Electrophysiological white matter dysfunction and association with neurobehavioral deficits following low-level primary blast trauma

Park, Eugene; Eisen, Rebecca J.; Kinio, Anna; Baker, Andrew J.

doi:10.1016/j.nbd.2012.12.002

Cited by 38 publications

(41 citation statements)

References 48 publications

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“…More specifically, whereas the model proposed here accounts for two alteration mechanisms-namely, geometrical deformation and immediate ion channel damagethis experimental work highlights the role of neurofilament expression alteration. After an injury, neurofilaments have been observed to accumulate in the soma, suggesting an alteration of the transport mechanisms in axons and thus changes in axonal caliber (Park et al 2013). As demonstrated by the model proposed here, geometrical deformation of the axon invariably leads to changes in the signal propagation.…”

Section: Damage Time Scalesmentioning

confidence: 57%

“…The lack of protective myelin of the NRs (Shreiber et al 2009), recent findings highlighting the primordial role of blast-damaged ion channels in neurobehavioral deficits (Park et al 2013), and the Na v leak observed during trauma (Wang et al 2009) suggest the need for a strain-based damage criterion specific to the ion channels' properties. This Na v (and in this model, K v ) leak has been rationalized by a hyperpolarizing shift (or left-shift) of transient current operational range (Wang et al 2009) in the conductance of the ion channel.…”

Section: Damage Coupling Modelmentioning

confidence: 99%

“…A similar study focused on long-term (up to 14 days) electrophysiological dysfunctions after blast trauma has highlighted the need for the consideration of another time scale (Park et al 2013). More specifically, whereas the model proposed here accounts for two alteration mechanisms-namely, geometrical deformation and immediate ion channel damagethis experimental work highlights the role of neurofilament expression alteration.…”

Section: Damage Time Scalesmentioning

confidence: 99%

“…Additionally, axonal injury has been shown to lead to cleavage of all-spectrin (a cortical axoplasm protein), either attacked by Ca 2+ proteases, originally overactivated by Na + /Ca 2+ exchangers (Wang et al 2009) overwhelmed by a possible initial Na v leak, or simply mechanically sheared (Park et al 2013). This cleavage then reduces the association of this protein with ankyrin G (a protein involved in the anchoring of Na v channels), thus leading to a diffusion and reorganization of Na v channels at the NRs (Park et al 2013).…”

Section: Damage Time Scalesmentioning

confidence: 99%

“…This cleavage then reduces the association of this protein with ankyrin G (a protein involved in the anchoring of Na v channels), thus leading to a diffusion and reorganization of Na v channels at the NRs (Park et al 2013). Again, such change is suggested to lead to a decrease in AP on a long-term basis.…”

Section: Damage Time Scalesmentioning

confidence: 99%

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A computational model coupling mechanics and electrophysiology in spinal cord injury

Jérusalem

García-Grajales

Merchán-Pérez

et al. 2013

Biomech Model Mechanobiol

174

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Traumatic brain injury and spinal cord injury have recently been put under the spotlight as major causes of death and disability in the developed world. Despite the important ongoing experimental and modeling campaigns aimed at understanding the mechanics of tissue and cell damage typically observed in such events, the differentiated roles of strain, stress and their corresponding loading rates on the damage level itself remain unclear. More specifically, the direct relations between brain and spinal cord tissue or cell damage, and electrophysiological functions are still to be unraveled. Whereas mechanical modeling efforts are focusing mainly on stress distribution and mechanisticbased damage criteria, simulated function-based damage criteria are still missing. Here, we propose a new multiscale model of myelinated axon associating electrophysiological impairment to structural damage as a function of strain and strain rate. This multiscale approach provides a new framework for damage evaluation directly relating neuron mechanics and electrophysiological properties, thus providing a link between mechanical trauma and subsequent functional deficits.

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Section: Damage Time Scalesmentioning

confidence: 57%

Section: Damage Coupling Modelmentioning

confidence: 99%

Section: Damage Time Scalesmentioning

confidence: 99%

Section: Damage Time Scalesmentioning

confidence: 99%

Section: Damage Time Scalesmentioning

confidence: 99%

See 3 more Smart Citations

A computational model coupling mechanics and electrophysiology in spinal cord injury

Jérusalem

García-Grajales

Merchán-Pérez

et al. 2013

Biomech Model Mechanobiol

174

View full text Add to dashboard Cite

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Role of Microvascular Disruption in Brain Damage from Traumatic Brain Injury

Logsdon

Lucke‐Wold

Turner

et al. 2015

Comprehensive Physiology

127

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Traumatic brain injury (TBI) is acquired from an external force, which can inflict devastating effects to the brain vasculature and neighboring neuronal cells. Disruption of vasculature is a primary effect that can lead to a host of secondary injury cascades. The primary effects of TBI are rapidly occurring while secondary effects can be activated at later time points and may be more amenable to targeting. Primary effects of TBI include diffuse axonal shearing, changes in blood brain barrier (BBB) permeability, and brain contusions. These mechanical events, especially changes to the BBB, can induce calcium perturbations within brain cells producing secondary effects, which include cellular stress, inflammation, and apoptosis. These secondary effects can be potentially targeted to preserve the tissue surviving the initial impact of TBI. In the past, TBI research had focused on neurons without any regard for glial cells and the cerebrovasculature. Now a greater emphasis is being placed on the vasculature and the neurovascular unit following TBI. A paradigm shift in the importance of the vascular response to injury has opened new avenues of drug treatment strategies for TBI. However, a connection between the vascular response to TBI and the development of chronic disease has yet to be elucidated. Long-term cognitive deficits are common amongst those sustaining severe or multiple mild TBIs. Understanding the mechanisms of cellular responses following TBI is important to prevent the development of neuropsychiatric symptoms. With appropriate intervention following TBI, the vascular network can perhaps be maintained and the cellular repair process possibly improved to aid in the recovery of cellular homeostasis.

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Cellular Mechanisms and Behavioral Outcomes in Blast-Induced Neurotrauma: Comparing Experimental Setups

Bailey

Hubbard

VandeVord

2016

Methods in Molecular Biology

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Blast-induced neurotrauma (BINT) has increased in incidence over the past decades and can result in cognitive issues that have debilitating consequences. The exact primary and secondary mechanisms of injury have not been elucidated and appearance of cellular injury can vary based on many factors, such as blast overpressure magnitude and duration. Many methodologies to study blast neurotrauma have been employed, ranging from open-field explosives to experimental shock tubes for producing free-field blast waves. While there are benefits to the various methods, certain specifications need to be accounted for in order to properly examine BINT. Primary cell injury mechanisms, occurring as a direct result of the blast wave, have been identified in several studies and include cerebral vascular damage, blood-brain barrier disruption, axonal injury, and cytoskeletal damage. Secondary cell injury mechanisms, triggered subsequent to the initial insult, result in the activation of several molecular cascades and can include, but are not limited to, neuroinflammation and oxidative stress. The collective result of these secondary injuries can lead to functional deficits. Behavioral measures examining motor function, anxiety traits, and cognition/memory problems have been utilized to determine the level of injury severity. While cellular injury mechanisms have been identified following blast exposure, the various experimental models present both concurrent and conflicting results. Furthermore, the temporal response and progression of pathology after blast exposure have yet to be detailed and remain unclear due to limited resemblance of methodologies. This chapter summarizes the current state of blast neuropathology and emphasizes the need for a standardized preclinical model of blast neurotrauma.

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Electrophysiological white matter dysfunction and association with neurobehavioral deficits following low-level primary blast trauma

Cited by 38 publications

References 48 publications

A computational model coupling mechanics and electrophysiology in spinal cord injury

A computational model coupling mechanics and electrophysiology in spinal cord injury

Role of Microvascular Disruption in Brain Damage from Traumatic Brain Injury

Cellular Mechanisms and Behavioral Outcomes in Blast-Induced Neurotrauma: Comparing Experimental Setups

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