Pre-Clinical Traumatic Brain Injury Common Data Elements: Toward a Common Language Across Laboratories

Smith, Douglas H.; Hicks, Ramona; Johnson, Victoria E.; Bergstrom, Debra A.; Cummings, Diana M.; Noble, Linda; Hovda, David A.; Whalen, Michael J.; Ahlers, Stephen T.; LaPlaca, Michelle C.; Tortella, Frank C.; Duhaime, Ann Christine; Dixon, C. Edward

doi:10.1089/neu.2014.3861

Cited by 88 publications

(83 citation statements)

References 128 publications

(120 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For other regions of the body, a more complete description of the loading condition eventually led to scaling laws that allowed one to transfer these from the laboratory to the scenario in theater and vice versa , and helped develop protective equipment (Bass et al, 2008; Bowen et al, 1968). To date, there is no such consensus on how to report experimental blast conditions for models of bTBI, although there is now an agreement for developing common preclinical data elements in TBI models (Smith et al, 2015) and these more extensive loading conditions should be considered part of the archived information. In addition to the parameters of loading these should include both the direction of the propagating wave, orientation of the head, and possible reloading from multiple reflections of the shockwave.…”

Section: Discussionmentioning

confidence: 99%

Primary blast injury causes cognitive impairments and hippocampal circuit alterations

Beamer¹,

Tummala²,

Gullotti³

et al. 2016

Experimental Neurology

View full text Add to dashboard Cite

Blast-induced traumatic brain injury (bTBI) and its long term consequences are a major health concern among veterans. Despite recent work enhancing our knowledge about bTBI, very little is known about the contribution of the blast wave alone to the observed sequelae. Herein, we isolated its contribution in a mouse model by constraining the animals' heads during exposure to a shockwave (primary blast). Our results show that exposure to primary blast alone results in changes in hippocampus-dependent behaviors that correspond with electro-physiological changes in area CA1 and are accompanied by reactive gliosis. Specifically, five days after exposure, behavior in an open field and performance in a spatial object recognition (SOR) task were significantly different from sham. Network electrophysiology, also performed five days after injury, demonstrated a significant decrease in excitability and increase in inhibitory tone. Immunohistochemistry for GFAP and Iba1 performed ten days after injury showed a significant increase in staining. Interestingly, a threefold increase in the impulse of the primary blast wave did not exacerbate these measures. However, we observed a significant reduction in the contribution of the NMDA receptors to the field EPSP at the highest blast exposure level. Our results emphasize the need to account for the effects of primary blast loading when studying the sequelae of bTBI.

show abstract

Section: Discussionmentioning

confidence: 99%

Primary blast injury causes cognitive impairments and hippocampal circuit alterations

Beamer¹,

Tummala²,

Gullotti³

et al. 2016

Experimental Neurology

View full text Add to dashboard Cite

show abstract

“…These studies indicate that depending upon the imaging methods and extravasating dyes used, the severity and extent of BBB disruption is differential depending upon the size of the molecule. This calls for a standardization and optimization of detection parameters and techniques [63]. …”

Section: Blood–brain Barrier Disruption After Stroke and Traumatic Brmentioning

confidence: 99%

Blood−brain barrier breakdown and neovascularization processes after stroke and traumatic brain injury

Prakash

Carmichael²

2015

Current Opinion in Neurology

246

171

View full text Add to dashboard Cite

Purpose of review Angiogenesis or vascular reorganization plays a role in recovery after stroke and traumatic brain injury (TBI). In this review, we have focused on two major events that occur during stroke and TBI from a vascular perspective – what is the process and time course of blood–brain barrier (BBB) breakdown? and how does the surrounding vasculature recover and facilitate repair? Recent findings Despite differences in the primary injury, the BBB changes overlap between stroke and TBI. Disruption of BBB involves a series of events: formation of caveolae, trans and paracellular disruption, tight junction breakdown and vascular disruption. Confounding factors that need careful assessment and standardization are the severity, duration and extent of the stroke and TBI that influences BBB disruption. Vascular repair proceeds through long-term neovascularization processes: angiogenesis, arteriogenesis and vasculogenesis. Enhancing each of these processes may impart beneficial effects in endogenous recovery. Summary Our understanding of BBB breakdown acutely after the cerebrovascular injury has come a long way; however, we lack a clear understanding of the course of BBB disruption and BBB recovery and the evolution of individual cellular events associated with BBB change. Neovascularization responses have been widely studied in stroke for their role in functional recovery but the role of vascular reorganization after TBI in recovery is much less defined.

show abstract

“…Unfortunately, despite reports of hundreds of treatments that have show efficacy in rodent models of TBI, none have translated to clinical use despite over 30 clinical trials based on the preclinical data [47, 48]. While the lack of positive findings in clinical studies may reflect the complexity and heterogeneity of human TBI and challenges in clinical trial design [28], it may also serve as a cautionary tale of the inability of rodent models to replicate the pathophysiology and neurodegenerative sequelae of clinical TBI [49]. …”

Section: Introductionmentioning

confidence: 99%

A Porcine Model of Traumatic Brain Injury via Head Rotational Acceleration

Cullen

Harris

Browne

et al. 2016

Methods in Molecular Biology

Self Cite

102

104

View full text Add to dashboard Cite

Unique from other brain disorders, traumatic brain injury (TBI) generally results from a discrete biomechanical event that induces rapid head movement. The large size and high organization of the human brain makes it particularly vulnerable to traumatic injury from rotational accelerations that can cause dynamic deformation of the brain tissue. Therefore, replicating the injury biomechanics of human TBI in animal models presents a substantial challenge, particularly with regard to addressing brain size and injury parameters. Here we present the historical development and use of a porcine model of head rotational acceleration. By scaling up the rotational forces to account for difference in brain mass between swine and humans, this model has been shown to produce the same tissue deformations and identical neuropathologies found in human TBI. The parameters of scaled rapid angular accelerations applied for the model reproduce inertial forces generated when the human head suddenly accelerates or decelerates in falls, collisions, or blunt impacts. The model uses custom-built linkage assemblies and a powerful linear actuator designed to produce purely impulsive nonimpact head rotation in different angular planes at controlled rotational acceleration levels. Through a range of head rotational kinematics, this model can produce functional and neuropathological changes across the spectrum from concussion to severe TBI. Notably, however, the model is very difficult to employ, requiring a highly skilled team for medical management, biomechanics, neurological recovery, and specialized outcome measures including neuromonitoring, neurophysiology, neuroimaging, and neuropathology. Nonetheless, while challenging, this clinically relevant model has proven valuable for identifying mechanisms of acute and progressive neuropathologies as well as for the evaluation of noninvasive diagnostic techniques and potential neuroprotective treatments following TBI.

show abstract

Pre-Clinical Traumatic Brain Injury Common Data Elements: Toward a Common Language Across Laboratories

Cited by 88 publications

References 128 publications

Primary blast injury causes cognitive impairments and hippocampal circuit alterations

Primary blast injury causes cognitive impairments and hippocampal circuit alterations

Blood−brain barrier breakdown and neovascularization processes after stroke and traumatic brain injury

A Porcine Model of Traumatic Brain Injury via Head Rotational Acceleration

Contact Info

Product

Resources

About