Increasing recovery time between injuries improves cognitive outcome after repetitive mild concussion brain injuries in mice
Meehan WP, Zhang J, Mannix R, Whalen MJ. Neurosurgery, 2012; ahead of print
Researchers have suggested that there are long-term cumulative effects that result from repetitive concussions (e.g., cognitive deficits). However, it is unknown if the time interval between repeat concussions may influence the risk of long-term issues. Therefore, the researchers wanted to determine the effect of time interval between repeat concussions on the cognitive function of mice. Researchers used a weight-drop model to subject 70 anesthetized mice to 1, 3, 5, or 10 mild concussions, each 1 day apart, to evaluate cumulative effects of concussions. Additionally, 56 mice were subjected to 5 concussions daily, weekly, or monthly to assess the effect of time interval between concussions. The authors used a weight drop model that produced a mild concussion characterized by a short loss of consciousness, occasional brief seizures, and no mortality. Functional performance and long-term cognitive deficits were measured by the ability of the mice to navigate through the Morris water maze (MWM) 24 hours, 1 month, and 1 year after the final concussion compared to mice with no concussion injury. The authors found that there was no difference in MWM performance directly following the concussion injury between control mice and mice with 1 concussion. However, they found mice that sustained 5 consecutive days of concussions performed remarkably worse on the MWM compared to control mice starting after the 3rd consecutive concussion. Furthermore, mice that had 5 concussion injuries 1-week apart also performed worse on the MWM compared to control mice. Those mice that had 5 daily concussions and 5 weekly concussions were still performing worse on the MWM 1 month after their final concussion injury compared to the control mice. There were no deficits in MWM trials between control mice and those that had 5 concussions each 1-month apart. In fact, those mice that had 5 concussions 1-month apart were similar to control mice on the MWM 1 month and 1 year after their last concussion injury. At one-year follow-up those mice that sustained 5 daily concussions performed worse on MWM compared to control. However, there were no differences in the MWM performance at one year follow-up between mice that had weekly concussions and control mice.
Previous concussion research has suggested that multiple concussions can become cumulative, however, there is little research done on the time between multiple mild concussions and its cumulative effect one year post injuries. Mice that sustained injuries daily or weekly performed worse than control mice on the MWM. In contrast, mice receiving 1 concussion per month for 5 months were no different than the control mice. Researchers suggest that not only can these injuries become cumulative, but there is also a time period (i.e., daily or weekly concussions) that may increase the risk of cognitive impairment. When the time between repetitive concussions is short it increases the risk of permanent long-term consequences. This study shows a possible window of vulnerability of at least 7 days using this head model. Though the authors believed they were giving mice a mild concussion there is no severity data to evaluate if this would correlate to a mild concussion injury. Further research may be needed to test how severity of concussion injury and the length of time between concussions interact to influence the risk of long-term cognitive impairment. The authors also demonstrated that allowing at least one month between injuries seems to decreases the cumulative effect on cognition at the concussion severity they tested. Do you think future concussion return-to-play guidelines will be based on a “window of vulnerability,” or be based around a conservative amount of days after injury?
Written by: Jane McDevitt MS, ATC, CSCS
Reviewed by: Jeffrey Driban
Related Posts:Meehan WP 3rd, Zhang J, Mannix R, & Whalen MJ (2012). Increasing Recovery Time Between Injuries Improves Cognitive Outcome After Repetitive Mild Concussive Brain Injuries in Mice. Neurosurgery PMID: 22743360