvenile rats given clinically relevant fractionated doses of WBI show few abnormalities in the subacute phase but marked late cognitive alterations that may be linked with perturbed MRS signals measured in the corpus callosum. This pathomimetic phenotype of clinically relevant cranial irradiation effects may be useful for modeling, mechanistic evaluations, and testing of mitigation approaches.


Assuntos
Transtornos Cognitivos/patologia , Transtornos Cognitivos/fisiopatologia , Corpo Caloso/patologia , Corpo Caloso/fisiopatologia , Irradiação Craniana/efeitos adversos , Imagem de Tensor de Difusão/métodos , Animais , Transtornos Cognitivos/etiologia , Corpo Caloso/efeitos da radiação , Relação Dose-Resposta à Radiação , Masculino , Doses de Radiação , Ratos , Ratos Endogâmicos F344
8.
Int J Radiat Oncol Biol Phys ; 93(1): 64-71, 2015 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-26279025

RESUMO

PURPOSE: The purpose of this study was to determine radiation dose effect on the structural integrity of cerebral white matter in craniopharyngioma patients receiving surgery and proton therapy. METHODS AND MATERIALS: Fifty-one patients (2.1-19.3 years of age) with craniopharyngioma underwent surgery and proton therapy in a prospective therapeutic trial. Anatomical magnetic resonance images acquired after surgery but before proton therapy were inspected to identify white matter structures intersected by surgical corridors and catheter tracks. Longitudinal diffusion tensor imaging (DTI) was performed to measure microstructural integrity changes in cerebral white matter. Fractional anisotropy (FA) derived from DTI was statistically analyzed for 51 atlas-based white matter structures of the brain to determine radiation dose effect. FA in surgery-affected regions in the corpus callosum was compared to that in its intact counterpart to determine whether surgical defects affect radiation dose effect. RESULTS: Surgical defects were seen most frequently in the corpus callosum because of transcallosal resection of tumors and insertion of ventricular or cyst catheters. Longitudinal DTI data indicated reductions in FA 3 months after therapy, which was followed by a recovery in most white matter structures. A greater FA reduction was correlated with a higher radiation dose in 20 white matter structures, indicating a radiation dose effect. The average FA in the surgery-affected regions before proton therapy was smaller (P=.0001) than that in their non-surgery-affected counterparts with more intensified subsequent reduction of FA (P=.0083) after therapy, suggesting that surgery accentuated the radiation dose effect. CONCLUSIONS: DTI data suggest that mild radiation dose effects occur in patients with craniopharyngioma receiving surgery and proton therapy. Surgical defects present at the time of proton therapy appear to accentuate the radiation dose effect longitudinally. This study supports consideration of pre-existing surgical defects and their locations in proton therapy planning and studies of treatment effect.


Assuntos
Craniofaringioma/radioterapia , Craniofaringioma/cirurgia , Neoplasias Hipofisárias/radioterapia , Neoplasias Hipofisárias/cirurgia , Terapia com Prótons , Substância Branca/efeitos da radiação , Substância Branca/cirurgia , Adolescente , Criança , Pré-Escolar , Corpo Caloso/efeitos da radiação , Corpo Caloso/cirurgia , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Doses de Radiação , Adulto Jovem
9.
Mol Cancer Ther ; 14(1): 70-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25319393

RESUMO

Cranial irradiation is a standard therapy for primary and metastatic brain tumors. A major drawback of radiotherapy (RT), however, is long-term cognitive loss that affects quality of life. Radiation-induced oxidative stress in normal brain tissue is thought to contribute to cognitive decline. We evaluated the effectiveness of a novel mimic of superoxide dismutase enzyme (SOD), MnTnBuOE-2-PyP(5+)(Mn(III) meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin), to provide long-term neuroprotection following 8 Gy of whole brain irradiation. Long-term RT damage can only be assessed by brain imaging and neurocognitive studies. C57BL/6J mice were treated with MnTnBuOE-2-PyP(5+) before and after RT and evaluated three months later. At this time point, drug concentration in the brain was 25 nmol/L. Mice treated with MnTnBuOE-2-PyP(5+)/RT exhibited MRI evidence for myelin preservation in the corpus callosum compared with saline/RT treatment. Corpus callosum histology demonstrated a significant loss of axons in the saline/RT group that was rescued in the MnTnBuOE-2-PyP(5+)/RT group. In addition, the saline/RT groups exhibited deficits in motor proficiency as assessed by the rotorod test and running wheel tests. These deficits were ameliorated in groups treated with MnTnBuOE-2-PyP(5+)/RT. Our data demonstrate that MnTnBuOE-2-PyP(5+) is neuroprotective for oxidative stress damage caused by radiation exposure. In addition, glioblastoma cells were not protected by MnTnBuOE-2-PyP(5+) combination with radiation in vitro. Likewise, the combination of MnTnBuOE-2-PyP(5+) with radiation inhibited tumor growth more than RT alone in flank tumors. In summary, MnTnBuOE-2-PyP(5+) has dual activity as a neuroprotector and a tumor radiosensitizer. Thus, it is an attractive candidate for adjuvant therapy with RT in future studies with patients with brain cancer.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Metaloporfirinas/administração & dosagem , Atividade Motora/efeitos da radiação , Protetores contra Radiação/administração & dosagem , Substância Branca/efeitos da radiação , Animais , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Linhagem Celular Tumoral , Corpo Caloso/efeitos da radiação , Glioblastoma/patologia , Glioblastoma/radioterapia , Humanos , Metaloporfirinas/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Protetores contra Radiação/farmacologia , Substância Branca/patologia
10.
Phys Med Biol ; 59(10): 2535-47, 2014 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-24778364

RESUMO

Radiation necrosis is an uncommon but severe adverse effect of brain radiation therapy (RT). Current predictive models based on radiation dose have limited accuracy. We aimed to identify early individual response biomarkers based upon diffusion tensor (DT) imaging and incorporated them into a response model for prediction of radiation necrosis. Twenty-nine patients with glioblastoma received six weeks of intensity modulated RT and concurrent temozolomide. Patients underwent DT-MRI scans before treatment, at three weeks during RT, and one, three, and six months after RT. Cases with radiation necrosis were classified based on generalized equivalent uniform dose (gEUD) of whole brain and DT index early changes in the corpus callosum and its substructures. Significant covariates were used to develop normal tissue complication probability models using binary logistic regression. Seven patients developed radiation necrosis. Percentage changes of radial diffusivity (RD) in the splenium at three weeks during RT and at six months after RT differed significantly between the patients with and without necrosis (p = 0.05 and p = 0.01). Percentage change of RD at three weeks during RT in the 30 Gy dose-volume of the splenium and brain gEUD combined yielded the best-fit logistic regression model. Our findings indicate that early individual response during the course of RT, assessed by radial diffusivity, has the potential to aid the prediction of delayed radiation necrosis, which could provide guidance in dose-escalation trials.


Assuntos
Encéfalo/patologia , Encéfalo/efeitos da radiação , Imagem de Tensor de Difusão , Lesões por Radiação/etiologia , Adulto , Idoso , Biomarcadores/metabolismo , Corpo Caloso/patologia , Corpo Caloso/efeitos da radiação , Relação Dose-Resposta à Radiação , Feminino , Glioma/patologia , Glioma/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Análise Multivariada , Necrose/etiologia , Resultado do Tratamento , Substância Branca/patologia , Substância Branca/efeitos da radiação , Adulto Jovem
11.
PLoS One ; 8(3): e57768, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23469234

RESUMO

PURPOSE: There is little known about how brain white matter structures differ in their response to radiation, which may have implications for radiation-induced neurocognitive impairment. We used diffusion tensor imaging (DTI) to examine regional variation in white matter changes following chemoradiotherapy. METHODS: Fourteen patients receiving two or three weeks of whole-brain radiation therapy (RT) ± chemotherapy underwent DTI pre-RT, at end-RT, and one month post-RT. Three diffusion indices were measured: fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). We determined significant individual voxel changes of diffusion indices using tract-based spatial statistics, and mean changes of the indices within fourteen white matter structures of interest. RESULTS: Voxels of significant FA decreases and RD increases were seen in all structures (p<0.05), with the largest changes (20-50%) in the fornix, cingula, and corpus callosum. There were highly significant between-structure differences in pre-RT to end-RT mean FA changes (p<0.001). The inferior cingula had a mean FA decrease from pre-RT to end-RT significantly greater than 11 of the 13 other structures (p<0.00385). CONCLUSIONS: Brain white matter structures varied greatly in their response to chemoradiotherapy as measured by DTI changes. Changes in FA and RD related to white matter demyelination were prominent in the cingula and fornix, structures relevant to radiation-induced neurocognitive impairment. Future research should evaluate DTI as a predictive biomarker of brain chemoradiotherapy adverse effects.


Assuntos
Neoplasias Encefálicas/patologia , Corpo Caloso/patologia , Fórnice/patologia , Giro do Cíngulo/patologia , Melanoma/patologia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/terapia , Quimiorradioterapia , Cognição/efeitos dos fármacos , Cognição/efeitos da radiação , Corpo Caloso/efeitos dos fármacos , Corpo Caloso/efeitos da radiação , Doenças Desmielinizantes , Imagem de Tensor de Difusão , Feminino , Fórnice/efeitos dos fármacos , Fórnice/efeitos da radiação , Raios gama , Giro do Cíngulo/efeitos dos fármacos , Giro do Cíngulo/efeitos da radiação , Humanos , Masculino , Melanoma/terapia , Pessoa de Meia-Idade , Fibras Nervosas Mielinizadas/efeitos dos fármacos , Fibras Nervosas Mielinizadas/patologia , Fibras Nervosas Mielinizadas/efeitos da radiação , Estudos Prospectivos
12.
J Mol Neurosci ; 48(1): 144-53, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22588976

RESUMO

Electromagnetic fields (EMFs) may affect the endogenous neural stem cells within the brain. The aim of this study was to assess the effects of EMFs on the process of toxin-induced demyelination and subsequent remyelination. Demyelination was induced using local injection of lysophosphatidylcholine within the corpus callosum of adult female Sprague-Dawley rats. EMFs (60 Hz; 0.7 mT) were applied for 2 h twice a day for 7, 14, or 28 days postlesion. BrdU labeling and immunostaining against nestin, myelin basic protein (MBP), and BrdU were used for assessing the amount of neural stem cells within the tissue, remyelination patterns, and tracing of proliferating cells, respectively. EMFs significantly reduced the extent of demyelinated area and increased the level of MBP staining within the lesion area on days 14 and 28 postlesion. EMFs also increased the number of BrdU- and nestin-positive cells within the area between SVZ and lesion as observed on days 7 and 14 postlesion. It seems that EMF potentiates proliferation and migration of neural stem cells and enhances the repair of myelin in the context of demyelinating conditions.


Assuntos
Terapia por Estimulação Elétrica/métodos , Degeneração Neural/terapia , Regeneração Nervosa/efeitos da radiação , Células-Tronco Neurais/efeitos da radiação , Estimulação Magnética Transcraniana/métodos , Animais , Bromodesoxiuridina/metabolismo , Movimento Celular/fisiologia , Movimento Celular/efeitos da radiação , Proliferação de Células/efeitos da radiação , Corpo Caloso/fisiologia , Corpo Caloso/efeitos da radiação , Modelos Animais de Doenças , Feminino , Proteínas de Filamentos Intermediários/metabolismo , Esclerose Múltipla/fisiopatologia , Esclerose Múltipla/terapia , Proteína Básica da Mielina/metabolismo , Bainha de Mielina/metabolismo , Bainha de Mielina/efeitos da radiação , Degeneração Neural/fisiopatologia , Regeneração Nervosa/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Nestina , Células-Tronco Neurais/citologia , Ratos , Ratos Sprague-Dawley , Nicho de Células-Tronco/fisiologia
14.
Fetal Pediatr Pathol ; 27(6): 264-73, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19065324

RESUMO

Agenesis of the corpus callosum is found in about 5 per 1,000 births and it is due to maldevelopment or, secondary, to destructive lesions. Multicystic dysplastic kidneys is a consequence of either developmental failure of the mesonephric blastema to form nephrons or to early urinary obstruction due to urethral or ureteric atresia and can be found in about 1 per 1,000 live births. A case of fetal multicystic dysplastic kidney disease (Potter type II syndrome) and complete agenesis of the corpus callosum demonstrated by the presence of Probst bundles associated with colpocephaly occurring in the same mother in her two consecutive pregnancies is reported. Data regarding possible teratogenetic effect due to electromagnetic exposure in utero have also been investigated and raised suspicionus as a potential risk factor. In cases of suspected second trimester ultrasound diagnosis of agenesis of corpus callosum (ACC), the following clinical management should be recommended: fetal karyotype; a second level scan with differentiation between underlying conditions such as hydrocephalus and holoprosencephaly; antenatal MRI to enhance the diagnostic accuracy of possible associated neuronal migration (when possible); and direct demonstration of the presence of the Probst bundles to neurohistology.


Assuntos
Anormalidades Múltiplas , Corpo Caloso , Rim Displásico Multicístico , Radiação , Teratogênicos , Anormalidades Múltiplas/etiologia , Anormalidades Múltiplas/patologia , Adulto , Agenesia do Corpo Caloso , Corpo Caloso/efeitos da radiação , Feminino , Humanos , Exposição Materna , Rim Displásico Multicístico/etiologia , Rim Displásico Multicístico/patologia , Gravidez , Diagnóstico Pré-Natal
15.
PLoS One ; 2(7): e588, 2007 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-17622341

RESUMO

BACKGROUND: The cellular basis of long term radiation damage in the brain is not fully understood. METHODS AND FINDINGS: We administered a dose of 25Gy to adult rat brains while shielding the olfactory bulbs. Quantitative analyses were serially performed on different brain regions over 15 months. Our data reveal an immediate and permanent suppression of SVZ proliferation and neurogenesis. The olfactory bulb demonstrates a transient but remarkable SVZ-independent ability for compensation and maintenance of the calretinin interneuron population. The oligodendrocyte compartment exhibits a complex pattern of limited proliferation of NG2 progenitors but steady loss of the oligodendroglial antigen O4. As of nine months post radiation, diffuse demyelination starts in all irradiated brains. Counts of capillary segments and length demonstrate significant loss one day post radiation but swift and persistent recovery of the vasculature up to 15 months post XRT. MRI imaging confirms loss of volume of the corpus callosum and early signs of demyelination at 12 months. Ultrastructural analysis demonstrates progressive degradation of myelin sheaths with axonal preservation. Areas of focal necrosis appear beyond 15 months and are preceded by widespread demyelination. Human white matter specimens obtained post-radiation confirm early loss of oligodendrocyte progenitors and delayed onset of myelin sheath fragmentation with preserved capillaries. CONCLUSIONS: This study demonstrates that long term radiation injury is associated with irreversible damage to the neural stem cell compartment in the rodent SVZ and loss of oligodendrocyte precursor cells in both rodent and human brain. Delayed onset demyelination precedes focal necrosis and is likely due to the loss of oligodendrocyte precursors and the inability of the stem cell compartment to compensate for this loss.


Assuntos
Encéfalo/efeitos da radiação , Oligodendroglia/efeitos da radiação , Células-Tronco/efeitos da radiação , Animais , Calbindina 2 , Divisão Celular/efeitos da radiação , Córtex Cerebral/efeitos da radiação , Ventrículos Cerebrais/fisiologia , Ventrículos Cerebrais/efeitos da radiação , Corpo Caloso/anatomia & histologia , Corpo Caloso/efeitos da radiação , Feminino , Humanos , Interneurônios/fisiologia , Interneurônios/efeitos da radiação , Imageamento por Ressonância Magnética , Bainha de Mielina/patologia , Bainha de Mielina/efeitos da radiação , Necrose , Bulbo Olfatório/patologia , Bulbo Olfatório/efeitos da radiação , Radioterapia/efeitos adversos , Radioterapia/métodos , Ratos , Ratos Sprague-Dawley , Proteína G de Ligação ao Cálcio S100/metabolismo , Proteína G de Ligação ao Cálcio S100/efeitos da radiação
16.
Brain Res ; 1154: 225-36, 2007 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-17481596

RESUMO

Prior investigations of traumatic axonal injury (TAI), and pharmacological treatments of TAI pathology, have focused exclusively on the role of myelinated axons, with no systematic observations directed towards unmyelinated axon pathophysiology. Recent electrophysiological evidence, however, indicates that unmyelinated axons are more vulnerable than myelinated axons in a rodent model of experimental TAI. Given their susceptibility to TAI, the present study examines whether unmyelinated axons also respond differentially to FK506, an immunophilin ligand with well-established neuroprotective efficacy in the myelinated fiber population. Adult rats received 3.0 mg/kg FK506 intravenously at 30 min prior to midline fluid percussion injury. In brain slice electrophysiological recordings, conducted at 24 h postinjury, compound action potentials (CAPs) were evoked in the corpus callosum, and injury effects quantified separately for CAP waveform components generated by myelinated axons (N1 wave) and unmyelinated axons (N2 wave). The amplitudes of both CAP components were suppressed postinjury, although this deficit was 16% greater for the N2 CAP. While FK506 treatment provided significant neuroprotection for both N1 and N2 CAPs, the drug benefit for the N2 CAP amplitude was 122% greater than that for the N1 CAPs, and improved postinjury strength-duration and refractoriness properties only in N2 CAPs. Immunocytochemical observations, of TAI reflected in intra-axonal pooling of amyloid precursor protein, indicated that FK506 reduced the extent of postinjury impairments to axonal transport and subsequent axonal damage. Collectively, these studies further substantiate a distinctive role of unmyelinated axons in TAI, and suggest a highly efficacious neuroprotective strategy to target this axonal population.


Assuntos
Axônios/efeitos dos fármacos , Lesões Encefálicas/patologia , Lesões Encefálicas/prevenção & controle , Fibras Nervosas Amielínicas/patologia , Fármacos Neuroprotetores/uso terapêutico , Tacrolimo/uso terapêutico , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Axônios/fisiologia , Lesões Encefálicas/complicações , Corpo Caloso/fisiopatologia , Corpo Caloso/efeitos da radiação , Modelos Animais de Doenças , Relação Dose-Resposta à Radiação , Estimulação Elétrica/métodos , Potenciais Evocados/fisiologia , Potenciais Evocados/efeitos da radiação , Técnicas In Vitro , Masculino , Análise Multivariada , Fibras Nervosas Amielínicas/efeitos dos fármacos , Fibras Nervosas Amielínicas/fisiologia , Ratos , Ratos Sprague-Dawley
17.
Eur J Neurol ; 13(7): 749-53, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16834705

RESUMO

A case of Marchiafava-Bignami (MB) syndrome with selective callosal involvement was evaluated by clinical examination and magnetic resonance imaging (MRI) in the acute phase and 6 months after the onset of symptoms; at the same time, the corticospinally and transcallosally mediated effects elicited by transcranial magnetic stimulation (TMS) were investigated. The first MRI study showed the presence of extensive abnormal signal intensity throughout the entire corpus callosum. After high-dose corticosteroid administration her symptoms rapidly resolved, in parallel with the reversion of MRI changes, except for severe cognitive impairment. Follow-up TMS examination revealed persistent transcallosal inhibition (TI) abnormalities. This report indicates that the measurement of TI during the course of MB syndrome is useful for evaluating functional changes to the corpus callosum, including their evaluation with time and after treatment and for elucidating the pathophysiology of MB syndrome.


Assuntos
Corpo Caloso/patologia , Doenças Desmielinizantes/terapia , Transtornos Neurocognitivos/terapia , Estimulação Magnética Transcraniana/métodos , Alcoolismo/complicações , Corpo Caloso/efeitos dos fármacos , Corpo Caloso/efeitos da radiação , Doenças Desmielinizantes/etiologia , Doenças Desmielinizantes/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Eletromiografia/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Transtornos Neurocognitivos/etiologia , Tomografia Computadorizada por Raios X/métodos , Complexo Vitamínico B/administração & dosagem
18.
Clin Neurophysiol ; 117(1): 26-32, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16337187

RESUMO

OBJECTIVE: To determine if there are steroid-dependent changes in transcallosal transfer during the menstrual cycle in normal women. METHODS: We tested 13 normally cycling women during the menstrual, follicular and midluteal phases. Blood levels of estradiol (E) and progesterone (P) were determined by radioimmunoassay. Ipsilateral tonic voluntary muscle activity suppression, called ipsilateral silent period (iSP), was evoked by applying transcranial magnetic stimulation (TMS) over the left motor cortex and by measuring the EMG of the ipsilateral first dorsal interosseus (FDI) muscle. Both iSP-duration and transcallosal conduction times were measured and related to cycle phase and steroid levels. RESULTS: Duration of iSPs varied over the cycle with largest differences between follicular and midluteal phases. During the midluteal phase high levels of P were significantly related to short iSPs. This relation also applied to E levels and iSPs during the follicular phase. CONCLUSIONS: Our study shows for the first time that the transcallosal transfer is modulated by E and P and changes over the menstrual cycle. SIGNIFICANCE: It is suggested that gonadal steroid hormones affect the interhemispheric interaction and change the functional cerebral organization sex dependently via its neuromodulatory properties on GABAergic and glutamatergic neurons.


Assuntos
Corpo Caloso/efeitos da radiação , Inibição Psicológica , Ciclo Menstrual/efeitos da radiação , Córtex Motor/efeitos da radiação , Estimulação Magnética Transcraniana , Adulto , Análise de Variância , Corpo Caloso/fisiologia , Eletromiografia/métodos , Estradiol/sangue , Feminino , Lateralidade Funcional/fisiologia , Humanos , Modelos Lineares , Ciclo Menstrual/sangue , Córtex Motor/fisiologia , Músculo Esquelético/fisiologia , Músculo Esquelético/efeitos da radiação , Progesterona/sangue , Radioimunoensaio/métodos , Fatores de Tempo
19.
Neurology ; 65(6): 947-9, 2005 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-16186544

RESUMO

A 13-year-old girl with Ki-1 anaplastic large cell lymphoma (Ki-1ALCL) bulky deposits in the brain developed raised intracranial pressure and coma associated with asynchronous burst-suppression following standard dose cranial irradiation. Supportive care, steroids, and chemotherapy resulted in clinical improvement. Burst-suppression coma may be reversible when secondary to tumor, decrease in steroids, or radiation effects; the asynchrony localizes the lesion to cortical interconnections such as the corpus callosum.


Assuntos
Neoplasias Encefálicas/complicações , Coma/tratamento farmacológico , Coma/etiologia , Linfoma Anaplásico de Células Grandes/complicações , Radioterapia/efeitos adversos , Síndrome de Abstinência a Substâncias/complicações , Adolescente , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Coma/fisiopatologia , Corpo Caloso/efeitos dos fármacos , Corpo Caloso/patologia , Corpo Caloso/efeitos da radiação , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Evolução Fatal , Feminino , Humanos , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/fisiopatologia , Doenças Linfáticas/complicações , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Linfoma Anaplásico de Células Grandes/patologia , Imageamento por Ressonância Magnética , Inibição Neural/efeitos dos fármacos , Inibição Neural/efeitos da radiação , Esplenomegalia/complicações , Síndrome de Abstinência a Substâncias/etiologia , Síndrome de Abstinência a Substâncias/fisiopatologia , Resultado do Tratamento
20.
Neurol Res ; 27(4): 346-50, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15949230

RESUMO

OBJECTIVES: The present study characterized glial cell injury provoked in adult rat chiasm within 24 hours after a single, high-dose irradiation of 20 Gy. METHODS: All chiasmal glial cells in a section were counted, and the percentage of TUNEL-positive glial cells exhibiting apoptotic morphology was defined as the apoptotic rate. RESULTS: Numbers of apoptotic cells increased significantly (p<0.0001) from 3 to 8 hours after exposure, but returned to baseline levels by 24 hours. Little evidence of apoptosis was observed in non-irradiated chiasms. Similar patterns of increase in apoptotic rate were observed in the genu of the corpus callosum, but the extent was significantly lower (p=0.047) in the optic chiasm, with a maximal rate of 1.9%. Immunohistochemically, apoptotic cells were positive for CNP, a marker for oligodendrocytes. DISCUSSION: These data indicate that chiasmal irradiation induces limited, but significant apoptotic depletion of the oligodendroglial population, and may participate in the development of radiation-induced optic neuropathy.


Assuntos
Apoptose/efeitos da radiação , Oligodendroglia/efeitos da radiação , Quiasma Óptico/citologia , Lesões Experimentais por Radiação/patologia , Radiação , Análise de Variância , Animais , Contagem de Células , Corpo Caloso/efeitos da radiação , Relação Dose-Resposta à Radiação , Imuno-Histoquímica/métodos , Marcação In Situ das Extremidades Cortadas , Masculino , Nucleosídeo-Trifosfatase/metabolismo , Oligodendroglia/citologia , Quiasma Óptico/efeitos da radiação , Lesões Experimentais por Radiação/metabolismo , Ratos , Ratos Wistar , Fatores de Tempo
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