Modeling Chronic Traumatic Encephalopathy: The Way Forward for Future Discovery

Abstract

Despite the extensive media coverage associated with the diagnosis of chronic traumatic encephalopathy (CTE), our fundamental understanding of the disease pathophysiology remains in its infancy. Only recently have scientific laboratories and personnel begun to explore CTE pathophysiology through the use of preclinical models of neurotrauma. Some studies have shown the ability to recapitulate some aspects of CTE in rodent models, through the use of various neuropathological, biochemical, and/or behavioral assays. Many questions related to CTE development, however, remain unanswered. These include the role of impact severity, the time interval between impacts, the age at which impacts occur, and the total number of impacts sustained. Other important variables such as the location of impacts, character of impacts, and effect of environment/lifestyle and genetics also warrant further study. In this work, we attempt to address some of these questions by exploring work previously completed using single- and repetitive-injury paradigms. Despite some models producing some deficits similar to CTE symptoms, it is clear that further studies are required to understand the development of neuropathological and neurobehavioral features consistent with CTE-like features in rodents. Specifically, acute and chronic studies are needed that characterize the development of tau-based pathology.

Effects of concussion on the blood–brain barrier in humans and rodents

“…130 A series of contributions from Petraglia et al [131][132][133][134] have described the pathological and behavioral effects of repetitive TBI in a closed skull model of TBI in mice and demonstrated the clearly greater effects of multiple impacts on a variety of behavioral measures. While much attention has been focused on the cellular (both neural and glial) response to TBI, as well as its behavioral consequences, less attention has been directed toward understanding possible effects of TBI on cerebral vasculature.…”

Is There a Link to Traumatic Brain Injury?

“…With hyper-phosphorylation, the tau proteins misfold and form aggregates, which then contribute to the formation of neurofibrillary tangles. [29][30][31][32] …”

Elucidating Mechanisms of Neurobehavioral Dysfunction in a Rodent Model of Traumatic Brain Injury

“…One-way ANOVA revealed a significant difference in EB absorbance in the left PFC following blast exposure (F (3,12) = 31.350, p < 0.001). Dunnett's post-hoc analyses revealed bTBI significantly increased EB absorbance in the left PFC at 0.5 h (q = 8.844, p < 0.001) and 6 h (q = 3.491, p < 0.05) (Figure 4.2A).…”

“…cleavage at 24 h post-bTBI (F(3,16) = 5.533, p < 0.01). Caspase-3 cleavage significantly increased in the left PFC of bTBI rats (t = 3.251, p < 0.05), but was not significantly increased in the left PFC of SAL+bTBI rats (t = 1.200, p > 0.05) (Bonferroni's post-hoc analysis)(Figure 4.8A).…”

“…experimental groups: (1) control, (2) SAL,(3) bTBI 24 h, and (4) SAL+bTBI 24 h (n = 5).Animals were euthanized and had tissue prepared as previously described. Protein samples were prepared by sonication in hot (85-95 o C) 1% sodium docecyl sulfate (SDS; Sigma) as previously described(O'Callaghan and Sriram, 2004).…”