Mild traumatic brain injury (mTBI) induced by low-intensity blast (LIB) is a serious health problem affecting military service members and veterans. Our previous reports using a single open-field LIB mouse model showed the absence of gross microscopic damage or necrosis in the brain, while transmission electron microscopy (TEM) identified ultrastructural abnormalities of myelin sheaths, mitochondria, and synapses. The neurovascular unit (NVU), an anatomical and functional system with multiple components, is vital for the regulation of cerebral blood flow and cellular interactions. In this study, we delineated ultrastructural abnormalities affecting the NVU in mice with LIB exposure quantitatively and qualitatively. Luminal constrictive irregularities were identified at 7 days post-injury (DPI) followed by dilation at 30 DPI along with degeneration of pericytes. Quantitative proteomic analysis identified significantly altered vasomotor-related proteins at 24 h post-injury. Endothelial cell, basement membrane and astrocyte end-foot swellings, as well as vacuole formations, occurred in LIB-exposed mice, indicating cellular edema. Structural abnormalities of tight junctions and astrocyte end-foot detachment from basement membranes were also noted. These ultrastructural findings demonstrate that LIB induces multiple-component NVU damage. Prevention of NVU damage may aid in identifying therapeutic targets to mitigate the effects of primary brain blast injury.

Blast-induced neurotrauma (BINT) is a pressing concern for veterans and civilians exposed to explosive devices. Affected personnel may have increased risk for long-term cognitive decline and developing tauopathies including Alzheimer’s disease-related disorders (ADRD) or frontal-temporal dementia (FTD). The goal of this study was to identify the effect of BINT on molecular networks and their modulation by mutant tau in transgenic (Tg) mice overexpressing the human tau P301L mutation (rTg4510) linked to FTD or non-carriers. The primary focus was on the phosphoproteome because of the prominent role of hyperphosphorylation in neurological disorders. Discrimination learning was assessed following injury in the subsequent 6 weeks, using the automated home-cage monitoring CognitionWall platform. At 40 days post injury, label-free phosphoproteomics was used to evaluate molecular networks in the frontal cortex of mice. Utilizing a weighted peptide co-expression network analysis (WpCNA) approach, we identified phosphopeptide networks tied to associative learning and mossy-fiber pathways and those which predicted learning outcomes. Phosphorylation levels in these networks were inversely related to learning and linked to synaptic dysfunction, cognitive decline, and dementia including Atp6v1a and Itsn1. Low-intensity blast (LIB) selectively increased pSer262tau in rTg4510, a site implicated in initiating tauopathy. Additionally, individual and group level analyses identified the Arhgap33 phosphopeptide as an indicator of BINT-induced cognitive impairment predominantly in rTg4510 mice. This study unveils novel interactions between ADRD genetic susceptibility, BINT, and cognitive decline, thus identifying dysregulated pathways as targets in potential precision-medicine focused therapeutics to alleviate the disease burden among those affected by BINT.

The role of convection in liquid thermoelectric cells may be difficult to predict because the inter- and intramolecular interactions are not currently incorporated into thermodynamic models. Here, we study the thermoelectric response of a series of five anhydrous 1-methyl-3- alkylimidazolium halide ionic liquids with varied chain length and counterion in a high-aspect-ratio, horizontal-temperature-gradient geometry, where convection is minimal. While a canonical constant-volume thermodynamic model predicts that the longer aliphatic groups exhibit larger Seebeck coefficients, we instead measure the opposite: Longer aliphatic chains correlate with lower densities and greater heat expansion, stronger intermolecular associations, stronger steric repulsion, and lower Seebeck coefficients. As evidence of the critical role of thermal expansion, we measure that the Seebeck effect is nonlinear: Values of −2.8 mV/K with a 10 K temperature difference and −1.8 mV/K with a 50 K difference are measured with ether ion. Our results indicate that steric repulsion and heat expansion are important considerations in ionic liquid design; with large temperature differences, the Seebeck coefficient correlates negatively with heat expansion. Our results suggest that Seebeck values will improve if thermal expansion is limited in a pressurized, isochoric, convection-free design.

Background: Temporalis muscle (TM) atrophy is a commonly encountered cosmesis issue following craniotomies. This retrospective study aims to investigate the correlation of clinical and surgical factors with postoperative TM volume and head symmetry in patients undergoing frontotemporal craniotomy. Methods: Medical records were retrospectively reviewed for patients undergoing pterional or middle fossa craniotomy. Pre- and post-operative clinical factors, intraoperative factors, and magnetic resonance imaging magnetic resonance imaging scans were obtained. TM volumes (cm³) were measured using volumetric analysis. 3-D reconstructed images of the head were independently reviewed to grade head symmetry on a binary scale. Pairwise correlation matrix, multiple linear regression (MLR), and logistic regression (LR) were used to assess the relationship of clinical and operative factors with TM volume and head symmetry. Results: A total of 46 patients were included for analysis, including pterional (n = 27) and middle fossa (n = 19) groups. The average TM volume loss was 36.8% (standard deviation [Std]: 17.18%) and 29.5% (Std: 16.72%) for patients receiving pterional and middle fossa craniotomies, respectively, indicating the pterional approach may carry a greater risk of disrupting the TM neurovascular supply ensuing subsequent cosmetic disfigurement. MLR identified age and scalp thickness as predictors of TM volume (P < 0.05). Age and scalp thickness were also the only factors found to be predictors of head asymmetry (P < 0.01). Conclusion: Pterional and middle fossa craniotomy procedures are both associated with significant TM volume loss and subsequent head asymmetry. Age and preoperative scalp thickness are independent risk factors for the development of TM volume loss and head asymmetry. These findings could contribute to the development of preoperative risk stratification algorithms, enabling neurosurgeons to predict the likelihood of cosmetic disfigurement. This would enhance preoperative counseling for patients undergoing craniotomy procedures, especially for elderly individuals and those with thin scalps. Overall, this study provides valuable insights into prognostic factors that may impact the development of poor cosmesis following frontotemporal craniotomy.