Animal models of sports‐related head injury: bridging the gap between pre‐clinical research and clinical reality

“…141,149 A more detailed review of functional deficits and brain pathology after TBI created by impact or weight drop on a closed skull has been provided by others. 8,122,150 While having several advantages over the open skull and whole animal blast models discussed above, in most weight-drop and impactor models, head acceleration also makes a considerable contribution to the injury, as discussed below. Moreover, in contrast to typical weight-drop and impactor models, the skin remains intact in our model, which may make the action of the concussive forces more true to those causing TBI in humans, and also mitigate the possibility of skull fracture.…”

Section: Comparison With Blast Models In Rodentsmentioning

confidence: 99%

A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice

Guley

Rogers

Mar

et al. 2016

Journal of Neurotrauma

104

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Mild traumatic brain injury (TBI) from focal head impact is the most common form of TBI in humans. Animal models, however, typically use direct impact to the exposed dura or skull, or blast to the entire head. We present a detailed characterization of a novel overpressure blast system to create focal closed-head mild TBI in mice. A high-pressure air pulse limited to a 7.5 mm diameter area on the left side of the head overlying the forebrain is delivered to anesthetized mice. The mouse eyes and ears are shielded, and its head and body are cushioned to minimize movement. This approach creates mild TBI by a pressure wave that acts on the brain, with minimal accompanying head acceleration-deceleration. A single 20-psi blast yields no functional deficits or brain injury, while a single 25-40 psi blast yields only slight motor deficits and brain damage. By contrast, a single 50-60 psi blast produces significant visual, motor, and neuropsychiatric impairments and axonal damage and microglial activation in major fiber tracts, but no contusive brain injury. This model thus reproduces the widespread axonal injury and functional impairments characteristic of closed-head mild TBI, without the complications of systemic or ocular blast effects or head acceleration that typically occur in other blast or impact models of closed-skull mild TBI. Accordingly, our model provides a simple way to examine the biomechanics, pathophysiology, and functional deficits that result from TBI and can serve as a reliable platform for testing therapies that reduce brain pathology and deficits.

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“…Helicon Focus software version 3.2 (HeliconSoft, Kharkov, Ukraine) was used for three-dimensional reconstruction of z section thickness. The total number of Iba-1epositive cells was expressed per mm 2 . Bushy microglial cells were identified by short thick processes, few branches, and larger cell body volume.…”

Section: Quantitative and Densitometry Analysismentioning

confidence: 99%

“…mTBI has been extensively modeled in mice and rats. 2 Most of these rodent models use fewer than five mTBIs, and report adverse events, including intracerebral bleeding, skull fractures, severe axonal injury, neuronal cell death, and increased mortality. 3e8 These adverse events prevent the scaling up of these animal models to reproduce the highly repetitive mTBI seen in impact sports.…”

mentioning

confidence: 99%

Dendritic Spine Loss and Chronic White Matter Inflammation in a Mouse Model of Highly Repetitive Head Trauma

Winston

Noël

Neustadtl

et al. 2016

The American Journal of Pathology

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Mild traumatic brain injury (mTBI) is an emerging risk for chronic behavioral, cognitive, and neurodegenerative conditions. Athletes absorb several hundred mTBIs each year; however, rodent models of repeat mTBI (rmTBI) are often limited to impacts in the single digits. Herein, we describe the effects of 30 rmTBIs, examining structural and pathological changes in mice up to 365 days after injury. We found that single mTBI causes a brief loss of consciousness and a transient reduction in dendritic spines, reflecting a loss of excitatory synapses. Single mTBI does not cause axonal injury, neuroinflammation, or cell death in the gray or white matter. Thirty rmTBIs with a 1-day interval between each mTBI do not cause dendritic spine loss; however, when the interinjury interval is increased to 7 days, dendritic spine loss is reinstated. Thirty rmTBIs cause white matter pathology characterized by positive silver and Fluoro-Jade B staining, and microglial proliferation and activation. This pathology continues to develop through 60 days, and is still apparent at 365 days, after injury. However, rmTBIs did not increase b-amyloid levels or tau phosphorylation in the 3xTg-AD mouse model of Alzheimer disease. Our data reveal that single mTBI causes a transient loss of synapses, but that rmTBIs habituate to repetitive injury within a short time period. rmTBI causes the development of progressive white matter pathology that continues for months after the final impact. (Am J Pathol 2016, 186: 552e567; http://dx.doi.org/ 10.1016/j.ajpath.2015 Athletes participating in contact sports are at high risk of exposure to large numbers of concussive and subconcussive mild traumatic brain injuries (mTBIs). Recent studies using head impact telemetry systems have begun to reveal how many head impacts an individual football player can receive in the process of playing his or her sport. In a study of high school football players, the number of helmet impacts >20 g recorded in a single season ranged from a low of 226 (average, 4.7 per session) to a high of 1855 (average, 38.6 per session). 1 Most of these impacts do not result in the clinical diagnosis of a concussion; however, it is not known if the cumulative effects of these impacts can result in increased damage to the brain. mTBI has been extensively modeled in mice and rats. 2 Most of these rodent models use fewer than five mTBIs, and report adverse events, including intracerebral bleeding, skull fractures, severe axonal injury, neuronal cell death, and increased mortality.

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Animal models of sports‐related head injury: bridging the gap between pre‐clinical research and clinical reality

Cited by 50 publications

References 134 publications

Introductory Chapter: Introduction to Update in Amyotrophic Lateral Sclerosis and Review of this Condition in Sportsmen

Introductory Chapter: Introduction to Update in Amyotrophic Lateral Sclerosis and Review of this Condition in Sportsmen

A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice

Dendritic Spine Loss and Chronic White Matter Inflammation in a Mouse Model of Highly Repetitive Head Trauma

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