Neurological disease in boxers.

Behavioral, axonal, and proteomic alterations following repeated mild traumatic brain injury: Novel insights using a clinically relevant rat model.

Abstract Image segmentation remains the most critical step in Digital Rock Physics (DRP) workflows, affecting the analysis of physical rock properties. Conventional segmentation techniques struggle with numerous image artifacts and user bias, which lead to considerable uncertainty. This study evaluates the advantages of using the random forest (RF) algorithm for the segmentation of fractured rocks. The segmentation quality is discussed and compared with two conventional image processing methods (thresholding-based and watershed algorithm) and an encoder–decoder network in the form of convolutional neural networks (CNNs). The segmented images of the RF method were used as the ground truth for CNN training. The images of two fractured rock samples are acquired by X-ray computed tomography scanning (XCT). The skeletonized 3D images are calculated, providing information about the mean mechanical aperture and roughness. The porosity, permeability, flow fields, and preferred flow paths of segmented images are analyzed by the DRP approach. Moreover, the breakthrough curves obtained from tracer injection experiments are used as ground truth to evaluate the segmentation quality of each method. The results show that the conventional methods overestimate the fracture aperture. Both machine learning approaches show promising segmentation results and handle all artifacts and complexities without any prior CT-image filtering. However, the RF implementation has superior inherent advantages over CNN. This method is resource-saving (e.g., quickly trained), does not need an extensive training dataset, and can provide the segmentation uncertainty as a measure for evaluating the segmentation quality. The considerable variation in computed rock properties highlights the importance of choosing an appropriate segmentation method. 

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Benchmarking conventional and machine learning segmentation techniques for digital rock physics analysis of fractured rocks

It is increasingly reported that a history of concussion may be associated with chronic deleterious consequences. While the pathophysiology that contributes to these consequences is not well understood, neuroinflammation is postulated to be critical. Activation of multi-protein complexes termed inflammasomes, a key component of this inflammatory response, has been reported in more severe TBIs; however, it has not been investigated in milder TBIs, such as concussion. This study investigated serum levels of interleukin (IL)-1β and IL-18 (key proteins activated downstream of these inflammasomes) at acute, sub-acute, and chronic time-points post-concussion. We recruited 105 Australian footballers (65 male, 40 female) during the pre-season, then prospectively followed these players for the occurrence of concussion during the season. At baseline, 58 footballers reported a previous concussion history, and 47 reported no previous concussion history. Additionally, 25 players sustained a mid-season concussion and were sampled at 2, 6, and 13 days post-concussion. Serum levels of IL-1β and IL-18 were quantified using highly sensitive Simoa HD-X Analyzer assays. At baseline, IL-1β levels were higher in male, but not female, footballers with a previous concussion history compared with footballers with no concussion history. There was also a positive correlation between years of collision sport participation and IL-18 levels in males. No evidence was found in males or females to indicate that IL-1β or IL-18 levels differed at 2, 6, or 13 days post-concussion. These findings provide novel insights into potential sex-specific physiological consequences of concussion, and suggest that neuroinflammation may be persistent chronically following concussion in male athletes.

Elevated Serum Interleukin-1β Levels in Male, but not Female, Collision Sport Athletes with a Concussion History.

A novel preclinical pediatric concussion model causes neurobehavioural impairment and diffuse neurodegeneration

Pannexin 1 (Panx1) is a ubiquitously expressed protein forming large conductance channels that are central to many distinct inflammation and injury responses. There is accumulating evidence showing ATP released from Panx1 channels, as well as metabolites, provide effective paracrine and autocrine signaling molecules that regulate different elements of the injury response. As channels with a broad range of permselectivity, Panx1 channels mediate the secretion and uptake of multiple solutes, ranging from calcium to bacterial derived molecules. In this review, we describe how Panx1 functions in response to different pro-inflammatory stimuli, focusing mainly on signaling coordinated by the vasculature. How Panx1 mediates ATP release by injured cells is also discussed. The ability of Panx1 to serve as a central component of many diverse physiologic responses has proven to be critically dependent on the context of expression, post-translational modification, interacting partners, and the mode of stimulation.

/pdf/pannexin-1-as-a-driver-of-inflammation-and-ischemia-4m20p3cmcq.pdf

Pannexin 1 as a driver of inflammation and ischemia–reperfusion injury

Adolescent brain injuries have devastating impacts on lifelong health given that adolescence is a critical period for brain development. Adolescents are susceptible to mild traumatic brain injuries (mTBIs) acquired from collisions in contact sports, which are often sustained in a repetitive nature (repetitive mild traumatic brain injuries; RmTBIs), and cause compounding, sexually dimorphic neurological deficits. Neuroinflammation accompanies RmTBIs and may be a central driving force for chronic neurological decline. To date, the impact of neuroinflammation and sex-specific dynamics during adolescent RmTBIs has been understudied. A lateral impact model (LIM) was developed that mimics the biomechanical forces commonly experienced in human mTBIs. Here, we report novel sexually dimorphic neurobehavioral and -inflammatory responses using LIM to model adolescent RmTBIs. We first subjected adolescent male C57Bl/6 mice to one, three, or five RmTBIs at 24-h intervals and quantified neurobehavioral deficits, and brain volumetric and structural changes by magnetic resonance imaging. Five RmTBIs caused significant motor deficits, increased brain volume in cortex, hippocampus, and corpus callosum, and reduced white matter integrity in the corpus callosum. We then compared neurobehavioral deficits in adolescent male and female mice and observed sex-specific deficits in motor function, whereas both sexes had dysfunction in learning and memory. Flow cytometric quantification of neuroinflammatory responses revealed time- and sex-dependent infiltration of peripheral macrophages and T cells and male-specific decreases in microglia number. Using immunohistochemistry, we report specific microglia density decreases in male mice in the motor cortex and thalamus. We show novel neuroinflammatory responses after adolescent brain injuries that expands the current understanding of RmTBI pathophysiology in this critical neurodevelopmental period.

Repetitive Mild Traumatic Brain Injuries in Mice during Adolescence Cause Sexually Dimorphic Behavioral Deficits and Neuroinflammatory Dynamics.

While the physical and behavioral symptomologies associated with a single mild traumatic brain injury (mTBI) are typically transient, repetitive mTBIs (RmTBI) have been associated with persisting neurological deficits. Therefore, this study examined the progressive changes in behaviour and the neuropathological outcomes associated with chronic RmTBI through adolescence and adulthood in male and female Sprague Dawley rats. Rats experienced 2 mTBIs/week for 15 weeks, and were periodically tested for changes in motor behaviour, cognitive function, emotional disturbances, and aggression. Brain tissue was examined for neuropathological changes in ventricle size, and presentation of Iba1 and GFAP. We did not see progressively worse behavioral impairments with the accumulation of injuries or time, but did find evidence for neurological and functional change (motor disturbance, reduced exploration, reduced aggression, alteration in depressive-like behaviour, deficits in short-term working memory). Neuropathological assessment of RmTBI animals identified an increase in ventricle size, prolonged changes in GFAP, and sex-differences in Iba1, in the corpus callosum, thalamus, and medial prefrontal cortex. Telomere length reduced exponentially as the injury load increased. Overall, chronic RmTBI did not result in accumulating behavioral impairment and there is a need to further investigate progressive behavioral changes associated with repeated injuries in adolescence and young adulthood.

Thomas Carr

Papers

Pannexin 1 as a driver of inflammation and ischemia–reperfusion injury

Repetitive Mild Traumatic Brain Injuries in Mice during Adolescence Cause Sexually Dimorphic Behavioral Deficits and Neuroinflammatory Dynamics.

Examining the Progressive Behavior and Neuropathological Outcomes Associated with Chronic Repetitive Mild Traumatic Brain Injury in Rats.