Computerized biomechanical simulation of cerebrospinal fluid hydrodynamics: Challenges and opportunities

Because it lacks a lymphatic circulation, the brain must clear extracellular proteins by an alternative mechanism. The cerebrospinal fluid (CSF) functions as a sink for brain extracellular solutes, but it is not clear how solutes from the brain interstitium move from the parenchyma to the CSF. We demonstrate that a substantial portion of subarachnoid CSF cycles through the brain interstitial space. On the basis of in vivo two-photon imaging of small fluorescent tracers, we showed that CSF enters the parenchyma along paravascular spaces that surround penetrating arteries and that brain interstitial fluid is cleared along paravenous drainage pathways. Animals lacking the water channel aquaporin-4 (AQP4) in astrocytes exhibit slowed CSF influx through this system and a ~70% reduction in interstitial solute clearance, suggesting that the bulk fluid flow between these anatomical influx and efflux routes is supported by astrocytic water transport. Fluorescent-tagged amyloid β, a peptide thought to be pathogenic in Alzheimer's disease, was transported along this route, and deletion of the Aqp4 gene suppressed the clearance of soluble amyloid β, suggesting that this pathway may remove amyloid β from the central nervous system. Clearance through paravenous flow may also regulate extracellular levels of proteins involved with neurodegenerative conditions, its impairment perhaps contributing to the mis-accumulation of soluble proteins.

Mechanical characterization of brain tissue at high loading velocities is crucial for modeling Traumatic Brain Injury (TBI). During severe impact conditions, brain tissue experiences compression, tension and shear. Limited experimental data is available for brain tissue in extension at dynamic strain rates. In this research, a High Rate Tension Device (HRTD) was developed to obtain dynamic properties of brain tissue in extension at strain rates of ≤90/s. In vitro tensile tests were performed to obtain properties of brain tissue at strain rates of 30, 60 and 90/s up to 30% strain. The brain tissue showed a stiffer response with increasing strain rates, showing that hyperelastic models are not adequate. Specifically, the tensile engineering stress at 30% strain was 3.1±0.49kPa, 4.3±0.86kPa, 6.5±0.76kPa (mean±SD) at strain rates of 30, 60 and 90/s, respectively. Force relaxation tests in tension were also conducted at different strain magnitudes (10-60% strain) with the average rise time of 24ms, which were used to derive time dependent parameters. One-term Ogden, Fung and Gent models were used to obtain material parameters from the experimental data. Numerical simulations were performed using a one-term Ogden model to analyze hyperelastic behavior of brain tissue up to 30% strain. The material parameters obtained in this study will help to develop biofidelic human brain finite element models, which can subsequently be used to predict brain injuries under impact conditions and as a reconstruction and simulation tool for forensic investigations. Copyright © 2012 Elsevier Ltd. All rights reserved.