Previous studies performed on myelinated nerve fibers have shown that a high frequency alternating current stimulus can block impulse conduction. The current threshold at which block occurs increases as the blocking frequency increases. Cable models based on the Hodgkin-Huxley model are consistent with these results. Recent experimental studies on unmyelinated nerve have shown that at higher frequencies, the block threshold decreases. When the block threshold is plotted as a function of frequency the resulting graph is distinctly nonmonotonic. Currently, all published models do not explain this behavior and the physiological mechanisms that create it are unknown. This difference in myelinated vs. unmyelinated block thresholds at high frequencies could have numerous clinical applications, such as chronic pain management. A large body of literature has shown that the specific capacitance of biological tissue decreases at frequencies in the kHz range or higher. Prior research has shown that introducing a frequency-dependent capacitance (FDC) to the Hodgkin-Huxley model will attenuate the block threshold at higher frequencies, but not to the extent that was seen in the experiments. This model was limited by the methods used to solve its higher order partial differential equation. The purpose of this thesis project is to develop a numerically stable method of incorporating the FDC into the model and to examine its effect on block threshold. The final, modified model will also be compared to the original model to ensure that the fundamental characteristics of action potential propagation remain unchanged.

Thesis (Ph. D.)--Cornell University, May, 2007. / Vita. Includes bibliographical references (leaves 162-189).

Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves 68-82).

Presented in this work is the investigation and successful illustration of a coupled model of the human nerve fiber. SPICE netlist code was utilized to describe the electrical properties of the human nervous membrane in tandem with COMSOL Multiphysics, a finite element analysis software tool. The initial research concentrated on the utilization of the Hodgkin-Huxley electrical circuit representation of the nerve fiber membrane. Further development of the project identified the need for a linear circuit model that more closely resembled the McNeal linearization model augmented by the work of Szlavik which better facilitated the coupling of both SPICE and COMSOL programs. Related literature was investigated and applied to validate the model. This combination of analysis tools allowed for the presentation of a consistent model and revealed that a coupled model produced not only a qualitatively comparable, but also a quantitatively comparable result to studies presented in the literature. All potential profiles produced during the simulation were compared against the literature in order to meet the purpose of presenting an advanced computational model of human neural recruitment and excitation. It was demonstrated through this process that the correct usage of neuron models within a two dimensional conductive space did allow for the approximate modeling of human neural electrical characteristics.

This work focuses on modeling a demyelinated Hodgkin and Huxley (HH) neuron with Simulated Program with Integrated Circuit Emphasis (SPICE) platform. Demyelinating disorders affect over 350,000 people in the U.S and understanding the demyelination process at the cellular level is necessary to find safe ways to treat the diseases [9]. Utilizing a previous SPICE model of an electrically small cell neuron developed by Szlavik [32], an extended core conductor myelinated neuron was produced in this work. The myelinated neuron developed has seven active Nodes of Ranvier (nodes) separated by a myelin sheath. The myelin sheath can be successfully modeled with a resistive and capacitive network known as internodes. Both the Nodes of Ranvier and internode equivalent circuits were implemented in P-SPICE sub-circuit library files. Properties of the neuron can be changed in the library files to simulate neurons of different electrical or geometric properties. Using the P-SPICE code developed in this work, a myelinated neuron’s action potential was simulated and the action potential at each node was recorded. The action potential at each node was uniform in amplitude and pulse width. The conduction velocity of the action potential was calculated to be 57.15 m/s. Demyelination can be modeled by decreasing the capacitance and increasing the resistance of the myelin [34]. Two demyelinated neuron models were simulated in this work. The first model had one internode segment demyelinated, and the second model was of three consecutive internode segments. The resulting conduction velocity was calculated for both simulations. For one and three internode segment demyelinated the conduction velocity was slowed to 44.15 m/s, and 27.15 m/s respectively. This model successfully showed that an HH neuron implemented in SPICE could show the effects of demyelination on conduction velocity The goal of this work is to develop a demyelinated neuron so that treatments for Multiple Sclerosis (MS) and other demyelinated neurons could be simulated to test various treatments’ effectiveness. A current treatment for MS is ion channel blockers. Future work would be to use this model to test current ion channel blocker therapy and to validate if such therapies alleviate conduction slowing.

No description available.

Thesis (Ph. D.)--University of Alabama at Birmingham, 2008. / Title from first page of PDF file (viewed Feb 13, 2009). Includes bibliographical references.

O nervo vestíbulo-coclear da cobaia possui peculiaridades não encontradas em outros nervos periféricos. Não foram encontradas informações detalhadas sobre os aspectos morfométricos do VIII nervo craniano em cobaias adultas na literatura. A avaliação descritiva e quantitativa no presente estudo, evidencia informações que precedem o estudo das alterações que ocorrem em modelos experimentais de neuropatias do VIII nervo craniano e as doenças ou lesões que possam afetar o homem. Foram utilizadas 8 cobaias adultas, perfundidas com glutaraldeído a 2,5% em tampão cacodilato de sódio (0,025 M). Seus nervos direito e esquerdo (n=6, 4 nervos direito e 2 esquerdos) foram dissecados na região mediana do nervo e pós fixado com tetróxido de ósmio (OsO4) a 1% e incluídos em resina epóxi Poly/Bed 812®. Os fragmentos foram cortados em secções transversais semifinas seriadas (6 nervos) com uma espessura de 0,5 μm e corados com azul de toluidina para a microscopia de luz. Foram analisados os aspectos histológicos descritivos e topográficos do nervo vestíbulo-coclear em cobaias adultas, bem como os aspectos histométricos na parte mediana do nervo, no referente a densidade de fibras mielínicas, a distribuição dos diâmetros de tal tipo de fibras mielínicas, ao cálculo da razão G e o número de vasos sangüíneos encontrados dentro da área de cada nervo. O nervo coclear é envolvido pelo vestibular na porção inicial da junção de ambos. O conjunto, nervos coclear e vestibular e nervo vestíbulo-coclear têm a aparência bifurcada da letra Y, na horizontal com os ramos lateralizados, possuindo em média 5 mm de comprimento. É ricamente vascularizado e documenta uma completa interposição das fibras dos nervos coclear e vestibular, quando o fascículo do VIII nervo está completamente constituído. As suas fibras mielínicas dispõem-se paralelamente em seu sentido longitudinal e são circundadas por escasso tecido endoneural. Não foram evidencias fibras amielínicas no VIII nervo. A distribuição das fibras mielínicas no segmento mediano do VIII nervo craniano foi unimodal, havendo predomínio de fibras com 3,5 m de diâmetro. O número de fibras foi de 5.390 ± 1.504 fibras. O diâmetro das fibras variou de 1,5 a 6 m de diâmetro. Os axônios com 2,5 m de diâmetro foram predominantes quantitativamente: 6.757 ± 1.922 axônios. O diâmetro axonal variou entre 1 a 4,5 m. A densidade média das fibras do VIII nervo em seu segmento mediano foi de 41.474 ± 4384 fibras/mm2. O diâmetro fascicular foi de 0,77 ± 0,04 mm. A razão G varia de 0,2 a 0,9. O maior número de fibras tem razão G de 0,7 e 0,6, respectivamente, predominando as fibras com 0,7. Os resultados descritos neste trabalho científico são originais, contendo alguns resultados inéditos e pouco estudados na literatura científica sobre a anatomia e morfometria do VIII nervo craniano em cobaia. O nervo vestíbulo-coclear da cobaia é um nervo sensitivo aferente especial, e bem diferente em sua anátomo-fisiologia de todos os outros nervos sensitivos e motores encontrados nos mamíferos. A cobaia adulta é um excelente modelo experimental para o estudo do nervo vestíbulo-coclear, semelhantes aos de humanos. / The vestibulocochlear (VIIIth cranial nerve) nerve of guinea pigs have special features not common for peripheral nerves in general. There are no detailed reports on the morphometric characteristics of the VIII nerve in adult guinea pigs. This is a descriptive and qualitative study that shows normal parameters that are useful in experimental models of the VIIIth nerve neuropathy. Eight adult guinea pigs were perfused with 2.5% glutaraldehyde in isotonic cacodilate buffer (0.025M). The right (N=4) and left (N=2) nerves were dissected in the median region, post-fixed in 1% osmuin tetroxide and embedded in epoxy resin. Semithin (0.5 µm) serial transverse sections were stained with 1% toluidine blue for light microscopy study. The descriptive histology and the topographical and histometric aspects of the median region of the nerve were analyzed, including myelinated fiber density, myelinated fiber diameter distribution, g ratio and number of endoneural capillary vessels. The cochlear nerve is enveloped by the vestibular nerve when they join together. Both, the cochlear and the vestibular nerves join to form the vestibulocochlear nerve with a Y shape, with approximately 5 mm in length. The nerve is widely vascularized and presents a complete mixture of the vestibular and cochlear myelinated fibers when the VIII nerve fascicle is constituted. The myelinated fibers are longitudinally oriented and present few endoneural connective tissue in between. No unmyelinated fibers were evidenced in the VIII nerve. The myelinated fiber diameter distribution was unimodal, with a peak at 3.5, and intervals between 1,5 and 6 m. The average number of fibers was 5.390 ± 1.504. The myelinated axon diameter distribution was also unimodal, with a peak at 2.5 µm of diameter were predominant quantitatively: 6.757 ± 1.922, and intervals between 1 and 4.5 µm. The average myelinated fiber density was 41.474 ± 4384 mm2, spread in a fascicular diameter of 0.77 ± 0.04 mm. The g ratio values varied from 0.2 to 0.9 and most of the myelinated fibers showed g ratio values of 0.7. Our results are original and only few parameters studied here were described in the literature. The vestibulocochlear nerve of the guinea pigs is a special afferent nerve, differing from other peripheral nerves (sensitive and motor) in its main anatomic and physiological characteristics, compared to other nerves from mammals. The adult guinea pig is an excellent model for the vestibulocochlear nerve neuropathy studies once it is similar to the human nerve.

O nervo vestíbulo-coclear da cobaia possui peculiaridades não encontradas em outros nervos periféricos. Não foram encontradas informações detalhadas sobre os aspectos morfométricos do VIII nervo craniano em cobaias adultas na literatura. A avaliação descritiva e quantitativa no presente estudo, evidencia informações que precedem o estudo das alterações que ocorrem em modelos experimentais de neuropatias do VIII nervo craniano e as doenças ou lesões que possam afetar o homem. Foram utilizadas 8 cobaias adultas, perfundidas com glutaraldeído a 2,5% em tampão cacodilato de sódio (0,025 M). Seus nervos direito e esquerdo (n=6, 4 nervos direito e 2 esquerdos) foram dissecados na região mediana do nervo e pós fixado com tetróxido de ósmio (OsO4) a 1% e incluídos em resina epóxi Poly/Bed 812®. Os fragmentos foram cortados em secções transversais semifinas seriadas (6 nervos) com uma espessura de 0,5 μm e corados com azul de toluidina para a microscopia de luz. Foram analisados os aspectos histológicos descritivos e topográficos do nervo vestíbulo-coclear em cobaias adultas, bem como os aspectos histométricos na parte mediana do nervo, no referente a densidade de fibras mielínicas, a distribuição dos diâmetros de tal tipo de fibras mielínicas, ao cálculo da razão G e o número de vasos sangüíneos encontrados dentro da área de cada nervo. O nervo coclear é envolvido pelo vestibular na porção inicial da junção de ambos. O conjunto, nervos coclear e vestibular e nervo vestíbulo-coclear têm a aparência bifurcada da letra Y, na horizontal com os ramos lateralizados, possuindo em média 5 mm de comprimento. É ricamente vascularizado e documenta uma completa interposição das fibras dos nervos coclear e vestibular, quando o fascículo do VIII nervo está completamente constituído. As suas fibras mielínicas dispõem-se paralelamente em seu sentido longitudinal e são circundadas por escasso tecido endoneural. Não foram evidencias fibras amielínicas no VIII nervo. A distribuição das fibras mielínicas no segmento mediano do VIII nervo craniano foi unimodal, havendo predomínio de fibras com 3,5 m de diâmetro. O número de fibras foi de 5.390 ± 1.504 fibras. O diâmetro das fibras variou de 1,5 a 6 m de diâmetro. Os axônios com 2,5 m de diâmetro foram predominantes quantitativamente: 6.757 ± 1.922 axônios. O diâmetro axonal variou entre 1 a 4,5 m. A densidade média das fibras do VIII nervo em seu segmento mediano foi de 41.474 ± 4384 fibras/mm2. O diâmetro fascicular foi de 0,77 ± 0,04 mm. A razão G varia de 0,2 a 0,9. O maior número de fibras tem razão G de 0,7 e 0,6, respectivamente, predominando as fibras com 0,7. Os resultados descritos neste trabalho científico são originais, contendo alguns resultados inéditos e pouco estudados na literatura científica sobre a anatomia e morfometria do VIII nervo craniano em cobaia. O nervo vestíbulo-coclear da cobaia é um nervo sensitivo aferente especial, e bem diferente em sua anátomo-fisiologia de todos os outros nervos sensitivos e motores encontrados nos mamíferos. A cobaia adulta é um excelente modelo experimental para o estudo do nervo vestíbulo-coclear, semelhantes aos de humanos. / The vestibulocochlear (VIIIth cranial nerve) nerve of guinea pigs have special features not common for peripheral nerves in general. There are no detailed reports on the morphometric characteristics of the VIII nerve in adult guinea pigs. This is a descriptive and qualitative study that shows normal parameters that are useful in experimental models of the VIIIth nerve neuropathy. Eight adult guinea pigs were perfused with 2.5% glutaraldehyde in isotonic cacodilate buffer (0.025M). The right (N=4) and left (N=2) nerves were dissected in the median region, post-fixed in 1% osmuin tetroxide and embedded in epoxy resin. Semithin (0.5 µm) serial transverse sections were stained with 1% toluidine blue for light microscopy study. The descriptive histology and the topographical and histometric aspects of the median region of the nerve were analyzed, including myelinated fiber density, myelinated fiber diameter distribution, g ratio and number of endoneural capillary vessels. The cochlear nerve is enveloped by the vestibular nerve when they join together. Both, the cochlear and the vestibular nerves join to form the vestibulocochlear nerve with a Y shape, with approximately 5 mm in length. The nerve is widely vascularized and presents a complete mixture of the vestibular and cochlear myelinated fibers when the VIII nerve fascicle is constituted. The myelinated fibers are longitudinally oriented and present few endoneural connective tissue in between. No unmyelinated fibers were evidenced in the VIII nerve. The myelinated fiber diameter distribution was unimodal, with a peak at 3.5, and intervals between 1,5 and 6 m. The average number of fibers was 5.390 ± 1.504. The myelinated axon diameter distribution was also unimodal, with a peak at 2.5 µm of diameter were predominant quantitatively: 6.757 ± 1.922, and intervals between 1 and 4.5 µm. The average myelinated fiber density was 41.474 ± 4384 mm2, spread in a fascicular diameter of 0.77 ± 0.04 mm. The g ratio values varied from 0.2 to 0.9 and most of the myelinated fibers showed g ratio values of 0.7. Our results are original and only few parameters studied here were described in the literature. The vestibulocochlear nerve of the guinea pigs is a special afferent nerve, differing from other peripheral nerves (sensitive and motor) in its main anatomic and physiological characteristics, compared to other nerves from mammals. The adult guinea pig is an excellent model for the vestibulocochlear nerve neuropathy studies once it is similar to the human nerve.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2010. / Härtill 6 uppsatser.