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1.
Int J Mol Sci ; 22(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066560

RESUMO

In recent decades, researchers around the world have been studying intensively how micro-organisms that are present inside living organisms could affect the main processes of life, namely health and pathological conditions of mind or body. They discovered a relationship between the whole microbial colonization and the initiation and development of different medical disorders. Besides already known probiotics, novel products such as postbiotics and paraprobiotics have been developed in recent years to create new non-viable micro-organisms or bacterial-free extracts, which can provide benefits to the host with additional bioactivity to probiotics, but without the risk of side effects. The best alternatives in the use of probiotics and postbiotics to maintain the health of the intestinal microbiota and to prevent the attachment of pathogens to children and adults are highlighted and discussed as controversies and challenges. Updated knowledge of the molecular and cellular mechanisms involved in the balance between microbiota and immune system for the introspection on the gut-lung-brain axis could reveal the latest benefits and perspectives of applied photobiomics for health. Multiple interconditioning between photobiomodulation (PBM), probiotics, and the human microbiota, their effects on the human body, and their implications for the management of viral infectious diseases is essential. Coupled complex PBM and probiotic interventions can control the microbiome, improve the activity of the immune system, and save the lives of people with immune imbalances. There is an urgent need to seek and develop innovative treatments to successfully interact with the microbiota and the human immune system in the coronavirus crisis. In the near future, photobiomics and metabolomics should be applied innovatively in the SARS-CoV-2 crisis (to study and design new therapies for COVID-19 immediately), to discover how bacteria can help us through adequate energy biostimulation to combat this pandemic, so that we can find the key to the hidden code of communication between RNA viruses, bacteria, and our body.


Assuntos
COVID-19/imunologia , COVID-19/microbiologia , Microbioma Gastrointestinal/imunologia , Terapia com Luz de Baixa Intensidade/métodos , Probióticos/uso terapêutico , SARS-CoV-2/imunologia , Encéfalo/imunologia , Encéfalo/efeitos da radiação , COVID-19/radioterapia , COVID-19/terapia , Síndrome da Liberação de Citocina/microbiologia , Síndrome da Liberação de Citocina/radioterapia , Microbioma Gastrointestinal/efeitos da radiação , Humanos , Pulmão/imunologia , Pulmão/efeitos da radiação , Metabolômica , Fototerapia/métodos , SARS-CoV-2/efeitos da radiação
2.
Nat Commun ; 12(1): 2519, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947867

RESUMO

Transcranial focused ultrasound (tFUS) is a promising neuromodulation technique, but its mechanisms remain unclear. We hypothesize that if tFUS parameters exhibit distinct modulation effects in different neuron populations, then the mechanism can be understood through identifying unique features in these neuron populations. In this work, we investigate the effect of tFUS stimulation on different functional neuron types in in vivo anesthetized rodent brains. Single neuron recordings were separated into regular-spiking and fast-spiking units based on their extracellular spike shapes acquired through intracranial electrophysiological recordings, and further validated in transgenic optogenetic mice models of light-excitable excitatory and inhibitory neurons. We show that excitatory and inhibitory neurons are intrinsically different in response to ultrasound pulse repetition frequency (PRF). The results suggest that we can preferentially target specific neuron types noninvasively by tuning the tFUS PRF. Chemically deafened rats and genetically deafened mice were further tested for validating the directly local neural effects induced by tFUS without potential auditory confounds.


Assuntos
Mapeamento Encefálico/métodos , Encéfalo/citologia , Encéfalo/efeitos da radiação , Potenciais Somatossensoriais Evocados/fisiologia , Potenciais Somatossensoriais Evocados/efeitos da radiação , Neurônios/citologia , Ultrassonografia/métodos , Animais , Encéfalo/fisiologia , Eletrofisiologia , Masculino , Camundongos , Camundongos Transgênicos , Neurônios/fisiologia , Neurônios/efeitos da radiação , Optogenética , Ratos , Ratos Wistar
3.
Anticancer Res ; 41(3): 1445-1449, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33788736

RESUMO

BACKGROUND: Limited brain metastasis is treated definitively with stereotactic radiosurgery when surgical resection is not indicated. Although this has historically been performed in a single fraction, multi-fraction approaches such as fraction radiosurgery (FSRS) and staged radiosurgery (SSRS) have been recently examined as alternative approaches for larger lesions to permit better tumor control without increased toxicity. CASE REPORT: We present the case of a patient who developed symptomatic radionecrosis in two brain metastasis, 2.3 cm and 2.1 cm in size, which were treated with 18 Gy in one fraction, but no radionecrosis in a 3.3 cm lesion treated in two fractions of 15 Gy nor in two punctate lesions that were treated in one fraction of 20 Gy. Although she did not respond to steroids, she responded to bevacizumab symptomatically and on neuroimaging. CONCLUSION: Congruent with other recent studies, our report suggests that large brain metastasis should be considered for FSRS/SSRS.


Assuntos
Neoplasias Encefálicas/radioterapia , Encéfalo/efeitos da radiação , Fracionamento da Dose de Radiação , Radiocirurgia/métodos , Adulto , Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/uso terapêutico , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Feminino , Humanos , Necrose/radioterapia , Resultado do Tratamento
4.
Radiat Res ; 195(4): 355-365, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33544844

RESUMO

Radiation-induced brain injury (RBI) is a serious complication in patients who have received radiotherapy for head and neck tumors. Currently, there is a scarcity of information on early diagnostic and preventive methods of RBI. Accumulating evidence suggests that microRNAs are involved in the regulation of radiation injury, but the molecular biological mechanism of miRNAs in RBI is largely unknown. Therefore, in our study, microRNA sequencing was used to discover differential miRNAs in the hippocampus of RBI-modeled mice, which suggested that miR-741-3p was most significantly upregulated. To clarify the underlying mechanism of miR-741-3p in RBI-modeled mice, an inhibitor of miR-741-3p (antagomiR-741) was delivered into the brain via the nasal passage before irradiation. The delivery of antagomiR-741 significantly reduced miR-741-3p levels in the hippocampus of RBI-modeled mice, and the cognitive dysfunction and neuronal apoptosis induced by radiation were also alleviated at 6 weeks postirradiation. Downregulation of miR-741-3p was found to improve the protrusion and branching status of microglia after irradiation and reduced the number of GFAP-positive astrocytes. Additionally, antagomiR-741 suppressed the radiation-induced production of pro-inflammatory cytokines IL-6 and TNF-α in the hippocampus and S100B in the serum. Furthermore, Ddr2, PKCα and St8sia1 were revealed as target genes of miR-741-3p and as potential regulatory targets for RBI. Overall, our study provides identification and functional evaluation of miRNA in RBI and lays the foundation for improving the prevention strategy for RBI based on the delivery of miRNA via the nose-brain pathway.


Assuntos
Antagomirs/farmacologia , Lesões Encefálicas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , MicroRNAs/farmacologia , Lesões por Radiação/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/efeitos da radiação , Lesões Encefálicas/etiologia , Lesões Encefálicas/genética , Lesões Encefálicas/patologia , Modelos Animais de Doenças , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/patologia , Camundongos , MicroRNAs/genética , Lesões por Radiação/genética , Lesões por Radiação/patologia , Transdução de Sinais/efeitos dos fármacos
5.
Cancer Radiother ; 25(1): 92-102, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33390318

RESUMO

PURPOSE: In literature, there are no guidelines on how to prescribe dose in the case of radiosurgery (SRS) or stereotactic irradiation of multiple and adjacent BM. Aim of this work is to furnish practical proposals of dosimetric methods for multiple neighboring BM, and to make a literature review about the SRS treatment of multiple BM, comparing radiotherapy techniques on the basis of different dosimetric parameters. MATERIALS AND METHODS: A theoretical proposal of dosimetric approaches to prescribe dose in case of multiple contiguous BM is done. A literature review between 2010 and 2020 was performed on MEDLINE and Cochrane databases according to the PRISMA methodology, with the following keywords dose prescription, radiosurgery, multiple BM. Papers not reporting dosimetric solutions to irradiate multiple BM were excluded. RESULTS: Only one article in the literature reports a practical modality of dose prescription for multiple adjacent BM. Thus, we proposed other five practical solutions to prescribe radiation dose in case of two or more neighboring BM, describing advantages and drawbacks of each method in terms of different dosimetric parameters. The literature review about dosimetric solutions to irradiate multiple BM led to 56 titles; 14 articles met the chosen criteria and we reported their results in terms of dosimetric indexes and low doses to the normal brain tissue. CONCLUSIONS: The six dosimetric approaches here described can be used by physicians for multiple contiguous BM, depending on the clinical situation. These methods may be applied in clinical studies to better evaluate their usefulness in practice.


Assuntos
Neoplasias Encefálicas/radioterapia , Radiocirurgia/métodos , Encéfalo/patologia , Encéfalo/efeitos da radiação , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Humanos , Necrose , Lesões por Radiação/patologia , Dosagem Radioterapêutica
6.
Cancer Radiother ; 25(1): 62-71, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33414057

RESUMO

PURPOSE: Nasopharyngeal carcinoma (NPC) radiotherapy (RT) irradiates parts of the brain which may cause cerebral tissue changes. This study aimed to systematically review the brain microstructure changes using MRI-based measures, diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI) and voxel-based morphometry (VBM) and the impact of dose and latency following RT. METHODS: PubMed and Scopus databases were searched based on PRISMA guideline to determine studies focusing on changes following NPC RT. RESULTS: Eleven studies fulfilled the inclusion criteria. Microstructural changes occur most consistently in the temporal region. The changes were correlated with latency in seven studies; fractional anisotropy (FA) and gray matter (GM) volume remained low even after a longer period following RT and areas beyond irradiation site with reduced FA and GM measures. For dosage, only one study showed correlation, thus requiring further investigations. CONCLUSION: DTI, DKI and VBM may be used as a surveillance tool in detecting brain microstructural changes of NPC patients which correlates to latency and brain areas following RT.


Assuntos
Encéfalo/efeitos da radiação , Imageamento por Ressonância Magnética , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Encéfalo/diagnóstico por imagem , Encéfalo/ultraestrutura , Imagem de Tensor de Difusão , Humanos , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/efeitos da radiação , Lobo Temporal/ultraestrutura
7.
Radiat Res ; 195(3): 230-234, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33347596

RESUMO

MR-linac technology enhances the precision of therapeutic radiation by clarifying the tumor-normal tissue interface and provides the potential for adaptive treatment planning. Accurate delineation of tumors on diagnostic magnetic resonance imaging (MRI) frequently requires gadolinium-based contrast agents (GBCAs). Despite generally being considered safe, previous literature suggests that GBCAs are capable of contrast-induced acute kidney injury (AKI). It is unclear if the risk for AKI is enhanced when GBCAs are administered concurrently with ionizing radiotherapy. During irradiation, gadolinium may be liberated from its chelator which may induce AKI. The goal of this work was to determine if radiation combined with GBCAs increased the incidence of AKI. Using a preclinical MRI-guided irradiation system, where MRI acquisitions and radiation delivery are performed in rapid succession, tumor-bearing mice with normal kidney function were injected with GBCA and treated with 2, 8 or 18 Gy irradiation. Renal function was assessed on days three and seven postirradiation to assess for AKI. No clinically relevant changes in blood urea nitrogen and creatinine were observed in any combination of GBCA and radiation dose. From these data, we conclude that GBCA in combination with radiation does not increase the risk for AKI in mice. Additional investigation of multiple doses of GBCA administered concurrently with irradiation is warranted to evaluate the risk of chronic kidney injury.


Assuntos
Injúria Renal Aguda/diagnóstico por imagem , Meios de Contraste/farmacologia , Compostos Organometálicos/farmacologia , Radiação Ionizante , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/fisiopatologia , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/efeitos da radiação , Meios de Contraste/efeitos adversos , Modelos Animais de Doenças , Gadolínio/efeitos adversos , Gadolínio/farmacologia , Humanos , Rim/diagnóstico por imagem , Rim/efeitos dos fármacos , Rim/patologia , Rim/efeitos da radiação , Imageamento por Ressonância Magnética , Camundongos , Compostos Organometálicos/efeitos adversos , Radioterapia Guiada por Imagem/efeitos adversos , Radioterapia Guiada por Imagem/métodos
8.
Anticancer Res ; 40(11): 6123-6135, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109550

RESUMO

BACKGROUND/AIM: The importance of hadron therapy in the cancer management is growing. We aimed to refine the biological effect detection using a vertebrate model. MATERIALS AND METHODS: Embryos at 24 and 72 h postfertilization were irradiated at the entrance plateau and the mid spread-out Bragg peak of a 150 MeV proton beam and with reference photons. Radiation-induced DNA double-strand breaks (DSB) and histopathological changes of the eye, muscles and brain were evaluated; deterioration of specific organs (eye, yolk sac, body) was measured. RESULTS: More and longer-lasting DSBs occurred in eye and muscle cells due to proton versus photon beams, albeit in different numbers. Edema, necrosis and tissue disorganization, (especially in the eye) were observed. Dose-dependent morphological deteriorations were detected at ≥10 Gy dose levels, with relative biological effectiveness between 0.99±0.07 (length) and 1.12±0.19 (eye). CONCLUSION: Quantitative assessment of radiation induced changes in zebrafish embryos proved to be beneficial for the radiobiological characterization of proton beams.


Assuntos
Fótons , Prótons , Peixe-Zebra/fisiologia , Animais , Encéfalo/efeitos da radiação , Dano ao DNA , Modelos Animais de Doenças , Relação Dose-Resposta à Radiação , Embrião não Mamífero/efeitos da radiação , Olho/patologia , Olho/efeitos da radiação , Cinética , Tamanho do Órgão/efeitos da radiação , Eficiência Biológica Relativa , Saco Vitelino/patologia , Saco Vitelino/efeitos da radiação , Peixe-Zebra/embriologia
9.
Neuron ; 108(1): 93-110, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33058769

RESUMO

Visualizing and perturbing neural activity on a brain-wide scale in model animals and humans is a major goal of neuroscience technology development. Established electrical and optical techniques typically break down at this scale due to inherent physical limitations. In contrast, ultrasound readily permeates the brain, and in some cases the skull, and interacts with tissue with a fundamental resolution on the order of 100 µm and 1 ms. This basic ability has motivated major efforts to harness ultrasound as a modality for large-scale brain imaging and modulation. These efforts have resulted in already-useful neuroscience tools, including high-resolution hemodynamic functional imaging, focused ultrasound neuromodulation, and local drug delivery. Furthermore, recent breakthroughs promise to connect ultrasound to neurons at the genetic level for biomolecular imaging and sonogenetic control. In this article, we review the state of the art and ongoing developments in ultrasonic neurotechnology, building from fundamental principles to current utility, open questions, and future potential.


Assuntos
Encéfalo/diagnóstico por imagem , Sistemas de Liberação de Medicamentos/métodos , Ecoencefalografia/métodos , Imagem Molecular/métodos , Ondas Ultrassônicas , Animais , Barreira Hematoencefálica/efeitos da radiação , Encéfalo/fisiologia , Encéfalo/efeitos da radiação , Neuroimagem Funcional , Hemodinâmica , Humanos , Proteínas , Terapia por Ultrassom , Ultrassonografia , Ultrassonografia Doppler Transcraniana/métodos
11.
Br J Radiol ; 93(1115): 20200245, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32970457

RESUMO

Not surprisingly, our knowledge of the impact of radiation on the brain has evolved considerably. Decades of work have struggled with identifying the critical cellular targets in the brain, the latency of functional change and understanding how irradiation alters the balance between excitatory and inhibitory circuits. Radiation-induced cell kill following clinical fractionation paradigms pointed to both stromal and parenchymal targets but also defined an exquisite sensitivity of neurogenic populations of newly born cells in the brain. It became more and more apparent too, that acute (days) events transpiring after exposure were poorly prognostic of the late (months-years) waves of radiation injury believed to underlie neurocognitive deficits. Much of these gaps in knowledge persisted as NASA became interested in how exposure to much different radiation types, doses and dose rates that characterize the space radiation environment might impair central nervous system functionality, with possibly negative implications for deep space travel. Now emerging evidence from researchers engaged in clinical, translational and environmental radiation sciences have begun to fill these gaps and have uncovered some surprising similarities in the response of the brain to seemingly disparate exposure scenarios. This article highlights many of the commonalities between the vastly different irradiation paradigms that distinguish clinical treatments from occupational exposures in deep space.


Assuntos
Neoplasias Encefálicas/radioterapia , Encéfalo/efeitos da radiação , Exposição à Radiação/efeitos adversos , Lesões por Radiação/complicações , Voo Espacial , Neoplasias Encefálicas/terapia , Transtornos Cognitivos/etiologia , Humanos , Íons , Transferência Linear de Energia , Doses de Radiação , Exposição à Radiação/prevenção & controle , Lesões por Radiação/prevenção & controle
12.
Neurology ; 95(10): e1392-e1403, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32631922

RESUMO

OBJECTIVE: To develop and validate a nomogram to predict epilepsy in patients with radiation-induced brain necrosis (RN). METHODS: The nomogram was based on a retrospective analysis of 302 patients who were diagnosed with symptomatic RN from January 2005 to January 2016 in Sun Yat-sen Memorial Hospital using the Cox proportional hazards model. Discrimination of the nomogram was assessed by the concordance index (C index) and the calibration curve. The results were internally validated using bootstrap resampling and externally validated using 128 patients with RN from 2 additional hospitals. RESULTS: A total of 302 patients with RN with a median follow-up of 3.43 years (interquartile range 2.54-5.45) were included in the training cohort; 65 (21.5%) developed symptomatic epilepsy during follow-up. Seven variables remained significant predictors of epilepsy after multivariable analyses: MRI lesion volume, creatine phosphokinase, the maximum radiation dose to the temporal lobe, RN treatment, history of hypertension and/or diabetes, sex, and total cholesterol level. In the validation cohort, 28 out of 128 (21.9%) patients had epilepsy after RN within a median follow-up of 3.2 years. The nomogram showed comparable discrimination between the training and validation cohort (corrected C index 0.76 [training] vs 0.72 [95% confidence interval 0.62-0.81; validation]). CONCLUSION: Our study developed an easily applied nomogram for the prediction of RN-related epilepsy in a large RN cohort. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that a nomogram predicts post-RN epilepsy.


Assuntos
Irradiação Craniana/efeitos adversos , Epilepsia/diagnóstico , Epilepsia/etiologia , Nomogramas , Lesões por Radiação/complicações , Encéfalo/patologia , Encéfalo/efeitos da radiação , Feminino , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Necrose/etiologia , Necrose/patologia , Lesões por Radiação/diagnóstico , Lesões por Radiação/patologia , Estudos Retrospectivos , Fatores de Risco
13.
Psychopharmacology (Berl) ; 237(7): 2089-2101, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32494972

RESUMO

RATIONALE: Approximately 20-40% of patients with cancer will experience brain metastasis (BM), which has a great impact on the quality of life and survival rates of patients. Whole brain radiotherapy (WBRT) is an effective method for the treatment of BM. However, it cannot be ignored that WBRT might induce a series of neuropsychiatric side effects, including cognitive dysfunction (CD). Accumulating evidence shows that the gut microbiota and the gut-microbiota-brain axis may play a vital role in the pathogenesis of CD. OBJECTIVE AND METHODS: We adopted WBRT to mimic CD after a hierarchical cluster analysis of the Morris water maze test (MWMT) results. In addition, we observed the effects of antibiotics and prebiotics on WBRT-induced CD. Variations were revealed via the 16S rRNA sequencing analysis at different levels. RESULTS: The 16S rRNA sequencing analysis revealed an altered composition of gut microbiota between CD and non-CD phenotypes. Furthermore, we observed a decrease in the levels of Phylum-Bacteroidete, Class-Bacteroidia, and Order-Bacteroidales in the CD group and an increase in the Genus-Allobaculum level after WBRT. Pretreatment with antibiotics caused a significant decrease in the level of Phylum-TM7 01, whereas an increase in the levels of Class-Gammaproteobacteria, Order-Enterobacteriales, and Species-Escherichia coli. After pretreatment with probiotics, the levels of Phylum-Cyanobacteria, Class-4C0d-2, and Order-YS2 were decreased, while the levels of Family-Bacteroidaceae, Genus-Bacteroides, and Species-Parabacteroides distasonis were increased. CONCLUSIONS: WBRT-induced CD might be highly related to abnormal composition of gut microbiota. Strategies improving the composition of the gut microbiota may provide beneficial effects on CD in individuals exposed to WBRT.


Assuntos
Encéfalo/fisiologia , Encéfalo/efeitos da radiação , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/microbiologia , Microbioma Gastrointestinal/fisiologia , Microbioma Gastrointestinal/efeitos da radiação , Animais , Encéfalo/efeitos dos fármacos , Disfunção Cognitiva/psicologia , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Aprendizagem em Labirinto/efeitos da radiação , Camundongos , Camundongos Endogâmicos C57BL , Prebióticos/administração & dosagem , Probióticos/administração & dosagem
14.
Sci Rep ; 10(1): 8833, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32483249

RESUMO

Synchrotron facilities produce ultra-high dose rate X-rays that can be used for selective cancer treatment when combined with micron-sized beams. Synchrotron microbeam radiation therapy (MRT) has been shown to inhibit cancer growth in small animals, whilst preserving healthy tissue function. However, the underlying mechanisms that produce successful MRT outcomes are not well understood, either in vitro or in vivo. This study provides new insights into the relationships between dosimetry, radiation transport simulations, in vitro cell response, and pre-clinical brain cancer survival using intracerebral gliosarcoma (9LGS) bearing rats. As part of this ground-breaking research, a new image-guided MRT technique was implemented for accurate tumor targeting combined with a pioneering assessment of tumor dose-coverage; an essential parameter for clinical radiotherapy. Based on the results of our study, we can now (for the first time) present clear and reproducible relationships between the in vitro cell response, tumor dose-volume coverage and survival post MRT irradiation of an aggressive and radioresistant brain cancer in a rodent model. Our innovative and interdisciplinary approach is illustrated by the results of the first long-term MRT pre-clinical trial in Australia. Implementing personalized synchrotron MRT for brain cancer treatment will advance this international research effort towards clinical trials.


Assuntos
Neoplasias Encefálicas/radioterapia , Gliossarcoma/radioterapia , Animais , Encéfalo/patologia , Encéfalo/efeitos da radiação , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Modelos Animais de Doenças , Gliossarcoma/mortalidade , Gliossarcoma/patologia , Masculino , Ratos , Ratos Endogâmicos F344 , Taxa de Sobrevida , Síncrotrons , Microtomografia por Raio-X , Raios X
15.
Clin Exp Metastasis ; 37(3): 435-444, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32377943

RESUMO

Brain metastasis (BM) affects up to one-third of adults with cancer and carries a historically bleak prognosis. Despite advances in stereotactic radiosurgery (SRS), rates of in-field recurrence (IFR) after SRS range from 10 to 25%. High rates of neurologic death have been reported after SRS failure, particularly for recurrences deep in the brain and surgically inaccessible. Laser interstitial thermal therapy (LITT) is an emerging option in this setting, but its ability to prevent a neurologic death is unknown. In this study, we investigate the causes of death among patients with BM who undergo LITT for IFR after SRS. We conducted a single institution retrospective case series of patients with BM who underwent LITT for IFR after SRS. Clinical and demographic data were collected via chart review. The primary endpoint was cause of death. Between 2010 and 2018, 70 patients with BM underwent LITT for IFR after SRS. Median follow-up after LITT was 12.0 months. At analysis, 49 patients died; a cause was determined in 44. Death was neurologic in 20 patients and non-neurologic in 24. The 24-month cumulative incidence of neurologic and non-neurologic death was 35.1% and 38.6%, respectively. Etiologies of neurologic death included local recurrence (n = 7), recovery failure (n = 7), distant progression (n = 5), and other (n = 1). Among our patient population, LITT provided the ability to stabilize neurologic disease in up to 2/3 of patients. For IFR after SRS, LITT may represent a reasonable treatment strategy for select patients. Additional work is necessary to determine the extent to which LITT can prevent neurologic death after recurrence of BM.


Assuntos
Morte Encefálica/diagnóstico , Neoplasias Encefálicas/terapia , Hipertermia Induzida , Recidiva Local de Neoplasia/terapia , Radiocirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/efeitos da radiação , Morte Encefálica/patologia , Morte Encefálica/fisiopatologia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/secundário , Causas de Morte , Progressão da Doença , Feminino , Seguimentos , Humanos , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/fisiopatologia , Seleção de Pacientes , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
16.
J Neuropathol Exp Neurol ; 79(7): 791-799, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32447392

RESUMO

Cerebral radiation necrosis (CRN) is a delayed complication of radiosurgery that can result in severe neurological deficits. The biological changes leading to necrotic damage may identify therapeutic targets for this complication. Connexin43 expression associated with chronic inflammation may presage the development of CRN. A mouse model of delayed CRN was used. The left hemispheres of adult female mice were irradiated with single-fraction, high-dose radiation using a Leksell Gamma Knife. The brains were collected 1 and 4 days, and 1-3 weeks after the radiation. The expression of connexin43, interleukin-1ß (IL-1ß), GFAP, isolectin B-4, and fibrinogen was evaluated using immunohistochemical staining and image analysis. Compared with the baseline, the area of connexin43 and IL-1ß staining was increased in ipsilateral hemispheres 4 days after radiation. Over the following 3 weeks, the density of connexin43 gradually increased in parallel with progressive increases in GFAP, isolectin B-4, and fibrinogen labeling. The overexpression of connexin43 in parallel with IL-1ß spread into the affected brain regions first. Further intensified upregulation of connexin43 was associated with escalated astrocytosis, microgliosis, and blood-brain barrier breach. Connexin43-mediated inflammation may underlie radiation necrosis and further investigation of connexin43 hemichannel blockage is merited for the treatment of CRN.


Assuntos
Lesões Encefálicas/metabolismo , Encéfalo/metabolismo , Encéfalo/efeitos da radiação , Conexina 43/biossíntese , Lesões por Radiação/metabolismo , Animais , Encéfalo/patologia , Lesões Encefálicas/genética , Lesões Encefálicas/patologia , Conexina 43/genética , Feminino , Expressão Gênica , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Camundongos Endogâmicos BALB C , Necrose/metabolismo , Necrose/patologia , Lesões por Radiação/genética , Lesões por Radiação/patologia
17.
PLoS One ; 15(5): e0228119, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32407389

RESUMO

Simulating transcranial electric stimulation is actively researched as knowledge about the distribution of the electrical field is decisive for understanding the variability in the elicited stimulation effect. Several software pipelines comprehensively solve this task in an automated manner for standard use-cases. However, simulations for non-standard applications such as uncommon electrode shapes or the creation of head models from non-optimized T1-weighted imaging data and the inclusion of irregular structures are more difficult to accomplish. We address these limitations and suggest a comprehensive workflow to simulate transcranial electric stimulation based on open-source tools. The workflow covers the head model creation from MRI data, the electrode modeling, the modeling of anisotropic conductivity behavior of the white matter, the numerical simulation and visualization. Skin, skull, air cavities, cerebrospinal fluid, white matter, and gray matter are segmented semi-automatically from T1-weighted MR images. Electrodes of arbitrary number and shape can be modeled. The meshing of the head model is implemented in a way to preserve the feature edges of the electrodes and is free of topological restrictions of the considered structures of the head model. White matter anisotropy can be computed from diffusion-tensor imaging data. Our solver application was verified analytically and by contrasting the tDCS simulation results with that of other simulation pipelines (SimNIBS 3.0, ROAST 3.0). An agreement in both cases underlines the validity of our workflow. Our suggested solutions facilitate investigations of irregular structures in patients (e.g. lesions, implants) or new electrode types. For a coupled use of the described workflow, we provide documentation and disclose the full source code of the developed tools.


Assuntos
Encéfalo/fisiologia , Sistema Nervoso Central/fisiologia , Cabeça/fisiologia , Estimulação Transcraniana por Corrente Contínua , Algoritmos , Anisotropia , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos da radiação , Sistema Nervoso Central/diagnóstico por imagem , Sistema Nervoso Central/efeitos da radiação , Imagem de Tensor de Difusão , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/efeitos da radiação , Cabeça/diagnóstico por imagem , Cabeça/efeitos da radiação , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Modelos Teóricos , Substância Branca/diagnóstico por imagem , Substância Branca/efeitos da radiação , Fluxo de Trabalho
18.
Environ Toxicol ; 35(10): 1137-1145, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32463565

RESUMO

The low dose of radiation (LDR) has received growing attention for its beneficial neuroprotective effect. This study was designed to investigate the enhancing effect of LDR on the antidepressant potential of resveratrol against diazepam-induced depression in mice. Female mice divided into five groups; control, diazepam (2 mg/kg), LDR (0.5Gy) + diazepam, resveratrol (20 mg/kg) + diazepam, LDR + resveratrol+diazepam. Mice received diazepam showed depressive symptoms as evidenced by decreased locomotor activity in the open field and increased immobility time in the forced swimming and tail suspension tests integrated with a marked decline in biogenic amines (serotonin, norepinephrine, and dopamine) in brain tissues. These effects were ameliorated by LDR or resveratrol administration demonstrating an antidepressant activity. Interestingly, LDR triggered the antidepressant effect of resveratrol as it restored the changes in behavioral tests, neurotransmitters, and neuro-histoarchitecture. In conclusion, these findings suggested that LDR could be considered as a novel adjuvant that augmented the resveratrol antidepressant effect and might serve as a potential therapeutic approach for depression.


Assuntos
Antidepressivos/farmacologia , Comportamento Animal , Química Encefálica , Depressão/tratamento farmacológico , Raios gama , Fármacos Neuroprotetores/farmacologia , Resveratrol/farmacologia , Animais , Antidepressivos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/efeitos da radiação , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/efeitos da radiação , Química Encefálica/efeitos dos fármacos , Química Encefálica/efeitos da radiação , Feminino , Elevação dos Membros Posteriores , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Atividade Motora/efeitos da radiação , Fármacos Neuroprotetores/uso terapêutico , Neurotransmissores/metabolismo , Doses de Radiação , Resveratrol/uso terapêutico , Irradiação Corporal Total
19.
Phys Med Biol ; 65(10): 105011, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32235057

RESUMO

Positron emission tomography (PET) has been used for dose verification in charged particle therapy. The causes of washout of positron emitters by physiological functions should be clarified for accurate dose verification. In this study, we visualized the distribution of irradiated radioactive beams, 11C and 15O beams, in the rabbit whole-body using our original depth-of-interaction (DOI)-PET prototype to add basic data for biological washout effect correction. Time activity curves of the irradiated field and organs were measured immediately after the irradiations. All data were corrected for physical decay before further analysis. We also collected expired gas of the rabbit during beam irradiation and the energy spectrum was measured with a germanium detector. Irradiated radioactive beams into the brain were distributed to the whole body due to the biological washout process, and the implanted 11C and 15O ions were concentrated in the regions which had high blood volume. The 11C-labelled 11CO2 was detected in expired gas under the 11C beam irradiation, while no significant signal was detected under the 15O beam irradiation as a form of C15O2. Results suggested that the implanted 11C ions form molecules that diffuse out to the whole body by undergoing perfusion, then, they are incorporated into the blood-gas exchange in the respiratory system. This study provides basic data for modelling of the biological washout effect.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/efeitos da radiação , Radioisótopos de Carbono/metabolismo , Modelos Biológicos , Radioisótopos de Oxigênio/metabolismo , Tomografia por Emissão de Pósitrons , Animais , Radioisótopos de Carbono/farmacocinética , Radioisótopos de Oxigênio/farmacocinética , Coelhos , Distribuição Tecidual
20.
Int J Clin Oncol ; 25(7): 1432-1439, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32274614

RESUMO

BACKGROUND: Although whole brain radiation therapy (WBRT) is commonly used as first-line treatment for leptomeningeal carcinomatosis, the prognosis is uncertain despite treatment. Moreover, the benefit of WBRT for leptomeningeal carcinomatosis has not been adequately evaluated. Therefore, this study aimed to clarify the utility of WBRT for leptomeningeal carcinomatosis. METHODS: Consecutive patients who received WBRT for leptomeningeal carcinomatosis or brain metastasis from solid tumors between January 2008 and July 2017 were retrospectively evaluated. The overall survival, symptom relief, and adverse events were compared between patients with leptomeningeal carcinomatosis and those with brain metastasis after WBRT. RESULTS: Of the 277 treated patients, 204 patients (22 with leptomeningeal carcinomatosis and 182 with brain metastasis) were included in the study. The median overall survival was 440 days (95% confidence interval [CI] 0-931 days) for patients with leptomeningeal carcinomatosis and 322 days (95% CI 196-448 days) for those with brain metastasis (p = 0.972 on the log-rank test). On evaluating the overall survival of patients with leptomeningeal carcinomatosis, the prognostic factors of performance status 0-1, no extracranial metastasis, and no symptoms at the time of WBRT showed a significant survival advantage on univariate analysis. Among patients with leptomeningeal carcinomatosis, those with headache and nausea often showed improvement while those with depressed levels of consciousness and seizures did not. On comparing all-grade adverse events, vomiting and seizures were more frequent in patients with leptomeningeal carcinomatosis than in those with brain metastasis. CONCLUSIONS: WBRT was generally well tolerated and effective for treating patients with leptomeningeal carcinomatosis.


Assuntos
Carcinomatose Meníngea/radioterapia , Radioterapia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/patologia , Encéfalo/efeitos da radiação , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Feminino , Cefaleia/radioterapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Carcinomatose Meníngea/mortalidade , Pessoa de Meia-Idade , Prognóstico , Radioterapia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
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