title: Repeated mild traumatic brain injury: mechanisms of cerebral vulnerability.
abstract: 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.
authors.affiliation: Department of Neurosurgery, University of California, School of Medicine, Los Angeles, CA 90095, USA. mprins@mednet.ucla.edu
authors.forename: Mayumi L
authors.initials: ML
authors.lastname: Prins
authors.forename: Daya
authors.initials: D
authors.lastname: Alexander
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Giza
authors.forename: David A
authors.initials: DA
authors.lastname: Hovda
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001930:Brain Injuries / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000293:injuries / Q000378:metabolism* / Q000503:physiopathology; D003863:Depression / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D013997:Time Factors
chemical_list: D005947:Glucose