College of Science and Health Theses and Dissertations

Date of Award

Winter 3-22-2019

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Biological Science

First Advisor

Dr. Dorothy Kozlowski

Second Advisor

Dr. Margaret Bell

Third Advisor

Dr. Eric Norstrom

Abstract

Although concussions, especially those in athletes and military, have become a popular focus of neurotrauma research, subconcussions occur with higher frequency and are less well-studied. A subconcussion is loosely defined as an impact to the head that does not result in a diagnosable concussion but can result in neuronal alterations. Repeat subconcussions have been shown to produce behavioral impairments along with neuropathology that is similar to or worse than those seen in a single concussion injury. These studies have primarily included male subjects. Given the potential effects of hormones and NIH’s call for sex-inclusion in biomedical research, assessing female responses to injury is essential. The current study was designed to model repeat subconcussions in the adult rat and examine sex differences in behavioral responses to injury. Using a model of closed head injury previously created in our lab, this study modified the intensity of the impact to create a subconcussive impact. All rats received a single concussion, single subconcussion, repeat subconcussion (five impacts, 24-hours apart), or sham (no impact) injury. The repeat subconcussive injury was patterned following preliminary data from our lab. Female rats received the first impact on the day of proestrus, when estrogen concentrations peak during the estrous cycle. Behavioral tests were administered two hours post impact through 31 days post-injury. All animals with a single concussion or repeat subconcussion showed deficits in locomotion, righting reflexes, and recognition memory, while animals with a single subconcussion did not. Repeat subconcussions produced deficits similar to a single concussion in righting reflex and recognition memory, but locomotor deficits were greater in rats with repeat subconcussions. When assessing sex differences in the behavioral responses to the repeat subconcussive model, female rats showed greater deficits than males in righting reflexes, locomotion, and vestibular function. Males showed greater increases in anxiety-like behaviors than the females. This study established a model of subconcussive impact where a single

subconcussive impact resulted in little to no behavioral deficits but repeat subconcussive impacts resulted in deficits that are similar to or worse than a single concussion. Our data also suggest that females may experience more deleterious effects in certain outcomes following both concussive and subconcussive impacts, which supports some clinical findings. Further experiments will need to be done to examine sex differences in the neuropathology.

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