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Mild traumatic brain injury (mTBI) accounts for approximately 75% of all TBI cases, and the mechanisms are still poorly understood, in part due to limitations of current diagnostic tools. Yet, there is a critical need to detect the presence of mTBI to mitigate risk of further injury. In this study, we explore the potential of collagen hybridizing peptides (CHPs), which selectively bind to damaged collagen, to detect damage in the pia-arachnoid complex (PAC), a major load-transferring interface during head trauma. To generate damage, porcine PAC samples underwent peel tests. Peak force to failure and CHP fluorescence were measured in three regions of the brain at multiple post-mortem times. The peak force of PAC failure was region-specific, with increasing failure forces moving anterior to posterior (frontal: 20.91 ± 38.77 mN; parietal: 64.72 ± 33.31 mN; occipital: 86.68 ± 43.46 mN) and significantly different between frontal and occipital regions (p = 0.034). CHP fluorescence was significantly different between control and peeled PAC samples in mean pixel intensity (MPI; p = 0.031), median pixel intensity (MedPI; p = 0.009), and percent pixels above a defined threshold (PP; p = 0.014). Each of these CHP fluorescence metrics were significantly and positively correlated with peak force at failure (MPI: p = 0.049; MedPI: p = 0.026; PP: p = 0.002). These data suggest CHP is a viable solution to detecting the presence and severity of damage at the brain-skull interface, and may be a useful tool for quantifying damage in vivo.
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Ex-vivo quantification of ovine pia arachnoid complex biomechanical properties under uniaxial tension
Abstract Background The pia arachnoid complex (PAC) is a cerebrospinal fluid-filled tissue conglomerate that surrounds the brain and spinal cord. Pia mater adheres directly to the surface of the brain while the arachnoid mater adheres to the deep surface of the dura mater. Collagen fibers, known as subarachnoid trabeculae (SAT) fibers, and microvascular structure lie intermediately to the pia and arachnoid meninges. Due to its structural role, alterations to the biomechanical properties of the PAC may change surface stress loading in traumatic brain injury (TBI) caused by sub-concussive hits. The aim of this study was to quantify the mechanical and morphological properties of ovine PAC. Methods Ovine brain samples (n = 10) were removed from the skull and tissue was harvested within 30 min post-mortem. To access the PAC, ovine skulls were split medially from the occipital region down the nasal bone on the superior and inferior aspects of the skull. A template was used to remove arachnoid samples from the left and right sides of the frontal and occipital regions of the brain. 10 ex-vivo samples were tested with uniaxial tension at 2 mm s −1 , average strain rate of 0.59 s −1 , until failure at < 5 h post extraction. The force and displacement data were acquired at 100 Hz. PAC tissue collagen fiber microstructure was characterized using second-harmonic generation (SHG) imaging on a subset of n = 4 stained tissue samples. To differentiate transverse blood vessels from SAT by visualization of cell nuclei and endothelial cells, samples were stained with DAPI and anti-von Willebrand Factor, respectively. The Mooney-Rivlin model for average stress–strain curve fit was used to model PAC material properties. Results The elastic modulus, ultimate stress, and ultimate strain were found to be 7.7 ± 3.0, 2.7 ± 0.76 MPa, and 0.60 ± 0.13, respectively. No statistical significance was found across brain dissection locations in terms of biomechanical properties. SHG images were post-processed to obtain average SAT fiber intersection density, concentration, porosity, tortuosity, segment length, orientation, radial counts, and diameter as 0.23, 26.14, 73.86%, 1.07 ± 0.28, 17.33 ± 15.25 µm, 84.66 ± 49.18°, 8.15%, 3.46 ± 1.62 µm, respectively. Conclusion For the sizes, strain, and strain rates tested, our results suggest that ovine PAC mechanical behavior is isotropic, and that the Mooney-Rivlin model is an appropriate curve-fitting constitutive equation for obtaining material parameters of PAC tissues.
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- Award ID(s):
- 1656450
- PAR ID:
- 10273995
- Date Published:
- Journal Name:
- Fluids and Barriers of the CNS
- Volume:
- 17
- Issue:
- 1
- ISSN:
- 2045-8118
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1186/s12987-020-00229-w
