Behavioral consequences of minimal traumatic brain injury in mice.

Zohar O, Rubovitch V, Milman A, Schreiber S, Pick CG. Acta Neurobiol Exp (Wars). 2011;71(1):36-45.

Minor traumatic brain injuries (mTBI) are difficult to diagnose because they do not show clear signs of brain defects on an MRI or CT, however, patients typically present with cognitive, behavioral, and emotional problems. The purpose of this article was to determine a new model to demonstrate a way to simulate an mTBI in mice, and using behavioral and cognitive tests, assess mice response following the mTBI event. This article presents a modified weight drop model to induce brain injuries in mice without any structural consequences to the mouse brain (as determined by MRI). At least 10 mice were used for the experimental and control group. Mice were observed at 7, 30, 60, and 90 days post injury to determine the amount of recovery from the weight drop event by using a variety of tests (e.g., forced swimming test, Morris Water Maze, staircase test) to assess the mice behavior and long and short-term cognitive abilities. Following the closed head mTBI the results demonstrated that the overall health of the mice was not affected. The functional and neurological tests (e.g., neurological tests, strength tests, locomotive tests) were all normal as well as performance tasks to test pain threshold and anxiety state. However, following mTBI, testing demonstrated that long-lasting and potentially irreversible damage to learning ability and memory tasks were present. At 30 days post mTBI, mice had a difficult time improving their performance and needed significantly more time than the control mice to finish the task. In addition, the mice developed depressive-like behavior, measured by immobility for significantly longer periods of time, starting after day 3 of the injury. However, this model did induce apoptosis to neurons in the hippocampus and cortex, which is typically not seen in mTBIs.

Primary/external head trauma as seen during an mTBI event often leads to secondary/internal damage, which is still poorly understood. The development of this closed head mTBI model helps simulate an mTBI event without the production of external damage, brain tissue damage, surgical intrusion, or deep anesthesia. Previous models did not correlate as well to mTBI and it was difficult to determine if the effects of the blow were due to the primary or secondary damages. In addition, since there was apoptosis within the hippocampus, the portion of the brain that deals with memory, this may be why researchers found deficits within the experimental mice. Results depicted that mice had a difficult time accomplishing, learning, and improving on tasks that they had previously been trained to do. This is equivalent to a student athlete that sustained a mTBI typically having trouble performing in school. Also, following a mTBI event student athletes may feel tired, sluggish, and even depressed, which were also secondary effects that were seen in mice. Clinicians need to be aware that even if an mTBI event does not show up on imaging and functional and neurologic testing are normal, the athlete can still experience memory and learning deficits, and depression symptoms. Clinicians should consider that part of the treatment plan may need to include a decreased school work load in addition to being taken out of their respective sport. Currently it is unknown how long these deficits will remain present and the optimal treatment to improve them; if any. Currently our best line of defense is prevention, which first starts with athletes, parents, and coach education. In addition, this study may also suggest that children and adolescents should not be participating in contact sports due to a risk of permanent learning and memory deficits.

Written by: Jane McDevitt MS, ATC, CSCS
Reviewed by: Stephen Thomas