Outcome after repetitive mild traumatic brain injury is temporally related to glucose uptake profile at time of second injury

Repeated mild traumatic brain injury (rmTBI) results in worsened outcomes, compared with a single injury, but the mechanism of this phenomenon is unclear. We have previously shown that mild TBI in a rat lateral fluid percussion model results in globally depressed glucose uptake, with a peak depression at 24 h that resolves by 16 days post-injury. The current study investigated the outcomes of a repeat injury conducted at various times during this period of depressed glucose uptake. Adult male rats were therefore subjected to rmTBI with a latency of 24 h, 5 days, or 15 days between injuries, followed by assessment of motor function, histopathology, and glucose uptake using positron emission tomography (PET). Rats that received a 24 h rmTBI showed significant deficits in motor function tasks, as well as significant increases in lesion volume and neuronal damage. The level of microglial and astrocytic activation also was associated with the timing of the second impact. Finally, rmTBI with latencies of 24 h and 5 days showed significant alterations in [¹⁸F]fluorodeoxyglucose uptake, compared with baseline scans. Therefore, we conclude that the state of the metabolic environment, as indicated by FDG-PET at the time of the repeat injury, significantly influences neurological outcomes.