Chronic Histopathological and Behavioral Outcomes of Experimental Traumatic Brain Injury in Adult Male Animals

Osier, Nicole Danielle; Carlson, Shaun W.; DeSanaAnthony,; Edward, DixonC.

doi:10.1089/neu.2014.3680

Cited by 90 publications

(79 citation statements)

References 308 publications

(428 reference statements)

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“…10,11,[13][14][15][16][17]111,[115][116][117][119][120][121] These deficits, as reviewed in Osier and colleagues 122 and Thompson and coworkers, 123 can exceed those seen in our model, match them, or be more transient, depending on the severity of the impact. 10,11,124 For example, one of the least severe of these approaches, mild midline fluid percussion 1.4 atmosphere impact to the dura, produces TBI with little or no contusive injury to the brain, but causes optic nerve damage, similar to that in our TBI model.…”

Section: Discussionsupporting

confidence: 49%

“…Our model recapitulates the sensory, motor, and emotional deficits seen after mild TBI in humans 134,[154][155][156] and in other animal models, 8,122 in conjunction with the initial injury being largely limited to axon tracts. 6,8 The device we use is relatively inexpensive to fabricate and thus potentially available to many researchers.…”

Section: Resultsmentioning

confidence: 75%

“…20 The behavioral deficits and brain pathology seen in various blast studies have been summarized in several recent reviews. 34,75,76,122 Blast tube models, however, often produce a complex injury, because exposing the entire animal can cause lung damage, leading to hypoxic brain injury, and compression of the heart and aorta, which in turn produces blood pressure surges that damage blood vessels. These additional variables complicate interpretation of the relationship of the primary blast itself to the brain injury.…”

Section: Comparison With Blast Models In Rodentsmentioning

confidence: 99%

“…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%

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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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Section: Discussionsupporting

confidence: 49%

Section: Resultsmentioning

confidence: 75%

Section: Comparison With Blast Models In Rodentsmentioning

confidence: 99%

Section: Comparison With Blast Models In Rodentsmentioning

confidence: 99%

See 2 more Smart Citations

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

View full text Add to dashboard Cite

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“…11 TBI causes neuronal injury through processes that begin on impact and continue for days to months or years post-injury. [12][13][14] There have been many hypotheses about the causes of this ongoing injury, 14,15 including involvement of tau pathology. [16][17][18][19][20] Recently, we proposed a possible mechanism, based on accumulation and spreading of a toxic form of tau protein, known as tau oligomers.…”

mentioning

confidence: 99%

Tau Oligomers Derived from Traumatic Brain Injury Cause Cognitive Impairment and Accelerate Onset of Pathology in Htau Mice

Gerson

Castillo-Carranza

Sengupta

et al. 2016

Journal of Neurotrauma

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Tau aggregation is a pathological feature of numerous neurodegenerative disorders and has also been shown to occur under certain conditions of traumatic brain injury (TBI). Currently, no effective treatments exist for the long-term effects of TBI. In some cases, TBI not only induces cognitive changes immediately post-injury, but also leads to increased incidence of neurodegeneration later in life. Growing evidence from our lab and others suggests that the oligomeric forms of tau initiate the onset and spread of neurodegenerative tauopathies. Previously, we have shown increased levels of brainderived tau oligomers in autopsy samples from patients diagnosed with Alzheimer's disease. We have also shown similar increases in tau oligomers in animal models of neurodegenerative diseases and TBI. In the current study, we evaluated the presence of tau oligomers in blast-induced TBI. To test the direct impact of TBI-derived tau oligomer toxicity, we isolated tau oligomers from brains of rats that underwent either a blast-or a fluid percussion injury-induced TBI. Oligomers were characterized biochemically and morphologically and were then injected into hippocampi of mice overexpressing human tau (Htau). Mice were cognitively evaluated and brains were collected for immunological analysis after testing. We found that tau oligomers form as a result of brain injury in two different models of TBI. Additionally, these oligomers accelerated onset of cognitive deficits when injected into brains of Htau mice. Tau oligomer levels increased in the hippocampal injection sites and cerebellum, suggesting that tau oligomers may be responsible for seeding the spread of pathology post-TBI. Our results suggest that tau oligomers play an important role in the toxicity underlying TBI and may be a viable therapeutic target.

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Intravenous Immunomodulatory Nanoparticle Treatment for Traumatic Brain Injury

Sharma

Ifergan²,

Kurz

et al. 2020

Annals of Neurology

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Objective There are currently no definitive disease‐modifying therapies for traumatic brain injury (TBI). In this study, we present a strong therapeutic candidate for TBI, immunomodulatory nanoparticles (IMPs), which ablate a specific subset of hematogenous monocytes (hMos). We hypothesized that prevention of infiltration of these cells into brain acutely after TBI would attenuate secondary damage and preserve anatomic and neurologic function. Methods IMPs, composed of US Food and Drug Administration–approved 500nm carboxylated‐poly(lactic‐co‐glycolic) acid, were infused intravenously into wild‐type C57BL/6 mice following 2 different models of experimental TBI, controlled cortical impact (CCI), and closed head injury (CHI). Results IMP administration resulted in remarkable preservation of both tissue and neurological function in both CCI and CHI TBI models in mice. After acute treatment, there was a reduction in the number of immune cells infiltrating into the brain, mitigation of the inflammatory status of the infiltrating cells, improved electrophysiologic visual function, improved long‐term motor behavior, reduced edema formation as assessed by magnetic resonance imaging, and reduced lesion volumes on anatomic examination. Interpretation Our findings suggest that IMPs are a clinically translatable acute intervention for TBI with a well‐defined mechanism of action and beneficial anatomic and physiologic preservation and recovery. Ann Neurol 2020;87:442–455

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Chronic Histopathological and Behavioral Outcomes of Experimental Traumatic Brain Injury in Adult Male Animals

Cited by 90 publications

References 308 publications

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

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

Tau Oligomers Derived from Traumatic Brain Injury Cause Cognitive Impairment and Accelerate Onset of Pathology in Htau Mice

Intravenous Immunomodulatory Nanoparticle Treatment for Traumatic Brain Injury

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