Lakiesha N. Williams

Traumatic brain injuries (TBI) present a major public health challenge, demanding an in-depth understanding of age-specific signs and vulnerabilities. Aging not only significantly influences brain function and plasticity but also elevates the risk of hospitalizations and death following repetitive mild traumatic brain injuries (rmTBIs). In this study, we investigate the impact of age on brain network changes and white matter properties following rmTBI employing a multi-modal approach that integrates resting-state functional magnetic resonance imaging (rsfMRI), graph theory analysis, diffusion tensor imaging (DTI), and Neurite Orientation Dispersion and Density Imaging (NODDI). Utilizing the CHIMERA model, we conducted rmTBIs or sham (control) procedures on young (2.5-3 months old) and aged (22-month-old) male and female mice to model high risk groups. Functional and structural imaging unveiled age-related reductions in communication efficiency between brain regions, while injuries induced opposing effects on the small-world index across age groups, influencing network segregation. Functional connectivity analysis also identified alterations in 79 out of 148 brain regions by age, treatment (sham vs. rmTBI), or their interaction. Injuries exerted pronounced effects on sensory integration areas, including insular and motor cortices. Age-related disruptions in white matter integrity were observed, indicating alterations in various diffusion directions (mean, radial, axial diffusivity, fractional anisotropy) and density neurite properties (dispersion index, intracellular and isotropic volume fraction). Inflammation, assessed through Iba-1 and GFAP markers, correlated with higher dispersion in the optic tract, suggesting a neuroinflammatory response in aged animals. These findings provide a comprehensive understanding of the intricate interplay between age, injuries, and brain connectivity, shedding light on the long-term consequences of rmTBIs.

Cerebrospinal fluid (CSF) leakage is a common postoperative complication of neurosurgical procedures, with iatrogenic causes accounting for 16% of CSF leakages. This complication increases healthcare costs and patient morbidity. The focus of this review is to analyze the rates of CSF leakage of some of the most commonly used xenogeneic and synthetic dural substitutes following surgeries in the infratentorial region of the brain where surgical repair can be most challenging. A systematic literature search was conducted using studies detailing duraplasty procedures performed with nonautologous grafts in the infratentorial region in PubMed. Studies were identified using the following search terms: "posterior fossa" or "infratentorial" were used in combination with "CSF leak," "CSF leakage," "cerebrospinal fluid leakage," "duraplasty" or "dura graft." The outcome of interest was a measure of the prevalence of CSF leakage rates following posterior fossa neurosurgery. Studies that contributed data to this review were published between 2006 and 2021. The dural graft materials utilized included: bovine collagen, acellular dermis, equine collagen, bovine pericardium, collagen matrix, and expanded polytetrafluoroethylene (ePTFE). The number of subjects in studies on each of these grafts ranged from 6 to 225. CSF leak rates ranged from 0% to 25% with the predominance of studies reporting between 3% and 15%. The studies that utilize bovine collagen, equine collagen, and acellular dermis reported higher CSF leakage rates; whereas studies that utilized ePTFE, bovine pericardium, and collagen matrix reported lower CSF leakage rates. Due to the heterogeneity of methodologies used across these studies, it is difficult to draw a direct correlation between the dural patch products used and CSF leaks. Larger prospective controlled studies that evaluate various products in a head-to-head fashion, using the same methods and animal models, are needed to conclude the relative efficacy of these dural patch products.

The anterior cruciate ligament plays a major role in maintaining the stability of the knee joint and is susceptible to injury under strenuous activity. Anterior cruciate ligament (ACL) injuries can lead to joint instability and complications such as osteoarthritis. Despite this, there is a lack of material models capable of predicting damage at a localized fiber level, hindering our ability to understand how damage develops in real-time. This work develops a continuum-damage material model of the ACL and applies the model to a finite element simulation of the knee undergoing high quadriceps tendon loading. Using quadriceps tendon loadings of 1000, 1500, and 2000 N, the development of microstructural damage within the ACL tissue was examined, and the effects of localized damage on the joint kinematics were investigated. Damage tended to develop in the midsubstance of the ACL in the present model in the anterior medial bundle region and could induce significant changes in the joint kinematics. Using this model, new insights into the development of ACL injury mechanisms can be investigated.

The anterior cruciate ligament (ACL) plays a pivotal role in support of the knee under loading. When damaged, it is known that substantial changes in the mechanics of the neighboring ligaments can be observed. However, a localized damage approach to investigating how ACL deficiency influences the neighboring ligaments has not been carried out. To do this, a finite element model, incorporating a continuum damage material model of the ACL, was implemented. Localized ACL damage was induced using high quadriceps force loading. Once damaged, anterior shear forces or tibial torque loadings were applied to the knee joint. The relative changes in stress contour and average mid-substance stress were examined for each of the neighboring ligaments following localized ACL damage. It was observed that localized ACL damage could produce notable changes in the mechanics of the neighboring knee ligaments, with non-homogenous stress contour shape changes and average stress magnitude being observed to increase in most cases, with a notable exception occurring in the MCL for both loading modes. In addition, the ligament bearing the most loading also changed with ACL deficiency. These changes carry implications as to morphological effects that may be induced following localized ACL damage, indicating that early diagnosis of ACL injury may be helpful in mitigating other complications post injury.