The effects of post-traumatic temperature manipulation or secondary hypoxia on histopathological and behavioral outcome after fluid percussion brain injury

Date of Award




Degree Name

Doctor of Philosophy (Ph.D.)



First Committee Member

Edward J. Green - Committee Chair

Second Committee Member

W. Dalton Dietrich - Committee Member


Axonal injury is an important consequence of human head trauma and leads to an increase in mortality. Few experimental studies have been done to accurately document patterns of axonal injury at both moderate and severe injury levels. Furthermore, the effects on axonal damage of certain clinically relevant post-insult manipulations whether beneficial (hypothermia) or detrimental (hyperthermia or hypoxia) have not been extensively assessed. In addition, although long-term disability after human head trauma does exist, the influences of secondary hypoxia after traumatic brain injury on behavioral outcome measures has not been well characterized.These experiments evaluated the effects of post-insult manipulations on axonal damage after fluid percussion traumatic brain injury (TBI), and characterized both histopathologically and behaviorally the effects of secondary hypoxia in a rat model.Animals subjected to moderate TBI showed a distinct regional and temporal profile of axonal damage which was exacerbated by severe injury. Post-insult hypothermia or hyperthermia did not consistently effect the degree of axonal damage, as assessed using b -amyloid precursor protein ( b -APP) or a silver stain. A secondary hypoxic insult exacerbated the TBI-associated behavioral deficits and gray matter necrosis without significantly altering axonal damage.These experiments document a distinct regional and temporal profile of axonal damage in the rat after FP brain injury, and demonstrate that b -APP immunostaining can reveal patterns of axonal damage that are similar to those observed using the more traditional silver stain method, but with enhanced sensitivity. The experiments also demonstrate that in the current TBI model, secondary hypoxic insult exacerbates both histopathological and behavioral consequences of TBI, illustrating the general utility of this model for mimicking human head trauma.


Biology, Neuroscience; Health Sciences, Medicine and Surgery

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