Elucidating the role of compression waves and impact duration for generating mild traumatic brain injury in rats

Abstract

Background: In total, 3.8 million concussions occur each year in the US leading to acute functional deficits, but the underlying histopathologic changes that occur are relatively unknown. In order to improve understanding of acute injury mechanisms, appropriately designed pre-clinical models must be utilized.

Methods: The clinical relevance of compression wave injury models revolves around the ability to produce consistent histopathologic deficits. Mild traumatic brain injuries activate similar neuroinflammatory cascades, cell death markers and increases in amyloid precursor protein in both humans and rodents. Humans, however, infrequently succumb to mild traumatic brain injuries and, therefore, the intensity and magnitude of impacts must be inferred. Understanding compression wave properties and mechanical loading could help link the histopathologic deficits seen in rodents to what might be happening in human brains following concussions.

Results: While the concept of linking duration and intensity of impact to subsequent histopathologic deficits makes sense, numerical modelling of compression waves has not been performed in this context. In this interdisciplinary work, numerical simulations were performed to study the creation of compression waves in an experimental model.

Conclusion: This work was conducted in conjunction with a repetitive compression wave injury paradigm in rats in order to better understand how the wave generation correlates with histopathologic deficits.

Keywords: Finite volume modelling; apoptosis; compression wave; pre-clinical model; traumatic brain injury.

Figure 1

Geometry of Sensor Layout. A two dimensional representation shows the geometrical configuration of the problem.

Figure 2

Contour Plot 2D Pressure. Domain pressure profile shown at different times provides initial conditions and follows the shock and expansion wave development and propagation.

Figure 3

L2 Error. A log-log plot shows converging simulation results with increasing grid resolution.

Figure 4

x-t Diagram. An x-t pressure contour plot shows the evolution of the shock and expansion waves after the diaphragm bursts.

Figure 5

Pressure vs. Time by Sensor. A line plot provides a comparison between experiment and simulation. The experiment uses pressure taps to measure gage pressure while the simulation uses a point probe to measure static pressure.

Figure 6

Acute Pathophysiology. H&E staining reveals nuclear enlargement and fragmentation in the contralateral prefrontal cortex 72 hours post repetitive TBI. A significant increase in APP was also observed χ² = 81, p<0.001. Scale bar = 20μm.

Figure 7

Neuronal Degeneration. A significant increase in fluorojade B was seen in the contralateral prefrontal cortex and hippocampus 72 hours following repetitive TBI. Thioflavin shows tau hyperphosphorylation and protein aggregation 72 hours following repetitive TBI. **=p<0.01, ***p<0.001. Scale bar = 50μm.