Repeated mild traumatic brain injury: mechanisms of cerebral vulnerability

J Neurotrauma. 2013 Jan 1;30(1):30-8. doi: 10.1089/neu.2012.2399.


Among the 3.5 million annual new head injury cases is a subpopulation of children and young adults who experience repeated traumatic brain injury (TBI). The duration of vulnerability after a single TBI remains unknown, and biomarkers have yet to be determined. Decreases in glucose metabolism (cerebral metabolic rate of glucose [CMRglc]) are consistently observed after experimental and human TBI. In the current study, it is hypothesized that the duration of vulnerability is related to the duration of decreased CMRglc and that a single mild TBI (mTBI) increases the brain's vulnerability to a second insult for a period, during which a subsequent mTBI will worsen the outcome. Postnatal day 35 rats were given sham, single mTBI, or two mTBI at 24-h or 120-h intervals. (14)C-2-deoxy-D-glucose autoradiography was conducted at 1 or 3 days post-injury to calculate CMRglc. At 24 h after a single mTBI, CMRglc is decreased by 19% in both the parietal cortex and hippocampus, but approached sham levels by 3 days post-injury. When a second mTBI is introduced during the CMRglc depression of the first injury, the consequent CMRglc is depressed (36.5%) at 24 h and remains depressed (25%) at 3 days. In contrast, when the second mTBI is introduced after the metabolic recovery of the first injury, the consequent CMRglc depression is similar to that seen with a single injury. Results suggest that the duration of metabolic depression reflects the time-course of vulnerability to second injury in the juvenile brain and could serve as a valuable biomarker in establishing window of vulnerability guidelines.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Behavior, Animal / physiology
  • Brain Injuries / etiology
  • Brain Injuries / metabolism*
  • Brain Injuries / physiopathology
  • Cerebral Cortex / injuries
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / physiopathology
  • Depression / complications
  • Depression / metabolism
  • Depression / physiopathology
  • Disease Models, Animal
  • Glucose / metabolism
  • Male
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Recurrence
  • Time Factors


  • Glucose