Date of Presentation
5-5-2022 12:00 AM
College
School of Osteopathic Medicine
Poster Abstract
Traumatic brain injury (TBI) affects approximately 3.8 million Americans a year and results in complex neuropathological and neurocognitive sequelae. Animal models of TBI attempt to replicate the impact forces and pathology of injury in humans. However, in these models, the forces generated at the time of impact are poorly understood. Nonetheless, a variety of shear and strain forces generated at the time of impact can produce diffuse axonal injury. Injury to axons and neurons across a variety of brain regions resulting from axonal injury underlies the cognitive and behavioral impairments observed after TBI. Three critical brain regions, the corpus callosum (CC), cerebellum (Cb), and the locus coeruleus (LC), are critical for interhemispheric communication, motor coordination, and regulation of higher cognitive function. However, axonal injury in these brain regions is poorly studied across animal injury models. To address these gaps in our knowledge, we determined head acceleration forces generated in two common experimental TBI models and quantified patterns of neuronal injury markers in the CC, Cb, and LC produced by these models. Specifically, a closed head-electronic controlled cortical impact (CH-eCCI) model and a frontal- impact Maryland weight drop (MWD) model were used to compare different impact trajectories. Force data were correlated with neurosilver stain markers to identify injured fibers and cell bodies of injured neurons. We found that g-force increased with both higher CH-eCCI impact velocities and vertical impact depth. Similarly, acceleration forces increased with higher drop heights and horizontal impact throw in the MWD model. G-force measurements exceeded device limits (400Gs) before standard laboratory parameters for mild or moderate CH-eCCI could be evaluated (i.e., 2.5 mm or 3.5 mm @ 5.5m/s). Neurosilver labeling of axonal injury in the CC, Cb, and LC after CH-eCCI injury was found to be dependent on the severity of injury. Although there was a clear relationship between injury severity and silver staining in the CC and Cb, more data is needed to determine whether the same relationship exists for labeling in the LC. These studies suggest that in these animal models, acceleration g-forces are 4-8 fold higher than those found in sports-related injuries (i.e.90-100Gs). Furthermore, axonal injury in the Cb and LC may be a critical contributor to the motor and cognitive deficits reported following injury.
Keywords
Traumatic Brain Injury, Diffuse Axonal Brain Injury, Animal Models, Brain, Biomechanical Phenomena
Disciplines
Animal Experimentation and Research | Biomechanics | Disease Modeling | Laboratory and Basic Science Research | Medicine and Health Sciences | Nervous System | Nervous System Diseases | Neurology | Pathological Conditions, Signs and Symptoms
Document Type
Poster
Included in
Animal Experimentation and Research Commons, Biomechanics Commons, Disease Modeling Commons, Laboratory and Basic Science Research Commons, Nervous System Commons, Nervous System Diseases Commons, Neurology Commons, Pathological Conditions, Signs and Symptoms Commons
Impact Forces and Patterns of Axonal Injury Differ Between Two Models of TBI
Traumatic brain injury (TBI) affects approximately 3.8 million Americans a year and results in complex neuropathological and neurocognitive sequelae. Animal models of TBI attempt to replicate the impact forces and pathology of injury in humans. However, in these models, the forces generated at the time of impact are poorly understood. Nonetheless, a variety of shear and strain forces generated at the time of impact can produce diffuse axonal injury. Injury to axons and neurons across a variety of brain regions resulting from axonal injury underlies the cognitive and behavioral impairments observed after TBI. Three critical brain regions, the corpus callosum (CC), cerebellum (Cb), and the locus coeruleus (LC), are critical for interhemispheric communication, motor coordination, and regulation of higher cognitive function. However, axonal injury in these brain regions is poorly studied across animal injury models. To address these gaps in our knowledge, we determined head acceleration forces generated in two common experimental TBI models and quantified patterns of neuronal injury markers in the CC, Cb, and LC produced by these models. Specifically, a closed head-electronic controlled cortical impact (CH-eCCI) model and a frontal- impact Maryland weight drop (MWD) model were used to compare different impact trajectories. Force data were correlated with neurosilver stain markers to identify injured fibers and cell bodies of injured neurons. We found that g-force increased with both higher CH-eCCI impact velocities and vertical impact depth. Similarly, acceleration forces increased with higher drop heights and horizontal impact throw in the MWD model. G-force measurements exceeded device limits (400Gs) before standard laboratory parameters for mild or moderate CH-eCCI could be evaluated (i.e., 2.5 mm or 3.5 mm @ 5.5m/s). Neurosilver labeling of axonal injury in the CC, Cb, and LC after CH-eCCI injury was found to be dependent on the severity of injury. Although there was a clear relationship between injury severity and silver staining in the CC and Cb, more data is needed to determine whether the same relationship exists for labeling in the LC. These studies suggest that in these animal models, acceleration g-forces are 4-8 fold higher than those found in sports-related injuries (i.e.90-100Gs). Furthermore, axonal injury in the Cb and LC may be a critical contributor to the motor and cognitive deficits reported following injury.