A CLINICALLY RELEVANT CLOSED-HEAD MODEL OF SINGLE AND REPEAT CONCUSSIVE INJURIES IN THE ADULT RAT USING A CONTROLLED CORTICAL IMPACT DEVICE
Date of Award
Master of Science (MS)
Dorothy Kozlowski, PhD
Eric Norstrom, PhD
Janice Urban, PhD
Recently, cases of multiple concussions, or mild traumatic brain injury, in athletes have received increased attention. Compared to single concussion (sTBI), repeat concussions (rTBI) can produce significant long-term consequences and increased risk for neurodegenerative disease. However, mechanisms underlying this difference are poorly understood and are best elucidated using an animal model. Closed-head models of rTBI have been developed in mice and juvenile rats, but few have been developed in the adult rat. To the best of our knowledge, there is no closed-head model using a commercially available device, including the Controlled Cortical Impact (CCI) device.
We developed a clinically relevant closed-head injury model of concussion in the adult rat using a Leica CCI device. Rats were placed in a stereotax frame without ear-bars, on a foam-bed base. The head was stabilized against a Plexiglas frame to control impact while allowing head movement. A 6.5 m/s impact was delivered onto the head surface over the sensorimotor-cortex at a depth of 10.0 mm from the skin. rTBI animals received 3 injuries, 48 hours apart. A subset of sTBI animals received two subsequent exposures to anesthesia (sTBIac), 48 hours apart, to mimic the extra exposure experienced by the rTBI animals.
We initially created a model of sTBI before continuing to examine rTBI. Sham and sTBI rats were initially assessed at days 1-3 post injury using tests of memory (Novel Object Recognition), forelimb coordination (foot fault) and activity/anxiety (open field). Blood corticosterone levels were measured pre-injury and pre-sacrifice (day 4). At this time point, sTBI animals showed memory deficits without locomotor deficits or an anxiety response.
The study was then expanded by adding rTBI animals and sTBI/sTBIac animals sacrificed 8 days after the initial injury. Rats were assessed at days 5-7 after the initial injury. Results indicate that both sTBI and rTBI animals show deficits in coordination and hypo-locomotion at day 5. Although sTBI rats showed no anxiety response rTBI rats did show anxiety (spent less time in the center of an open field). sTBI rats displayed memory deficits 3 days post-injury, but not day 7. rTBI rats continued to show memory deficits at day 7. Both had higher resting corticosterone levels post-injury compared to both their baseline levels and to sham and day 4 sTBI animals. No obvious gross pathology was observed on the cortical surface or in coronal sections. Our data presents a model of closed-head CCI in an adult rat that results in clinically relevant markers of concussion and an early delineation between single and repeat concussions.
Jamnia, Naseem, "A CLINICALLY RELEVANT CLOSED-HEAD MODEL OF SINGLE AND REPEAT CONCUSSIVE INJURIES IN THE ADULT RAT USING A CONTROLLED CORTICAL IMPACT DEVICE" (2015). College of Science and Health Theses and Dissertations. 114.