Neurosteroids and Traumatic Brain Injury: Translating Biomarkers to Therapeutics; Overview and Pilot Investigations in Iraq and Afghanistan Era Veterans

Marx, CE; Naylor, JC; Kilts, JD; Dunn, C E; Tupler, LA; St, Szabo; Capehart, BP; Ra, Morey; Shampine, LJ; Acheson, SK

doi:10.1201/b18959-12

Cited by 5 publications

(3 citation statements)

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“…This is not only because of the higher incidence of milder injuries, but it is now recognized that they can create lasting cognitive disturbances and even reduce the threshold to re‐injury and make the brain more vulnerable to severe pathology if re‐injured . This turning point in recognition of what constitutes TBI in patients is now being explored in preclinical models of mild head injury, enabling research into pathophysiology and preventative management strategies and therapeutic interventions . Perhaps, the links between milder joint injuries and OA similarly require more attention and awareness, and classifying these Type II and III injuries as PTOA models could be an important first step.…”

Section: What Is Post‐traumatic Osteoarthritis (Ptoa)?mentioning

confidence: 99%

Using mouse models to investigate the pathophysiology, treatment, and prevention of post‐traumatic osteoarthritis

Blaker

Clarke

Little

2016

Journal Orthopaedic Research

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Post-traumatic osteoarthritis (PTOA) is defined by its development after joint injury. Factors contributing to the risk of PTOA occurring, the rate of progression, and degree of associated disability in any individual, remain incompletely understood. What constitutes an "OA-inducing injury" is not defined. In line with advances in the traumatic brain injury field, we propose the scope of PTOA-inducing injuries be expanded to include not only those causing immediate structural damage and instability (Type I), but also those without initial instability/damage from moderate (Type II) or minor (Type III) loading severity. A review of the literature revealed this full spectrum of potential PTOA subtypes can be modeled in mice, with 27 Type I, 6 Type II, and 4 Type III models identified. Despite limitations due to cartilage anatomy, joint size, and bio-fluid availability, mice offer advantages as preclinical models to study PTOA, particularly genetically modified strains. Histopathology was the most common disease outcome, cartilage more frequently studied than bone or synovium, and meniscus and ligaments rarely evaluated. Other methods used to examine PTOA included gene expression, protein analysis, and imaging. Despite the major issues reported by patients being pain and biomechanical dysfunction, these were the least commonly measured outcomes in mouse models. Informative correlations of simultaneously measured disease outcomes in individual animals, was rarely done in any mouse PTOA model. This review has identified knowledge gaps that need to be addressed to increase understanding and improve prevention and management of PTOA. Preclinical mouse models play a critical role in these endeavors. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:424-439, 2017.

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Section: What Is Post‐traumatic Osteoarthritis (Ptoa)?mentioning

confidence: 99%

Using mouse models to investigate the pathophysiology, treatment, and prevention of post‐traumatic osteoarthritis

Blaker

Clarke

Little

2016

Journal Orthopaedic Research

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“…Approaches for accomplishing this include reawakening the growth potential of the surviving neurons or antagonizing the inhibition of axonal growth and synaptogenesis. Alternatively, cellular replacement is achievable in certain brain regions that possess nascent neural stem cells [ 25 , 31 , 102 , 103 , 104 ]. Thus, the discussed concept of “traumatic penumbra” imbues the transition between injury and repair at the NVU with profound implications for selecting the appropriate type and timing of neuroprotective interventions.…”

Section: What Are the Roles Of Neurotrophins After Acute Neural Inmentioning

confidence: 99%

Neurotrauma: The Crosstalk between Neurotrophins and Inflammation in the Acutely Injured Brain

Meirelles

Simon

Regner

2017

IJMS

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Traumatic brain injury (TBI) is a major cause of morbidity and mortality among young individuals worldwide. Understanding the pathophysiology of neurotrauma is crucial for the development of more effective therapeutic strategies. After the trauma occurs, immediate neurologic damage is produced by the traumatic forces; this primary injury triggers a secondary wave of biochemical cascades together with metabolic and cellular changes, called secondary neural injury. In the scenario of the acutely injured brain, the ongoing secondary injury results in ischemia and edema culminating in an uncontrollable increase in intracranial pressure. These areas of secondary injury progression, or areas of “traumatic penumbra”, represent crucial targets for therapeutic interventions. Neurotrophins are a class of signaling molecules that promote survival and/or maintenance of neurons. They also stimulate axonal growth, synaptic plasticity, and neurotransmitter synthesis and release. Therefore, this review focuses on the role of neurotrophins in the acute post-injury response. Here, we discuss possible endogenous neuroprotective mechanisms of neurotrophins in the prevailing environment surrounding the injured areas, and highlight the crosstalk between neurotrophins and inflammation with focus on neurovascular unit cells, particularly pericytes. The perspective is that neurotrophins may represent promising targets for research on neuroprotective and neurorestorative processes in the short-term following TBI.

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“…Approaches for accomplishing this include reawakening the growth potential of the surviving neurons or antagonizing the inhibition of axonal growth and synaptogenesis. Alternatively, cellular replacement is achievable in certain brain regions that possess nascent neural stem cells [25,43,[109][110][111]. Thus, the discussed concept of traumatic penumbra imbues the transition between injury and repair at the NVU with profound implications for selecting the appropriate type and timing of neuroprotective interventions [34].…”

Section: Mechanisms Of Neural Injury In the Traumatic Penumbramentioning

confidence: 99%

Traumatic Penumbra: Opportunities for Neuroprotective and Neurorestorative Processes

Regner¹,

Meirelles²,

Simon³

2018

Traumatic Brain Injury - Pathobiology, Advanced Diagnostics and Acute Management

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Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. Understanding the pathophysiology of TBI is crucial for the development of more effective therapeutic strategies. At the moment of the traumatic impact, transfer of kinetic forces causes neurologic damage; this primary injury triggers a secondary wave of biochemical cascades, together with metabolic and cellular changes, called secondary neural injury. These areas of ongoing secondary injury, or areas of "traumatic penumbra," represent crucial targets for therapeutic interventions. This chapter is focused on the interplay between progression of parenchymal injury and the neuroprotective and neurorestorative processes that are emerging and developing subsequently to traumatic impact. Thus, we emphasized the role of traumatic penumbra in TBI pathogenesis and suggested a crucial contribution of the neurovascular units (NVUs) and paracrine effects of exosomes and miRNAs in promoting neurological recovery.

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Neurosteroids and Traumatic Brain Injury: Translating Biomarkers to Therapeutics; Overview and Pilot Investigations in Iraq and Afghanistan Era Veterans

Cited by 5 publications

References 1 publication

Using mouse models to investigate the pathophysiology, treatment, and prevention of post‐traumatic osteoarthritis

Using mouse models to investigate the pathophysiology, treatment, and prevention of post‐traumatic osteoarthritis

Neurotrauma: The Crosstalk between Neurotrophins and Inflammation in the Acutely Injured Brain

Traumatic Penumbra: Opportunities for Neuroprotective and Neurorestorative Processes

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