Diffuse Axonal and Vascular Pathology in the Gyrencephalic Brain after High-Energy Blunt Injury: Clinicopathological Correlations Involving the Brainstem.

Traumatic brain injury (TBI) after high-energy, behind helmet blunt trauma (BHBT) is an important but poorly understood clinical entity often associated with apnea and death in humans. In this study, we use a swine model of high-energy BHBT to characterize key neuropathologies and their association with acute respiratory decompensation. Animals with either stable or critical vital signs were euthanized within 4 h after injury for neuropathological assessment, with emphasis on axonal and vascular pathologies in the brainstem.

Accelerated Aging after Traumatic Brain Injury: An ENIGMA Multi-Cohort Mega-Analysis.

Objective: The long-term consequences of traumatic brain injury (TBI) on brain structure remain uncertain. Given evidence that a single significant brain injury event increases the risk of dementia, brain-age estimation could provide a novel and efficient indexing of the long-term consequences of TBI. Brain-age procedures use predictive modeling to calculate brain-age scores for an individual using structural magnetic resonance imaging (MRI) data.

Dynamic strain fields of the mouse brain during rotation.

Mouse models are used to better understand brain injury mechanisms in humans, yet there is a limited understanding of biomechanical relevance, beginning with how the murine brain deforms when the head undergoes rapid rotation from blunt impact. This problem makes it difficult to translate some aspects of diffuse axonal injury from mouse to human. To address this gap, we present the two-dimensional strain field of the mouse brain undergoing dynamic rotation in the sagittal plane.

NAD, Axonal Maintenance, and Neurological Disease.

The remarkable geometry of the axon exposes it to unique challenges for survival and maintenance. Axonal degeneration is a feature of peripheral neuropathies, glaucoma, and traumatic brain injury, and an early event in neurodegenerative diseases. Since the discovery of Wallerian degeneration (WD), a molecular program that hijacks nicotinamide adenine dinucleotide (NAD) metabolism for axonal self-destruction, the complex roles of NAD in axonal viability and disease have become research priority.

Traumatic Axonal Injury in the Optic Nerve: The Selective Role of SARM1 in the Evolution of Distal Axonopathy.

Traumatic axonal injury (TAI), thought to be caused by rotational acceleration of the head, is a prevalent neuropathology in traumatic brain injury (TBI). TAI in the optic nerve is a common finding in multiple blunt-force TBI models and hence a great model to study mechanisms and treatments for TAI, especially in view of the compartmentalized anatomy of the visual system. We have previously shown that the somata and the proximal, but not distal, axons of retinal ganglion cells (RGC) respond to DLK/LZK blockade after impact acceleration of the head (IA-TBI).

Traumatic axonopathy in spinal tracts after impact acceleration head injury: Ultrastructural observations and evidence of SARM1-dependent axonal degeneration.

Traumatic axonal injury (TAI) and the associated axonopathy are common consequences of traumatic brain injury (TBI) and contribute to significant neurological morbidity. It has been previously suggested that TAI activates a highly conserved program of axonal self-destruction known as Wallerian degeneration (WD). In the present study, we utilize our well-established impact acceleration model of TBI (IA-TBI) to characterize the pathology of injured myelinated axons in the white matter tracks traversing the ventral, lateral, and dorsal spinal columns in the mouse and assess the effect of Sterile Alpha and TIR Motif Containing 1 (Sarm1) gene knockout on acute and subacute axonal degeneration and myelin pathology.

Long-Term Changes in Axon Calibers after Injury: Observations on the Mouse Corticospinal Tract.

White matter pathology is common across a wide spectrum of neurological diseases. Characterizing this pathology is important for both a mechanistic understanding of neurological diseases as well as for the development of neuroimaging biomarkers. Although axonal calibers can vary by orders of magnitude, they are tightly regulated and related to neuronal function, and changes in axon calibers have been reported in several diseases and their models.

Protective effects of NAMPT or MAPK inhibitors and NaR on Wallerian degeneration of mammalian axons.

Wallerian degeneration (WD) is a conserved axonal self-destruction program implicated in several neurological diseases. WD is driven by the degradation of the NAD synthesizing enzyme NMNAT2, the buildup of its substrate NMN, and the activation of the NAD degrading SARM1, eventually leading to axonal fragmentation. The regulation and amenability of these events to therapeutic interventions remain unclear.

Toward a global and reproducible science for brain imaging in neurotrauma: the ENIGMA adult moderate/severe traumatic brain injury working group.

The global burden of mortality and morbidity caused by traumatic brain injury (TBI) is significant, and the heterogeneity of TBI patients and the relatively small sample sizes of most current neuroimaging studies is a major challenge for scientific advances and clinical translation. The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Adult moderate/severe TBI (AMS-TBI) working group aims to be a driving force for new discoveries in AMS-TBI by providing researchers world-wide with an effective framework and platform for large-scale cross-border collaboration and data sharing. Based on the principles of transparency, rigor, reproducibility and collaboration, we will facilitate the development and dissemination of multiscale and big data analysis pipelines for harmonized analyses in AMS-TBI using structural and functional neuroimaging in combination with non-imaging biomarkers, genetics, as well as clinical and behavioral measures.

The Behavioral Neuroscience of Traumatic Brain Injury.

Traumatic brain injury is a calamity of various causes, pathologies, and extremely varied and often complex clinical presentations. Because of its predilection for brain systems underlying cognitive and complex behavioral operations, it may cause chronic and severe psychiatric illness that requires expert management. This is more so for the modern epidemic of athletic and military brain injuries which are dominated by psychiatric symptoms.

Update on the Neuropsychiatry of Substance Use Disorders.

This article reviews some of the recent discoveries about how neurobiological processes contribute to the understanding and treatment of substance use disorders. Particular focus is given to cannabis, opioids, and designer drugs. Important areas addressed include triggers and cravings, the central roles of dopamine and stress, and the endocannabinoid system.

Neuropsychiatry: Definitions, Concepts, and Patient Types.

Neuropsychiatry is an integrative discipline defined by its history, its preferred patients, and its theoretic framework. Dealing with human behavior needs to consider the brain, but such consideration should avoid oversimplification: neurologic understanding is not essential, necessary, or desirable in all conditions encountered in clinical psychiatry. Neuropsychiatric theory is founded on discoveries in the areas of synaptic plasticity and cortical/limbic anatomy (bottom-up), but also evolutionary biology and anthropology (top-down).

Targeted disruption of dual leucine zipper kinase and leucine zipper kinase promotes neuronal survival in a model of diffuse traumatic brain injury.

Background: Traumatic brain injury (TBI) is a major cause of CNS neurodegeneration and has no disease-altering therapies. It is commonly associated with a specific type of biomechanical disruption of the axon called traumatic axonal injury (TAI), which often leads to axonal and sometimes perikaryal degeneration of CNS neurons. We have previously used genome-scale, arrayed RNA interference-based screens in primary mouse retinal ganglion cells (RGCs) to identify a pair of related kinases, dual leucine zipper kinase (DLK) and leucine zipper kinase (LZK) that are key mediators of cell death in response to simple axotomy.

Optogenetically transduced human ES cell-derived neural progenitors and their neuronal progenies: Phenotypic characterization and responses to optical stimulation.

Optogenetically engineered human neural progenitors (hNPs) are viewed as promising tools in regenerative neuroscience because they allow the testing of the ability of hNPs to integrate within nervous system of an appropriate host not only structurally, but also functionally based on the responses of their differentiated progenies to light. Here, we transduced H9 embryonic stem cell-derived hNPs with a lentivirus harboring human channelrhodopsin (hChR2) and differentiated them into a forebrain lineage. We extensively characterized the fate and optogenetic functionality of hChR2-hNPs in vitro with electrophysiology and immunocytochemistry.

Wallerian degeneration as a therapeutic target in traumatic brain injury.

Purpose Of Review: Diffuse or traumatic axonal injury is one of the principal pathologies encountered in traumatic brain injury (TBI) and the resulting axonal loss, disconnection, and brain atrophy contribute significantly to clinical morbidity and disability. The seminal discovery of the slow Wallerian degeneration mice (Wld) in which transected axons do not degenerate but survive and function independently for weeks has transformed concepts on axonal biology and raised hopes that axonopathies may be amenable to specific therapeutic interventions. Here we review mechanisms of axonal degeneration and also describe how these mechanisms may inform biological therapies of traumatic axonopathy in the context of TBI.

Primary Traumatic Axonopathy in Mice Subjected to Impact Acceleration: A Reappraisal of Pathology and Mechanisms with High-Resolution Anatomical Methods.

Traumatic axonal injury (TAI) is a common neuropathology in traumatic brain injury and is featured by primary injury to axons. Here, we generated TAI with impact acceleration of the head in male transgenic mice in which specific populations of neurons and their axons are labeled with yellow fluorescent protein. This model results in axonal lesions in multiple axonal tracts along with blood-brain barrier disruption and neuroinflammation.

Preclinical modelling of militarily relevant traumatic brain injuries: Challenges and recommendations for future directions.

As a follow-up to the 2008 state-of-the-art (SOTA) conference on traumatic brain injuries (TBIs), the 2015 event organized by the United States Department of Veterans Affairs (VA) Office of Research and Development (ORD) analysed the knowledge gained over the last 7 years as it relates to basic scientific methods, experimental findings, diagnosis, therapy, and rehabilitation of TBIs and blast-induced neurotraumas (BINTs). The current article summarizes the discussions and recommendations of the scientific panel attending the Preclinical Modeling and Therapeutic Development Workshop of the conference, with special emphasis on factors slowing research progress and recommendations for ways of addressing the most significant pitfalls.

Task-based statistical image reconstruction for high-quality cone-beam CT.

Task-based analysis of medical imaging performance underlies many ongoing efforts in the development of new imaging systems. In statistical image reconstruction, regularization is often formulated in terms to encourage smoothness and/or sharpness (e.g.

Enhancing oligodendrocyte differentiation by transient transcription activation via DNA nanoparticle-mediated transfection.

Unlabelled: Current approaches to derive oligodendrocytes from human pluripotent stem cells (hPSCs) need extended exposure of hPSCs to growth factors and small molecules, which limits their clinical application because of the lengthy culture time required and low generation efficiency of myelinating oligodendrocytes. Compared to extrinsic growth factors and molecules, oligodendrocyte differentiation and maturation can be more effectively modulated by regulation of the cell transcription network. In the developing central nervous system (CNS), two basic helix-loop-helix transcription factors, Olig1 and Olig2, are decisive in oligodendrocyte differentiation and maturation.

Multi-resolution statistical image reconstruction for mitigation of truncation effects: application to cone-beam CT of the head.

A prototype cone-beam CT (CBCT) head scanner featuring model-based iterative reconstruction (MBIR) has been recently developed and demonstrated the potential for reliable detection of acute intracranial hemorrhage (ICH), which is vital to diagnosis of traumatic brain injury and hemorrhagic stroke. However, data truncation (e.g.

Patient Profiles of Criminal Behavior in the Context of Traumatic Brain Injury.

Traumatic brain injury (TBI) can lead to significant post-traumatic disturbances in mood and behavior, with the frontal lobes playing a key role in emotional and behavioral regulation. Injury to the frontal lobe can result in disinhibition and aggression which can result in police intervention and/or incarceration. We highlight four adult cases with a history of severe TBI with frontal lobe injuries and the presence of post-TBI criminal behaviors.

Clinicopathological correlates of depression in early Alzheimer's disease in the NACC.

Objective: Depression may be a prodrome to Alzheimer's disease (AD). We assessed whether AD neuropathology is associated with depression in mild cognitive impairment (MCI) and mild dementia (dAD).

Methods: All clinical and neuropathological data for this study came from the National Alzheimer's Coordinating Center (NACC).