ROLE OF OLFACTORY RECEPTOR78 IN CAROTID BODY DEPENDENT SYMPATHETIC ACTIVATION AND HYPERTENSION IN MURINE MODELS OF CHRONIC INTERMITTENT HYPOXIA

Chronic intermittent hypoxia (CIH) is a hallmark manifestation of obstructive sleep apnea (OSA), a widespread breathing disorder. CIH treated rodents exhibit activation of the sympathetic nervous system and hypertension. Heightened carotid body (CB) activity has been implicated in CIH-induced hypertension. CB expresses high abundance of olfactory receptor (Olfr) 78, a G-protein coupled receptor. Olfr 78 null mice exhibit impaired CB sensory nerve response to acute hypoxia. Present study examined whether Olfr78 participates in CB-dependent activation of the sympathetic nervous system and hypertension in CIH treated mice and in hemeoxygenase (HO)-2 null mice experiencing CIH as a consequence of naturally occurring OSA. CIH treated wild type (WT) mice showed hypertension, bio-markers of sympathetic nerve activation, and enhanced CB sensory nerve response to hypoxia and sensory long-term facilitation (sLTF), and these responses were absent in CIH treated Olfr78 null mice. HO-2 null mice showed higher apnea index (AI) (58±1.2 apneas/hour) than WT mice (AI= 8±0.8 apneas/hour), and exhibited elevated blood pressure (BP), plasma NE levels and heightened CB sensory nerve response to hypoxia and sLTF. The magnitude of hypertension correlated with AI in HO-2 null mice. In contrast, HO-2/Olfr78 double null mice showed absence of elevated BP, plasma NE levels, augmented CB response to hypoxia and sLTF. These results demonstrate that Olfr78 participates in sympathetic nerve activation and hypertension, and heightened CB activity in two murine models of CIH.

Nerve Response to Superelastic Shape Memory Polyurethane Aerogels

We have previously shown the suitability of aerogels as scaffolds for neuronal cells. Here, we report on the use of superelastic shape memory polyurethane aerogels (SSMPA). SSMPA have a distinctly different stiffness than previously reported aerogels. The soft and deformable nature of SSMPA allowed for radial compression of the aerogel induced by a custom designed apparatus. This radial compression changed the pore diameter and surface roughness (Sa) of SSMPA, while maintaining similar stiffness. Two varieties of SSMPA were used, Mix-14 and Mix-18, with distinctly different pore diameters and Sa. Radial compression led to a decreased pore diameter, which, in turn, decreased the Sa. The use of custom designed apparatus and two types of SSMPA allowed us to examine the influence of stiffness, pore size, and Sa on the extension of processes (neurites) by PC12 neuronal cells. PC12 cells plated on SSMPA with a higher degree of radial compression extended fewer neurites per cell when compared to other groups. However, the average length of the neurites was significantly longer when compared to the unrestricted group and to those extended by cells plated on SSMPA with less radial compression. These results demonstrate that SSMPA with 1.9 µm pore diameter, 1.17 µm Sa, and 203 kPa stiffness provides the optimum combination of physical parameters for nerve regeneration.

A Quantitative Investigation on the Peripheral Nerve Response within the Small Strain Range

Peripheral nerves are very complex biological structures crucial to linking the central nervous system to the periphery of the body. However, their real behaviour is partially unknown because of the intrinsic difficulty of studying these structures in vivo. As a consequence, theoretical and computational tools together with in vitro experiments are widely used to approximate the mechanical response of the peripheral nervous tissue to different kind of solicitations. More specifically, particular conditions narrow the mechanical response of peripheral nerves within the small strain regime. Therefore, in this work, the mechanical response of nerves was investigated through the study of the relationships among strain, stress and displacements within the small strain range. Theoretical predictions were quantitatively compared to experimental evidences, while the displacement field was studied for different values of the tissue compressibility. This framework provided a straightforward computational assessment of the nerve response, which was needed to design suitable connections to biomaterials or neural interfaces within the small strain range.