Brain and Human Body Modeling

This open access book describes modern applications of computational human modeling with specific emphasis in the areas of neurology and neuroelectromagnetics, depression and cancer treatments, radio-frequency studies and wireless communications. Special consideration is also given to the use of human modeling to the computational assessment of relevant regulatory and safety requirements. Readers working on applications that may expose human subjects to electromagnetic radiation will benefit from this book’s coverage of the latest developments in computational modelling and human phantom development to assess a given technology’s safety and efficacy in a timely manner. Describes construction and application of computational human models including anatomically detailed and subject specific models; Explains new practices in computational human modeling for neuroelectromagnetics, electromagnetic safety, and exposure evaluations; Includes a survey of modern applications for which computational human models are critical; Describes cellular-level interactions between the human body and electromagnetic fields

Brain and Human Body Modeling

This open access book describes modern applications of computational human modeling with specific emphasis in the areas of neurology and neuroelectromagnetics, depression and cancer treatments, radio-frequency studies and wireless communications. Special consideration is also given to the use of human modeling to the computational assessment of relevant regulatory and safety requirements. Readers working on applications that may expose human subjects to electromagnetic radiation will benefit from this book’s coverage of the latest developments in computational modelling and human phantom development to assess a given technology’s safety and efficacy in a timely manner. Describes construction and application of computational human models including anatomically detailed and subject specific models; Explains new practices in computational human modeling for neuroelectromagnetics, electromagnetic safety, and exposure evaluations; Includes a survey of modern applications for which computational human models are critical; Describes cellular-level interactions between the human body and electromagnetic fields

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 385)

This bibliography lists 536 reports, articles and other documents introduced into the NASA Scientific and Technical Information System Database. Subject coverage includes: aerospace medicine and physiology, life support systems and man/system technology, protective clothing, exobiology and extraterrestrial life, planetary biology, and flight crew behavior and performance

Dissection of Affective Catecholamine Circuits Using Traditional and Wireless Optogenetics

Parsing the complexity of the mammalian brain has challenged neuroscientists for thousands of years. In the early 21st century, advances in materials science and neuroscience have enabled unprecedented control of neural circuitry. In particular, cell-type selective manipulations, such as those with optogenetics and chemogenetics, routinely provide answers to previously intractable neurobiological questions in the intact, behaving animal. In this two-part dissertation, I first introduce new minimally invasive, wireless technology to perturb neural activity in the ventral tegmental area dopaminergic system of freely moving animals. I report a series of novel devices for studying and perturbing intact neural systems through optogenetics, microfluidic pharmacology, and electrophysiology. Unlike optogenetic approaches that rely on rigid, glass fiber optics coupled to external light sources, these novel devices utilize flexible substrates to carry microscale, inorganic light emitting diodes (μ-ILEDs), multimodal sensors, and/or microfluidic channels into the brain. Each class of device can be wirelessly controlled, enabling studies in freely behaving mice and achieving previously untenable control of catecholamine neural circuitry. In the second part of this dissertation, I apply existing cell-type selective approaches to dissect the role of the locus coeruleus noradrenergic (LC-NE) system in anxiety-like and aversive behaviors. The LC-NE system is one of the first systems engaged following a stressful event. While LC-NE neurons are known to be activated by many different stressors, the underlying neural circuitry and the role of this activity in generating stress-induced anxiety has not been elucidated until now. I demonstrate that increased tonic activity of LC-NE neurons is both necessary and sufficient for stress-induced anxiety; a behavior which is driven by LC projections to the basolateral amygdala. Furthermore, this activity and behavior is elicited by corticotropin releasing hormone-containing afferent inputs into the LC from the central amygdala. These studies position the LC-NE system as a critical mediator of acute stress-induced anxiety and offer a potential intervention for preventing stress-related affective disorders. Together these two objectives provide a rich technological toolbox for neuroscientists and yield important knowledge of how small catecholamine structures with widespread forebrain innervation can selectively mediate higher order behaviors

Aerospace medicine and biology: A cumulative index to a continuing bibliography (supplement 371)

This publication is a cumulative index to the abstracts contained in Supplements 359 through 370 of Aerospace Medicine and Biology: A Continuing Bibliography. It includes seven indexes: subject, personal author, corporate source, foreign technology, contract number, report number, and accession number

Aerospace medicine and biology: A cumulative index to a continuing bibliography (supplement 384)

This publication is a cumulative index to the abstracts contained in Supplements 372 through 383 of Aerospace Medicine and Biology: A Continuing Bibliography. It includes seven indexes: subject, personal author, corporate source, foreign technology, contract number, report number, and accession number

Spacelab Science Results Study

Beginning with OSTA-1 in November 1981 and ending with Neurolab in March 1998, a total of 36 Shuttle missions carried various Spacelab components such as the Spacelab module, pallet, instrument pointing system, or mission peculiar experiment support structure. The experiments carried out during these flights included astrophysics, solar physics, plasma physics, atmospheric science, Earth observations, and a wide range of microgravity experiments in life sciences, biotechnology, materials science, and fluid physics which includes combustion and critical point phenomena. In all, some 764 experiments were conducted by investigators from the U.S., Europe, and Japan. The purpose of this Spacelab Science Results Study is to document the contributions made in each of the major research areas by giving a brief synopsis of the more significant experiments and an extensive list of the publications that were produced. We have also endeavored to show how these results impacted the existing body of knowledge, where they have spawned new fields, and if appropriate, where the knowledge they produced has been applied

Exploration of an electro-magneto-responsive polymeric drug delivery system for enhanced nose-to-brain delivery

A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand in fulfilment of the requirements for the degree of Doctor of PhilosophyDelivering drugs to the brain for the treatment of brain diseases has been fraught with low bioavailability of drugs due to the Blood-Brain Barrier (BBB). The intranasal (IN) route of delivery has purportedly been given recognition as an alternative route of delivering drugs to the brain with improved bioavailability if the nose-to-brain option is considered. However, drugs administered through the nasal mucosa suffer some challenges such as mucocilliary clearance, enzymatic degradation, inability of a controllable drug release to give a precise dose, resulting in frequent dosing and absorption into the systemic circulation through the blood rich vessels in the mucosa, thus facing the BBB challenge. The aim of this study was to develop a novel Nano-co-Plex (NCP), a magnetic nano-carrier loaded with a therapeutic agent which is further incorporated into a nasal thermosensitive electro-responsive mucogel (TERM) for in situ gelling, for electroactuated release of the incorporated drug-loaded NCP in a controllable “on-off” pulsatile manner, which is achieved with the aid of an external electric stimulation (ES). The released drug-loaded NCP was then targeted to the brain via a direct nose-to-brain drug delivery pathway with the aid of an external magnetic field (MF) for rapid transportation. The ES was brought about by applying a 5V potential difference (PD) using electrodes on the nose and the external MF would then be applied by placing a magnetic headband on the head of the patient. In this research, the drug-loaded NCP was prepared by firstly synthesizing iron oxide nanoparticles (Magnetite) which were then coated with Polyplex; a polymeric complex fabricated employing polyvinyl alcohol (PVA), polyethyleneimine (PEI) and fIuorecein isothiocyanate (FITC). The coated magnetite was thereafter loaded with Carmustine (BCNU), an effective drug commonly used in brain tumor treatment, to formulate the BCNU-NCP. The TERM was prepared by blending a thermosensitive polymer, Pluronic F127 (F127) with mucoadhesive polymers, chitosan (CS) and hydroxypropyl methylcellulose (HPMC). Polyaniline (PANI) was included in the blend as the electo-active moiety of the formulation. Finally, the BCNU-NCP was incorporated into the gel to form a Nanogel- Composite. A Box–Behnken design model was employed for the optimization of the Nanogel Composite. TERM, BCNU-NCP and Nanogel Composite were characterized employing Thermogravimetric analysis (TGA), Superconducting Quantum Interference Device (SQUID) magnetometry, Fourier Transform Infrared Spectroscopy (FTIR), Nuclear Magnetic Resonance (NMR), X-ray Diffractometry (XRD), Scanning Electron Microscopy (SEM), Cyclic Voltammetry (CV), Transmission Electron Microscopy (TEM), Rheological, Porositometry, Textural and Zetasize analyses. In vitro drug release, ex vivo permeation and in vivo studies were performed. The BCNU-NCP was found to be paramagnetic with a magnetization value of 61emu/g, possessing a mixture of spherical and hexagonal shaped core-shell nanoparticles of size 30-50nm with zeta potential of +32 ±2mV. The NCP displayed a high degree of crystallinity with 32% Polyplex coating. The loading capacity of NCP was 176.86μg BCNU/mg of the carrier and maximum release of 75.8% of the loaded BCNU was achieved after 24 hours. FTIR and NMR confirmed the conjugation of PVA and PEI of the Polyplex at a ratio of 1:4. Cytotoxicity of the BCNU-loaded Nano-co-Plex displayed superiority over the conventional BCNU towards human glioblastoma (HG) A170 cells. Cell studies revealed enhanced uptake and internalization of BCNU-NCP in HG A170 cells in the presence of an external MF. BCNU-NCP was found to be non-toxic to healthy brain cells. A thermally stable gel with desirable rheological and mucoadhesive properties was developed. The results revealed gelation temperature of 27.5±0.5°C with a porous morphology. Nanogel Composite possesses electroactive properties and shows response to ES and releases incorporated BCNU-NCP in an “on-off” pulsatile drug release profile upon application of a 5V PD. The in vitro release studies showed an average release of BCNU-NCP per release cycle to be 10.28%. Ex vivo permeation studies were performed using a freshly excised nasal tissue of the New Zealand white rabbit; the results showed that BCNU-NCP was able to permeate through the nasal tissue at a 6 times greater amount in the presence of a MF than in the absence of MF. BCNU concentration was found to be high in the brain and CSF of rabbit when the Nanogel Composite is intranasally administered compared to the IV injection of the conventional BCNU. Furthermore, application of the MF was found to increase the concentration of BCNU in the brain and CSF of the rabbit. The result of Field Emission Electron Probe Micro Analyzer (FE EPMA) was further used to confirm the presence of NCP in the rabbit brain tissue. Histopathological results indicated mild lesions in the nasal mucosa of the rabbit after IN administration of Nanogel Composite. The results of the in vitro, ex vivo and the in vivo proved that the Nanogel Composite is superior in delivering BCNU into the brain than the conventional drug delivery system for the treatment of brain tumor as it was able to release the therapeutic agent in a controllable manner. The MF applied aided drug to be targeted and rapidly transported to the brain via a direct nose-to-brain pathway thereby circumventing the BBB and increasing bioavailability of drug in the brain. This vehicle may also be used to deliver other similar therapeutic agents into the brain for the treatment of various brain diseases.MB201