Increasing recovery
time between injuries improves cognitive outcome after repetitive mild
concussion brain injuries in mice

WP, Zhang J, Mannix R, Whalen MJ. Neurosurgery, 2012; ahead of print

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

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.

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?

by: Jane McDevitt MS, ATC, CSCS
by: Jeffrey Driban


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