Spatial Distribution of Neuropathology and Neuroinflammation Elucidate the Biomechanics of Fluid Percussion Injury

Abstract

Diffuse brain injury is better described as multi-focal, where pathology can be found adjacent to seemingly uninjured neural tissue. In experimental diffuse brain injury, pathology and pathophysiology have been reported far more lateral than predicted by the impact site. We hypothesized that local thickening of the rodent skull at the temporal ridges serves to focus the intracranial mechanical forces experienced during brain injury and generate predictable pathology. We demonstrated local thickening of the skull at the temporal ridges using contour analysis on magnetic resonance imaging. After diffuse brain injury induced by midline fluid percussion injury (mFPI), pathological foci along the anterior-posterior length of cortex under the temporal ridges were evident acutely (1, 2, and 7 days) and chronically (28 days) post-injury by deposition of argyophilic reaction product. Area CA3 of the hippocampus and lateral nuclei of the thalamus showed pathological change, suggesting that mechanical forces to or from the temporal ridges shear subcortical regions. A proposed model of mFPI biomechanics suggests that injury force vectors reflect off the skull base and radiate toward the temporal ridge, thereby injuring ventral thalamus, dorsolateral hippocampus, and sensorimotor cortex. Surgically thinning the temporal ridge before injury reduced injury-induced inflammation in the sensorimotor cortex. These data build evidence for temporal ridges of the rodent skull to contribute to the observed pathology, whether by focusing extracranial forces to enter the cranium or intracranial forces to escape the cranium. Pre-clinical investigations can take advantage of the predicted pathology to explore injury mechanisms and treatment efficacy.

Diffuse traumatic brain injury substantially alters plasma growth hormone in the juvenile rat

“…In contrast, the number of somatostatin neurons in the somatosensory cortex decreased over time with animal age. We have previously observed significant neuropathology, identified by hyperintense deposition of argyrophilic reaction product (amino-cupric silver histochemical technique), in the somatosensory cortex of rats subjected to midline fluid percussion injury ( Beitchman et al 2021 ). This brain region is adjacent to the injury site and is particularly vulnerable to neurodegeneration ( Beitchman et al 2021 ).…”

“…We have previously observed significant neuropathology, identified by hyperintense deposition of argyrophilic reaction product (amino-cupric silver histochemical technique), in the somatosensory cortex of rats subjected to midline fluid percussion injury ( Beitchman et al 2021 ). This brain region is adjacent to the injury site and is particularly vulnerable to neurodegeneration ( Beitchman et al 2021 ). The spatial distribution of neuron injury and death after fluid percussion injury is primarily noted in the cortex and hippocampus ( Hicks et al 1996 ).…”

Age-At-Injury Influences the Glial Response to Traumatic Brain Injury in the Cortex of Male Juvenile Rats

“…Each immunohistochemistry stain was performed on 4 randomly selected brain slices located between bregma and lambda from the left hemisphere of each animal (total area of 160 μm), and 3 regions of interest [peri-injury, primary somatosensory barrel field (S1BF), perirhinal] per slice were analyzed. Based on our findings of the biomechanical mechanism of mFPI ( 27 ), and our previously published work on TBI-induced neuropathology in juvenile rats ( 13 ), we chose three cortical regions of interest for the current study. We selected two cortical areas that, based on our previous research, exhibit extensive pathology after mFPI (peri-injury and S1BF), as well as a remote cortical region for comparison.…”

Sleep, inflammation, and hemodynamics in rodent models of traumatic brain injury

“…The fluid impulse is delivered to the intact dura through an injury hub assembly attached to the skull ( Lifshitz et al, 2016 ). The forces applied to the brain are dissipated through the tissue and cause pathology at multiple sites, determined by the structural properties of the skull ( Beitchman et al, 2021 ).…”