scholarly journals Mathematical modeling of therapeutic neural stem cell migration in mouse brain with and without brain tumors

2022 ◽  
Vol 19 (3) ◽  
pp. 2592-2615
Author(s):  
Justin Gomez ◽  
◽  
Nathanael Holmes ◽  
Austin Hansen ◽  
Vikram Adhikarla ◽  
...  

<abstract><p>Neural stem cells (NSCs) offer a potential solution to treating brain tumors. This is because NSCs can circumvent the blood-brain barrier and migrate to areas of damage in the central nervous system, including tumors, stroke, and wound injuries. However, for successful clinical application of NSC treatment, a sufficient number of viable cells must reach the diseased or damaged area(s) in the brain, and evidence suggests that it may be affected by the paths the NSCs take through the brain, as well as the locations of tumors. To study the NSC migration in brain, we develop a mathematical model of therapeutic NSC migration towards brain tumor, that provides a low cost platform to investigate NSC treatment efficacy. Our model is an extension of the model developed in Rockne et al. (PLoS ONE 13, e0199967, 2018) that considers NSC migration in non-tumor bearing naive mouse brain. Here we modify the model in Rockne et al. in three ways: (i) we consider three-dimensional mouse brain geometry, (ii) we add chemotaxis to model the tumor-tropic nature of NSCs into tumor sites, and (iii) we model stochasticity of migration speed and chemosensitivity. The proposed model is used to study migration patterns of NSCs to sites of tumors for different injection strategies, in particular, intranasal and intracerebral delivery. We observe that intracerebral injection results in more NSCs arriving at the tumor site(s), but the relative fraction of NSCs depends on the location of injection relative to the target site(s). On the other hand, intranasal injection results in fewer NSCs at the tumor site, but yields a more even distribution of NSCs within and around the target tumor site(s).</p></abstract>

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2104 ◽  
Author(s):  
Eleonora Ficiarà ◽  
Shoeb Anwar Ansari ◽  
Monica Argenziano ◽  
Luigi Cangemi ◽  
Chiara Monge ◽  
...  

Magnetic Oxygen-Loaded Nanobubbles (MOLNBs), manufactured by adding Superparamagnetic Iron Oxide Nanoparticles (SPIONs) on the surface of polymeric nanobubbles, are investigated as theranostic carriers for delivering oxygen and chemotherapy to brain tumors. Physicochemical and cyto-toxicological properties and in vitro internalization by human brain microvascular endothelial cells as well as the motion of MOLNBs in a static magnetic field were investigated. MOLNBs are safe oxygen-loaded vectors able to overcome the brain membranes and drivable through the Central Nervous System (CNS) to deliver their cargoes to specific sites of interest. In addition, MOLNBs are monitorable either via Magnetic Resonance Imaging (MRI) or Ultrasound (US) sonography. MOLNBs can find application in targeting brain tumors since they can enhance conventional radiotherapy and deliver chemotherapy being driven by ad hoc tailored magnetic fields under MRI and/or US monitoring.


2021 ◽  
Author(s):  
◽  
C. J. González Leal

NeuroPort is a low cost customized biodevice for minimal invasion surgeries designed within Servicio Neurocirugía UANL and Departamento de Ingeniería Biomédica; and manufactured by stereolithography, a high- resolution 3D printing method. This biodevice provides a channel of approach for subcortical and intraventricular cerebral surgical procedures with an intended use in the treatment of diseases such as brain tumors, anomalies or vascular malformations, parenchymal hematomas, among others. It has a design that minimizes tissue damage by displacing the tissues of the brain during the advance toward the desired abnormality; in addition to its integration with neuronavigational equipment and its own lighting system. All these features designed to make the surgical procedure faster and safer for the patient, facilitating the work of the neurosurgeon.


2012 ◽  
Vol 44 (15) ◽  
pp. 778-785 ◽  
Author(s):  
Jacqueline A. Gleave ◽  
Michael D. Wong ◽  
Jun Dazai ◽  
Maliha Altaf ◽  
R. Mark Henkelman ◽  
...  

The structural organization of the brain is important for normal brain function and is critical to understand in order to evaluate changes that occur during disease processes. Three-dimensional (3D) imaging of the mouse brain is necessary to appreciate the spatial context of structures within the brain. In addition, the small scale of many brain structures necessitates resolution at the ∼10 μm scale. 3D optical imaging techniques, such as optical projection tomography (OPT), have the ability to image intact large specimens (1 cm3) with ∼5 μm resolution. In this work we assessed the potential of autofluorescence optical imaging methods, and specifically OPT, for phenotyping the mouse brain. We found that both specimen size and fixation methods affected the quality of the OPT image. Based on these findings we developed a specimen preparation method to improve the images. Using this method we assessed the potential of optical imaging for phenotyping. Phenotypic differences between wild-type male and female mice were quantified using computer-automated methods. We found that optical imaging of the endogenous autofluorescence in the mouse brain allows for 3D characterization of neuroanatomy and detailed analysis of brain phenotypes. This will be a powerful tool for understanding mouse models of disease and development and is a technology that fits easily within the workflow of biology and neuroscience labs.


1984 ◽  
Vol 92 (2) ◽  
pp. 165-175 ◽  
Author(s):  
G. R. Smith ◽  
Janet C. Oliphant ◽  
R. Parsons

SUMMARYIntracerebral inoculation was more effective than intraperitoneal, intravenous or subcutaneous inoculation as a means of producing lethal infections withFusobacterium necrophorumin mice. Strains varied in virulence but, of five examined, two had LD50 values as low asca. 8000 and 14000 viable organisms. Profuse bacterial multiplication in the brain was demonstrated. Intravenous vaccination with a single large dose of heat-killed whole culture or washed bacterial cells failed to protect against intracerebral challenge.Intracerebral injection of other fusobacteria (F. nucleatum, F. variumandF. necrogenes) and of 22 strains belonging to 10Bacteroidesspp. was without apparent effect on mice, except for a slight transient illness in some animals givenB. fragilis. This organism (five strains) differed from the otherBacteroidesspp. tested, which included eight strains belonging to the fragilis group, in being eliminated more slowly from the mouse brain – a point that may be relevant to the special pathogenicity ofB. fragilisin endogenous infections in man. There was no evidence thatB. fragilismultiplied in the brain or that intravenous vaccination with a large dose of heat-killed homologous culture affected the rate at which it was eliminated.


2021 ◽  
Author(s):  
Batuhan Sözer ◽  
Alperen Sözer ◽  
Mustafa Çağlar Şahin ◽  
Kerem Nernekli ◽  
Şule Eylem Erdoğan ◽  
...  

<p>Early diagnosis of brain tumors is extremely important, and shortening the interval between the acquisition of MRI images and reporting of the results is critical for patients. In the diagnosis of brain tumors, CT and MRI are some of the core diagnostic techniques used today. Our main goal is to reduce the workload of radiologists by developing a neural network that segments MRI images of the brain so we propose a multi-path segmentation algorithm based on U-Net architecture that uses residual extended skip blocks. Our proposed model is trained and tested with Gazi Brains 2020 Dataset. We evaluated the results using the dice similarity coefficient and compared the results with other segmentation algorithms and saw that our proposed model has comparatively better results. Our proposed model is using T1-Weighted, T2-Weighted, and Flair MRI images together as inputs, whereas other segmentation models, are using T2-Weighted or Flair MRI images as input. Implementation of the model and trained models are available at </p> <p><b>https://github.com/batuhansozer/brain-segmentation-with-novel-multi-path-model</b></p>


Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 96
Author(s):  
Hyung Shik Kim ◽  
Dong Yun Lee

The current treatment for malignant brain tumors includes surgical resection, radiotherapy, and chemotherapy. Nevertheless, the survival rate for patients with glioblastoma multiforme (GBM) with a high grade of malignancy is less than one year. From a clinical point of view, effective treatment of GBM is limited by several challenges. First, the anatomical complexity of the brain influences the extent of resection because a fine balance must be struck between maximal removal of malignant tissue and minimal surgical risk. Second, the central nervous system has a distinct microenvironment that is protected by the blood–brain barrier, restricting systemically delivered drugs from accessing the brain. Additionally, GBM is characterized by high intra-tumor and inter-tumor heterogeneity at cellular and histological levels. This peculiarity of GBM-constituent tissues induces different responses to therapeutic agents, leading to failure of targeted therapies. Unlike surgical resection and radiotherapy, photodynamic therapy (PDT) can treat micro-invasive areas while protecting sensitive brain regions. PDT involves photoactivation of photosensitizers (PSs) that are selectively incorporated into tumor cells. Photo-irradiation activates the PS by transfer of energy, resulting in production of reactive oxygen species to induce cell death. Clinical outcomes of PDT-treated GBM can be advanced in terms of nanomedicine. This review discusses clinical PDT applications of nanomedicine for the treatment of GBM.


1988 ◽  
Vol 167 (2) ◽  
pp. 730-735 ◽  
Author(s):  
H G Ljunggren ◽  
T Yamasaki ◽  
P Collins ◽  
G Klein ◽  
K Kärre

H-2-deficient (H-2-) tumor variants were accepted equally well compared with H-2+ wild-type cells in the brain of syngeneic mice, while the H-2- cells were selectively eliminated when inoculated extracranially. This indicates a specific absence or suppression of the defense against MHC class I-deficient cells in the brain, suggested to be mediated by NK cells. In contrast, T cell-mediated immune reactions could clearly be detected in the brain under the same experimental conditions. This was shown in control experiments where H-2+ tumor cells were rejected from the brain of preimmunized or allogeneic mice. The present findings may be important for the understanding of neurotropic virus infections, immunology and immunotherapy of brain tumors, as well as for the growing interest in tissue grafting within the central nervous system.


2019 ◽  
Vol 1 (1) ◽  
pp. 1-19
Author(s):  
Mark Tommerdahl ◽  
Rachel Lensch ◽  
Eric Francisco ◽  
Jameson Holden ◽  
Oleg Favorov

Background. A large number of neurological disorders (neurodegenerative, neurodevelopmental or trauma induced) are difficult to diagnose or assess, thus limiting treatment efficacy.  Existing solutions and products for this need are costly, extremely slow, often invasive, and in many cases fail to definitively (and quantitatively) diagnose or assess treatment.  Advances. For the past decade, we have been developing what we consider to be an innovative low-cost sensory testing device (the Brain Gauge) that non-invasively assesses the central nervous system (CNS).  The objective has been to develop an inexpensive, highly accurate, simple to use device to assess brain health in all environments: in the clinic, at home, at work, on the battlefield or sports field.  The device is non-invasive, generates no harmful radiation, requires no chemicals nor exposure to dangerous substances.  The device does not require expensive disposables and does not involve the use of samples that require physical processing in a central laboratory.  Tests can be administered in a matter of minutes and do not require expert oversight.  The most recent versions of the technology are easily portable; the device is the size and shape of a computer mouse.  As such, the technology is particularly well suited to non-drug, non-radiation based alternative and in-home care.  The device and methods have been used in numerous studies of neurological cohorts that are often considered difficult to diagnose or assess objectively. Based on over a decade of studies (currently an ontological database of over 10,000 subjects and over 60 peer reviewed publications), the system can be used to enable clinicians to have a much better view of a patient’s CNS health status.  The diagnostic system delivers a battery of sensory based (tactile) tests that are conducted rapidly – much like an eye exam with verbal feedback – and the tests were  designed to be predominantly impacted by specific mechanisms of CNS information processing.  Because of the broad diversity of the questions addressed by the different metrics, combining the metrics allows for the generation of a unique individual CNS profile that appears to be very sensitive to neurological status. Outlook.  A review of the development of the system and the application of the method in basic and clinical research is provided to give readers an insight into why the methods were developed, how the methods work and what the methods can be optimally utilized for. The methods provide an objective means for clinicians and researchers to track brain health, and examples of case studies of tracking recovery from concussion as well as response to treatments are provided.


2005 ◽  
Vol 63 (2a) ◽  
pp. 252-258 ◽  
Author(s):  
Igor de Castro ◽  
Daniel de Holanda Christoph ◽  
Daniel Paes dos Santos ◽  
José Alberto Landeiro

The aim of this study is to introduce the fiber dissection technique and its importance in the comprehension of the three-dimensional intrinsic anatomy of the brain. A total of twenty brain hemispheres were dissected. Using Kingler's technique we demonstrated the intrinsic structures of the brain. The supra lateral aspect of the brain as well as the medial aspect were presented. The most important fiber systems were demonstrated. The use and comprehension of new neuroimaging techniques demand a better understanding of this fascinating anatomy. The knowledge acquired with this technique will improve our understanding of critical pathways of the central nervous system.


2017 ◽  
Vol 10 (05) ◽  
pp. 1743006 ◽  
Author(s):  
Sa Liu ◽  
Jun Nie ◽  
Yusha Li ◽  
Tingting Yu ◽  
Dan Zhu ◽  
...  

We present a three-dimensional (3D) isotropic imaging of mouse brain using light-sheet fluorescent microscopy (LSFM) in conjunction with a multi-view imaging computation. Unlike common single view LSFM is used for mouse brain imaging, the brain tissue is 3D imaged under eight views in our study, by a home-built selective plane illumination microscopy (SPIM). An output image containing complete structural information as well as significantly improved resolution ([Formula: see text]4 times) are then computed based on these eight views of data, using a bead-guided multi-view registration and deconvolution. With superior imaging quality, the astrocyte and pyramidal neurons together with their subcellular nerve fibers can be clearly visualized and segmented. With further including other computational methods, this study can be potentially scaled up to map the connectome of whole mouse brain with a simple light-sheet microscope.


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