Research Reports - Injury timing alters metabolic, inflammatory and functional outcomes following repeated mild traumatic brain injury

Neurobiol Dis. 2014 Oct;70:108-16

Weil ZM(1), Gaier KR(2), Karelina K(2)

Repeated head injuries are a major public health concern both for athletes, and
members of the police and armed forces. There is ample experimental and clinical
evidence that there is a period of enhanced vulnerability to subsequent injury
following head trauma. Injuries that occur close together in time produce greater
cognitive, histological, and behavioral impairments than do injuries separated by
a longer period. Traumatic brain injuries alter cerebral glucose metabolism and
the resolution of altered glucose metabolism may signal the end of the period of
greater vulnerability. Here, we injured mice either once or twice separated by
three or 20days. Repeated injuries that were separated by three days were
associated with greater axonal degeneration, enhanced inflammatory responses, and
poorer performance in a spatial learning and memory task. A single injury induced
a transient but marked increase in local cerebral glucose utilization in the
injured hippocampus and sensorimotor cortex, whereas a second injury, three days
after the first, failed to induce an increase in glucose utilization at the same
time point. In contrast, when the second injury occurred substantially later
(20days after the first injury), an increase in glucose utilization occurred that
paralleled the increase observed following a single injury. The increased glucose
utilization observed after a single injury appears to be an adaptive component of
recovery, while mice with 2 injuries separated by three days were not able to
mount this response, thus this second injury may have produced a significant
energetic crisis such that energetic demands outstripped the ability of the
damaged cells to utilize energy. These data strongly reinforce the idea that too
rapid return to activity after a traumatic brain injury can induce permanent
damage and disability, and that monitoring cerebral energy utilization may be a
tool to determine when it is safe to return to the activity that caused the
initial injury.

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