Gleason, Rudy | Search NASA

NASA NTRS2016

Characterization of the Biomechanical Behavior of the Optic Nerve Sheath

A major priority in current space medicine research is to characterize the mechanisms in Visual Impairment and Intracranial Pressure (VIIP) syndrome, a group of ophthalmic changes that occur in some astronauts following long-duration spaceflight [1]. It is hypothesized that microgravity-induced cephalad fluid shifts lead to increases in intracranial pressure (ICP), which drives maladaptive remodeling of the optic nerve sheath (ONS). In this study, we investigated the effects of mechanical loading on the porcine ONS to better understand the mechanical response of the ONS to increased ICP.

fluid shift (biological)↗

NASA NTRS2016

Optic Nerve Sheath Mechanics in VIIP Syndrome

Visual Impairment Intracranial Pressure (VIIP) syndrome is a major concern in current space medicine research. While the exact pathology of VIIP is not yet known, it is hypothesized that the microgravity-induced cephalad fluid shift increases intracranial pressure (ICP) and drives remodeling of the optic nerve sheath. To investigate this possibility, we are culturing optic nerve sheath dura mater samples under different pressures and investigating changes in tissue composition. To interpret results from this work, it is essential to first understand the biomechanical response of the optic nerve sheath dura mater to loading. Here, we investigated the effects of mechanical loading on the porcine optic nerve sheath.Porcine optic nerves (number: 6) were obtained immediately after death from a local abattoir. The optic nerve sheath (dura mater) was isolated from the optic nerve proper, leaving a hollow cylinder of connective tissue that was used for biomechanical characterization. We developed a custom mechanical testing system that allowed for unconfined lengthening, twisting, and circumferential distension of the dura mater during inflation and under fixed axial loading. To determine the effects of variations in ICP, the sample was inflated (0-60 millimeters Hg) and circumferential distension was simultaneously recorded. These tests were performed under variable axial loads (0.6 grams - 5.6 grams at increments of 1 gram) by attaching different weights to one end of the dura mater. Results and Conclusions: The samples demonstrated nonlinear behavior, similar to other soft connective tissue (Figure 1). Large increases in diameter were observed at lower transmural pressures (approximately 0 to 5 millimeters Hg), whereas only small diameter changes were observed at higher pressures. Particularly interesting was the existence of a cross-over point at a pressure of approximately 11 millimeters Hg. At this pressure, the same diameter is obtained for all axial loads applied to the tissue; i.e., as the axial load is varied, the diameter of the dura mater remains constant. This cross-over in the pressure-diameter curves occurred in all optic nerve sheaths that were tested, and may correspond with in vivo ICP levels for pigs. These data suggest that diameter of the dura mater of the optic nerve remains nearly constant in vivo despite being stretched axially. This may be a homeostatic mechanism aimed at maintaining target stresses/strains on the cells in the dura mater, and deviations from these stresses may play an important role in optic nerve sheath remodeling. Future studies will involve subjecting the dura mater to varying pressures and axial tensions for extended periods of time, while monitoring changes in the biomechanical properties. The data can then be used to study the effects of changes in ICP on the remodeling of the dura mater.

biomechanics↗

NASA NTRS2015

Optic Nerve Sheath Mechanics in VIIP Syndrome

Visual Impairment and Intracranial Pressure (VIIP) syndrome results in a loss of visual function and occurs in astronauts following long-duration spaceflight. Understanding the mechanisms that lead to the ocular changes involved in VIIP is of critical importance for space medicine research. Although the exact mechanisms of VIIP are not yet known, it is hypothesized that microgravity-induced increases in intracranial pressures (ICP) drive the remodeling of the optic nerve sheath, leading to compression of the optic nerve which in turn may reduce visual acuity. Some astronauts present with a kink in the optic nerve after return to earth, suggesting that tissue remodeling in response to ICP increases may be taking place. The goal of this work is to characterize the mechanical properties of the optic nerve sheath (dura mater) to better understand its biomechanical response to increased ICP.

microgravity↗

NASA NTRS2015

VIIP: Central Nervous System (CNS) Modeling

Current long-duration missions to the International Space Station and future exploration-class missions beyond low-Earth orbit expose astronauts to increased risk of Visual Impairment and Intracranial Pressure (VIIP) syndrome. It has been hypothesized that the headward shift of cerebrospinal fluid (CSF) and blood in microgravity may cause significant elevation of intracranial pressure (ICP), which in turn may then induce VIIP syndrome through interaction with various biomechanical pathways. However, there is insufficient evidence to confirm this hypothesis. In this light, we are developing lumped-parameter models of fluid transport in the central nervous system (CNS) as a means to simulate the influence of microgravity on ICP. The CNS models will also be used in concert with the lumped parameter and finite element models of the eye described in the related IWS works submitted by Nelson et al., Feola et al. and Ethier et al.

intraocular pressure↗

NASA NTRS2014

Biomechanics of the Optic Nerve Sheath in VIIP Syndrome

Long-duration space flight carries the risk of developing Visual Impairment and Intracranial Pressure (VIIP) syndrome, a spectrum of ophthalmic changes including posterior globe flattening, choroidal folds, distension of the optic nerve sheath (ONS), optic nerve kinking and potentially permanent degradation of visual function. The slow onset of VIIP, its chronic nature, and certain clinical features strongly suggest that biomechanical factors acting on the ONS play a role in VIIP. Here we measure several relevant ONS properties needed to model VIIP biomechanics. The ONS (meninges) of fresh porcine eyes (n7) was reflected, the nerve proper was truncated near the sclera, and the meninges were repositioned to create a hollow cylinder of meningeal connective tissue attached to the posterior sclera. The distal end was cannulated, sealed, and pressure clamped (mimicking cerebrospinal fluid [CSF] pressure), while the eye was also cannulated for independent control of intraocular pressure (IOP). The meninges were inflated (CSF pressure cycling 7-50 mmHg) while ONS outer diameter was imaged. In another set of experiments (n4), fluid permeation rate across the meninges was recorded by observing the drainage of an elevated fluid reservoir (30 mmHg) connected to the meninges. The ONS showed behavior typical of soft tissues: viscoelasticity, with hysteresis in early preconditioning cycles and repeatable behavior after 4 cycles, and nonlinear stiffening, particularly at CSF pressures 15 mmHg (Figure). Tangent moduli measured from the loading curve were 372 101, 1199 358, and 2050 379 kPa (mean SEM) at CSF pressures of 7, 15 and 30 mmHg, respectively. Flow rate measurements through the intact meninges at 30mmHg gave a permeability of 1.34 0.46 lmincm2mmHg (mean SEM). The ONS is a tough, strain-stiffening connective tissue that is surprisingly permeable. The latter observation suggests that there could be significant CSF drainage through the ONS into the orbit, likely important for CSF transport in the optic nerve. These experimental measurements, extended to human eyes, are informing computational models of the pathophysiology and biomechanics of the ONS in VIIP syndrome.

fluid shifts↗

NASA NTRS2014

Optic Nerve Sheath Mechanics and Permeability in VIIP Syndrome

Long-duration space flight carries the risk of developing Visual Impairment and Intracranial Pressure (VIIP) syndrome, a spectrum of ophthalmic changes including posterior globe flattening, choroidal folds, distension of the optic nerve sheath (ONS), optic nerve kinking and potentially permanent degradation of visual function. The slow onset of VIIP, its chronic nature, and certain clinical features strongly suggest that biomechanical factors acting on the ONS play a role in VIIP. Here we measure several relevant ONS properties needed to model VIIP biomechanics. The ONS (meninges) of fresh porcine eyes (n7) was reflected, the nerve proper was truncated near the sclera, and the meninges were repositioned to create a hollow cylinder of meningeal connective tissue attached to the posterior sclera. The distal end was cannulated, sealed, and pressure clamped (mimicking cerebrospinal fluid [CSF] pressure), while the eye was also cannulated for independent control of intraocular pressure (IOP). The meninges were inflated (CSF pressure cycling 7-50 mmHg) while ONS outer diameter was imaged. In another set of experiments (n4), fluid permeation rate across the meninges was recorded by observing the drainage of an elevated fluid reservoir (30 mmHg) connected to the meninges. The ONS showed behavior typical of soft tissues: viscoelasticity, with hysteresis in early preconditioning cycles and repeatable behavior after 4 cycles, and nonlinear stiffening, particularly at CSF pressures 15 mmHg (Figure). Tangent moduli measured from the loading curve were 372 101, 1199 358, and 2050 379 kPa (mean SEM) at CSF pressures of 7, 15 and 30 mmHg, respectively. Flow rate measurements through the intact meninges at 30mmHg gave a permeability of 1.34 0.46 lmincm2mmHg (mean SEM). The ONS is a tough, strain-stiffening connective tissue that is surprisingly permeable. The latter observation suggests that there could be significant CSF drainage through the ONS into the orbit, likely important for CSF transport in the optic nerve. These experimental measurements, extended to human eyes, are informing computational models of the pathophysiology and biomechanics of the ONS in VIIP syndrome.

biomechanics↗