Much concern exists over the role of blast-induced traumatic brain injury (TBI) in the chronic cognitive and mental health problems that develop in veterans and active duty military personnel. The brain vasculature is particularly sensitive to blast injury. The aim of this study was to characterize the evolving molecular and histologic alterations in the neurovascular unit induced by three repetitive low-energy blast exposures (3 × 74.5 kPa) in a rat model mimicking human mild TBI or subclinical blast exposure. High-resolution two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry of purified brain vascular fractions from blast-exposed animals 6 weeks post-exposure showed decreased levels of vascular-associated glial fibrillary acidic protein (GFAP) and several neuronal intermediate filament proteins (α-internexin and the low, middle, and high molecular weight neurofilament subunits). Loss of these proteins suggested that blast exposure disrupts gliovascular and neurovascular interactions. Electron microscopy confirmed blast-induced effects on perivascular astrocytes including swelling and degeneration of astrocytic endfeet in the brain cortical vasculature. Because the astrocyte is a major sensor of neuronal activity and regulator of cerebral blood flow, structural disruption of gliovascular integrity within the neurovascular unit should impair cerebral autoregulation. Disrupted neurovascular connections to pial and parenchymal blood vessels might also affect brain circulation. Blast exposures also induced structural and functional alterations in the arterial smooth muscle layer. Interestingly, by 8 months after blast exposure, GFAP and neuronal intermediate filament expression had recovered to control levels in isolated brain vascular fractions. However, despite this recovery, a widespread vascular pathology was still apparent at 10 months after blast exposure histologically and on micro-computed tomography scanning. Thus, low-level blast exposure disrupts gliovascular and neurovascular connections while inducing a chronic vascular pathology.

Bone mass, architecture, and tissue mineral density contribute to bone strength. As body mass (BM) increases any one or combination of these properties could change to maintain structural integrity. To better understand the structural origins of vertebral fragility and gain insight into the mechanisms that govern bone adaptation, we conducted an integrative analysis of bone mass and microarchitecture in the last lumbar vertebral body from nine strepsirhine species, ranging in size from 42 g (Microcebus rufus) to 2,440 g (Eulemur macaco). Bone mass and architecture were assessed via mCT for the whole body and spherical volumes of interest (VOI). Allometric equations were estimated and compared with predictions for geometric scaling, assuming axial compression as the dominant loading regime. Bone mass, microarchitectural, and vertebral body geometric variables predominantly scaled isometrically. Among structural variables, the degree of anisotropy (Tb.DA) was the only parameter independent of BM and other trabecular architectural variables. Tb.DA was related to positional behavior. Orthograde primates had higher average Tb.DA (1.60) and more craniocaudally oriented trabeculae while lorisines had the lowest Tb.DA (1.25), as well as variably oriented trabeculae. Finally, lorisines had the highest ratio of trabecular bone volume to cortical shell volume ($3x) and while there appears to be flexibility in this ratio, the total bone volume (trabecular þ cortical) scales isometrically (BM 1.23 , r 2 ¼ 0.93) and appears tightly constrained. The common pattern of isometry in our measurements leaves open the question of how vertebral bodies in strepsirhine species compensate for increased BM. Anat Rec,

The accurate measurement of tissue mineral density, ρm, in specimens of unequal size or quantities of bone mineral using polychromatic μCT systems is important, since studies often compare samples with a range of sizes and bone densities. We assessed the influence of object size on μCT measurements of ρm using (1) hydroxyapatite rods (HA), (2) precision-manufactured aluminum foams (AL) simulating trabecular bone structure, and (3) bovine cortical bone cubes (BCt). Two beam-hardening correction (BHC) algorithms, determined using a 200 and 1200 mg/cm3 HA wedge phantom, were used to calculate ρm of the HA and BCt. The 200 mg/cm3 and an aluminum BHC algorithm were used to calculate the linear attenuation coefficients of the AL foams. Equivalent ρm measurements of 500, 1000, and 1500 mg HA/cm3 rods decreased (r2> 0.96, p< 0.05 for all) as HA rod diameter increased in the 200 mg/cm3 BHC data. Errors averaged 8.2% across these samples and reached as high as 29.5%. Regression analyses suggested no size effects in the 1200 mg/cm3 BHC data but differences between successive sizes still reached as high as 13%. The linear attenuation coefficients of the AL foams increased up to approximately 6% with increasing volume fractions (r2> 0.81, p< 0.05 for all) but the strength of the size-related error was also BHC dependent. Equivalent ρm values were inversely correlated with BCt cube size (r2> 0.92, p< 0.05). Use of the 1200 mg/cm3 BHC ameliorated the size-related artifact compared to the 200 mg/cm3 BHC but errors with this BHC were still significant and ranged between 5% and 12%. These results demonstrate that object size, structure, and BHC algorithm can influence μCT measurements of ρm. Measurements of ρm of specimens of unequal size or quantities of bone mineral must be interpreted with caution unless appropriate steps are taken to minimize these potential artifacts.

Background Biomechanical models are commonly used to estimate loads on the spine. Current models have focused on understanding the etiology of low back pain and have not included thoracic vertebral levels. Using experimental data on the stiffness of the thoracic spine, ribcage, and sternum, we developed a new quasi-static stiffness-based biomechanical model to calculate loads on the thoracic and lumbar spine during bending or lifting tasks. Methods To assess the sensitivity of the model to our key assumptions, we determined the effect of varying ribcage and sternal stiffness, maximum muscle stress, and objective function on predicted spinal loads. We compared estimates of spinal loading obtained with our model to previously reported in vivo intradiscal pressures and muscle activation patterns. Findings Inclusion of the ribs and sternum caused an average decrease in vertebral compressive force of 33% for forward flexion and 18% in a lateral moment task. The impact of maximum muscle stress on vertebral force was limited to a narrow range of values. Compressive forces predicted by our model were strongly correlated to in vivo intradiscal pressure measurements in the thoracic (r=0.95) and lumbar (r=1) spine. Predicted trunk muscle activity was also strongly correlated (r=0.95) with previously published EMG data from the lumbar spine. Interpretation The consistency and accuracy of the model predictions appear to be sufficient to justify the use of this model for investigating the relationships between applied loads and injury to the thoracic spine during quasi-static loading activities.

Musculoskeletal modeling requires information on muscle parameters such as cross-sectional area (CSA) and moment arms. A variety of previous studies have reported muscle parameters in the trunk based on in vivo imaging, but there remain gaps in the available data as well as limitations in the generalizability of such data. Specifically, available trunk muscle CSA data is very limited for older adults, lacking entirely in the thoracic region. In addition, previous studies have made measurements in groups of healthy volunteers or hospital patients who may not be representative of the population in general. Finally, such studies have not reported data for the major muscles connecting the upper limb to the thoracic trunk. In this study, muscle morphology measurements were made for major muscles present in the trunk between vertebral levels T6 and L5 using quantitative computed tomography scans from a community-based sample of 100 men and women aged 36–87. We present regression equations to predict trunk muscle CSA and position relative to the vertebral body in the transverse plane from sex, age, height and weight at vertebral levels T6 to L5. Regressions were also developed for predicting anatomical CSA and muscle moment arms, which were estimated using literature data on muscle line of action. This work thus provides a resource for estimating muscle parameters in the general population for musculoskeletal modeling of the thoraco-lumbar trunk.

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To explore the possible mechanisms underlying sex-specific differences in skeletal fragility that may be obscured by two-dimensional areal bone mineral density (aBMD) measures, we compared quantitative computed tomography (QCT)-based vertebral bone measures among pairs of men and women from the Framingham Heart Study Multidetector Computed Tomography Study who were matched for age and spine aBMD. Measurements included vertebral body cross-sectional area (CSA, cm2), trabecular volumetric BMD (Tb.vBMD, g/cm3), integral volumetric BMD (Int.vBMD, g/cm3), estimated vertebral compressive loading and strength (Newtons) at L3, the factor-of-risk (load-to-strength ratio), and vertebral fracture prevalence. We identified 981 male-female pairs (1:1 matching) matched on age (± 1 year) and QCT-derived aBMD of L3 (± 1%), with an average age of 51 years (range 34 to 81 years). Matched for aBMD and age, men had 20% larger vertebral CSA, lower Int.vBMD (−8%) and Tb.vBMD (−9%), 10% greater vertebral compressive strength, 24% greater vertebral compressive loading, and 12% greater factor-of-risk than women (p < 0.0001 for all), as well as higher prevalence of vertebral fracture. After adjusting for height and weight, the differences in CSA and volumetric bone mineral density (vBMD) between men and women were attenuated but remained significant, whereas compressive strength was no longer different. In conclusion, vertebral size, morphology, and density differ significantly between men and women matched for age and spine aBMD, suggesting that men and women attain the same aBMD by different mechanisms. These results provide novel information regarding sex-specific differences in mechanisms that underlie vertebral fragility.

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