Preclinical characterization of traumatic brain injury pathophysiology and associated functional outcomes
Kinder, Holly Ann
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Traumatic brain injury (TBI) is a leading cause of long-term disability and death in the United States. Young children are particularly susceptible to sustaining a concussive TBI as the result of a fall, and it is well established that TBI at a young age can lead to short- and long-term functional deficits in learning and memory, behavior, and motor function. The development of functional deficits may be attributed to damage to cortical regions, sub-cortical white matter, or major limbic structures such as the hippocampus, either as a result of primary or secondary injury mechanisms. The secondary injury cascade, usually characterized by pathophysiologic changes like blood brain barrier damage, decreased cerebral blood flow, astrogliosis, and microglia activation, leads to neuronal death, axonal injury, white matter disruption and ultimately, the development of functional impairments. Currently, there are no Food and Drug Administration (FDA)-approved therapies for TBI that demonstrate significant neuroprotective or restorative effects that mitigate the development of functional deficits. Therefore, it is of interest to study TBI pathophysiology and corresponding functional responses in large animal models like the pig that may have more similar responses to injury and greater predictive power in identifying potential therapeutics. The objectives of these studies were to 1) develop a piglet TBI model and characterize pathophysiologic mechanisms in response to injury severity and time course, and 2) assess changes in cognition, behavior, and motor function as a result of TBI.