Despite progresses in surgery, radiotherapy, and in chemotherapy, an effective curative treatment of gliomas does not yet exist. Mortality is still close to 100% and the average survival of patients ...with GBM is less than 1 year. The efficacy of current anti-cancer strategies in brain tumors is limited by the lack of specific therapies against malignant cells. Besides, the delivery of the drugs to brain tumors is limited by the presence of the blood brain barrier. The oncogenesis of gliomas is characterized by several biological processes and genetic alterations, involved in the neoplastic transformation. The modulation of gene expression to more levels, such as DNA, mRNA, proteins and transduction signal pathways, may be the most effective modality to down-regulate or silence some specific gene functions. Gliomas are characterized by extensive microvascular proliferation and a higher degree of vasculature. In malignant gliomas targeted therapies efficacy is low. In this complex field, it seems to be very important to improve specific selective drugs delivery systems. Drugs, antisense oligonucleotides, small interference RNAs, engineered monoclonal antibodies and other therapeutic molecules may diffuse into CNS overcoming the BBB. Nanotechnology could be used both to improve the treatment efficacy and to reduce the adverse side effects.
Neuro Rose, Nikolas S
2013., 20130221, 2013, 2013-02-21
eBook
The brain sciences are influencing our understanding of human behavior as never before, from neuropsychiatry and neuroeconomics to neurotheology and neuroaesthetics. Many now believe that the brain ...is what makes us human, and it seems that neuroscientists are poised to become the new experts in the management of human conduct.Neurodescribes the key developments--theoretical, technological, economic, and biopolitical--that have enabled the neurosciences to gain such traction outside the laboratory. It explores the ways neurobiological conceptions of personhood are influencing everything from child rearing to criminal justice, and are transforming the ways we "know ourselves" as human beings. In this emerging neuro-ontology, we are not "determined" by our neurobiology: on the contrary, it appears that we can and should seek to improve ourselves by understanding and acting on our brains.
Neuroexamines the implications of this emerging trend, weighing the promises against the perils, and evaluating some widely held concerns about a neurobiological "colonization" of the social and human sciences. Despite identifying many exaggerated claims and premature promises,Neuroargues that the openness provided by the new styles of thought taking shape in neuroscience, with its contemporary conceptions of the neuromolecular, plastic, and social brain, could make possible a new and productive engagement between the social and brain sciences.
Copyright note: Reproduction, including downloading of Joan Miro works is prohibited by copyright laws and international conventions without the express written permission of Artists Rights Society (ARS), New York.
Divided Brains Rogers, Lesley J.; Vallortigara, Giorgio; Andrew, Richard J.
01/2013
eBook
Asymmetry of the brain and behaviour (lateralization) has traditionally been considered unique to humans. However, research has shown that this phenomenon is widespread throughout the vertebrate ...kingdom and found even in some invertebrate species. A similar basic plan of organisation exists across vertebrates. Summarising the evidence and highlighting research from the last twenty years, the authors discuss lateralization from four perspectives - function, evolution, development and causation - covering a wide range of animals, including humans. The evolution of lateralization is traced from our earliest ancestors, through fish and reptiles to birds and mammals. The benefits of having a divided brain are discussed, as well as the influence of experience on its development. A final chapter discusses outstanding problems and areas for further investigation. Experts in this field, the authors present the latest scientific knowledge clearly and engagingly, making this a valuable tool for anyone interested in the biology and behaviour of brain asymmetries.
Subarachnoid hemorrhage (SAH) is a subtype of stroke with high mortality and morbidity due to the lack of effective therapy. Atorvastatin has been reported to alleviate early brain injury (EBI) ...following subarachnoid hemorrhage (SAH) via reducing reactive oxygen species, antiapoptosis, regulated autophagy, and neuroinflammation. Which was the related to the pyroptosis? Pyroptosis can be defined as a highly specific inflammatory programmed cell death, distinct from classical apoptosis and necrosis. However, the precise role of pyroptosis in atorvastatin‐mediated neuroprotection following SAH has not been confirmed. The present study aimed to investigate the neuroprotection and potential molecular mechanisms of atorvastatin in the SAH‐induced EBI via regulating neural pyroptosis using the filament perforation model of SAH in male C57BL/6 mice, and the hemin‐induced neuron damage model in HT‐22. Atorvastatin or vehicle was administrated 2 h after SAH and hemin‐induced neuron damage. The mortality, neurological score, brain water content, and neuronal death were evaluated. The results show that the atorvastatin treatment markedly increased survival rate, neurological score, greater survival of neurons, downregulated the protein expression of NLRP1, cleaved caspase‐1, interleukin‐1β (IL‐1β), and IL‐18, which indicated that atorvastatin‐inhibited pyroptosis and neuroinflammation, ameliorated neuron death in vivo/vitro subjected to SAH. Taken together, this study demonstrates that atorvastatin improved the neurological outcome in rats and reduced the neuron death by against neural pyroptosis and neuroinflammation.
This study demonstrates that atorvastatin improved the neurological outcome in rats and reduced the neuron death by against neural pyroptosis and neuroinflammation.
•An efficient 11-layers deep, multi-scale, 3D CNN architecture.•A novel training strategy that significantly boosts performance.•The first employment of a 3D fully connected CRF for ...post-processing.•State-of-the-art performance on three challenging lesion segmentation tasks.•New insights into the automatically learned intermediate representations.
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We propose a dual pathway, 11-layers deep, three-dimensional Convolutional Neural Network for the challenging task of brain lesion segmentation. The devised architecture is the result of an in-depth analysis of the limitations of current networks proposed for similar applications. To overcome the computational burden of processing 3D medical scans, we have devised an efficient and effective dense training scheme which joins the processing of adjacent image patches into one pass through the network while automatically adapting to the inherent class imbalance present in the data. Further, we analyze the development of deeper, thus more discriminative 3D CNNs. In order to incorporate both local and larger contextual information, we employ a dual pathway architecture that processes the input images at multiple scales simultaneously. For post-processing of the network’s soft segmentation, we use a 3D fully connected Conditional Random Field which effectively removes false positives. Our pipeline is extensively evaluated on three challenging tasks of lesion segmentation in multi-channel MRI patient data with traumatic brain injuries, brain tumours, and ischemic stroke. We improve on the state-of-the-art for all three applications, with top ranking performance on the public benchmarks BRATS 2015 and ISLES 2015. Our method is computationally efficient, which allows its adoption in a variety of research and clinical settings. The source code of our implementation is made publicly available.
Traumatic brain injuries (TBIs) account for the majority of injury-related deaths in the United States with roughly two million TBIs occurring annually. Due to the spectrum of severity and ...heterogeneity in TBIs, investigation into the secondary injury is necessary in order to formulate an effective treatment. A mechanical consequence of trauma involves dysregulation of the blood-brain barrier (BBB) which contributes to secondary injury and exposure of peripheral components to the brain parenchyma. Recent studies have shed light on the mechanisms of BBB breakdown in TBI including novel intracellular signaling and cell-cell interactions within the BBB niche. The current review provides an overview of the BBB, novel detection methods for disruption, and the cellular and molecular mechanisms implicated in regulating its stability following TBI.
Molecular pathophysiology of cerebral edema Stokum, Jesse A; Gerzanich, Volodymyr; Simard, J Marc
Journal of Cerebral Blood Flow & Metabolism,
03/2016, Letnik:
36, Številka:
3
Book Review, Journal Article
Recenzirano
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Advancements in molecular biology have led to a greater understanding of the individual proteins responsible for generating cerebral edema. In large part, the study of cerebral edema is the study of ...maladaptive ion transport. Following acute CNS injury, cells of the neurovascular unit, particularly brain endothelial cells and astrocytes, undergo a program of pre- and post-transcriptional changes in the activity of ion channels and transporters. These changes can result in maladaptive ion transport and the generation of abnormal osmotic forces that, ultimately, manifest as cerebral edema. This review discusses past models and current knowledge regarding the molecular and cellular pathophysiology of cerebral edema.
Brain Tumors Greenberg, Harry S
1999, 19990408, 1999-05-27, Letnik:
54
eBook
Written for neurologists and other physicians who participate in the diagnosis and treatment of brain tumors, this book synthesizes the authors' clinical experiences. The first seven chapters provide ...a foundation for tumor pathology, biology, radiology, and the treatment modalities of surgery, radiation therapy, and chemotherapy. The remaining eight chapters have a common format, reviewing the history, epidemiology, biology, pathology, clinical symptoms, differential diagnosis, treatment, prognosis, and complications of specific tumors.
Blood–brain/blood–tumor barriers (BBB and BTB) and interstitial transport may constitute major obstacles to the transport of therapeutics in brain tumors. In this study, we examined the impact of ...focused ultrasound (FUS) in combination with microbubbles on the transport of two relevant chemotherapy-based anticancer agents in breast cancer brain metastases at cellular resolution: doxorubicin, a nontargeted chemotherapeutic, and ado-trastuzumab emtansine (T-DM1), an antibody–drug conjugate. Using an orthotopic xenograft model of HER2-positive breast cancer brain metastasis and quantitative microscopy, we demonstrate significant increases in the extravasation of both agents (sevenfold and twofold for doxorubicin and T-DM1, respectively), and we provide evidence of increased drug penetration (>100 vs. <20 μm and 42 ± 7 vs. 12 ± 4 μm for doxorubicin and T-DM1, respectively) after the application of FUS compared with control (non-FUS). Integration of experimental data with physiologically based pharmacokinetic (PBPK) modeling of drug transport reveals that FUS in combination with microbubbles alleviates vascular barriers and enhances interstitial convective transport via an increase in hydraulic conductivity. Experimental data demonstrate that FUS in combination with microbubbles enhances significantly the endothelial cell uptake of the small chemotherapeutic agent. Quantification with PBPK modeling reveals an increase in transmembrane transport by more than two orders of magnitude. PBPK modeling indicates a selective increase in transvascular transport of doxorubicin through small vessel wall pores with a narrow range of sizes (diameter, 10–50 nm). Our work provides a quantitative framework for the optimization of FUS–drug combinations to maximize intratumoral drug delivery and facilitate the development of strategies to treat brain metastases.
The Microbiota-Gut-Brain Axis Cryan, John F; O'Riordan, Kenneth J; Cowan, Caitlin S M ...
Physiological reviews,
10/2019, Letnik:
99, Številka:
4
Journal Article
Recenzirano
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The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within ...and on our bodies) as one of the key regulators of gut-brain function and has led to the appreciation of the importance of a distinct microbiota-gut-brain axis. This axis is gaining ever more traction in fields investigating the biological and physiological basis of psychiatric, neurodevelopmental, age-related, and neurodegenerative disorders. The microbiota and the brain communicate with each other via various routes including the immune system, tryptophan metabolism, the vagus nerve and the enteric nervous system, involving microbial metabolites such as short-chain fatty acids, branched chain amino acids, and peptidoglycans. Many factors can influence microbiota composition in early life, including infection, mode of birth delivery, use of antibiotic medications, the nature of nutritional provision, environmental stressors, and host genetics. At the other extreme of life, microbial diversity diminishes with aging. Stress, in particular, can significantly impact the microbiota-gut-brain axis at all stages of life. Much recent work has implicated the gut microbiota in many conditions including autism, anxiety, obesity, schizophrenia, Parkinson's disease, and Alzheimer's disease. Animal models have been paramount in linking the regulation of fundamental neural processes, such as neurogenesis and myelination, to microbiome activation of microglia. Moreover, translational human studies are ongoing and will greatly enhance the field. Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.
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