title: Age is a determinant of leukocyte infiltration and loss of cortical volume after traumatic brain injury.
abstract: There is increasing evidence that the inflammatory response differs in the injured developing brain as compared to the adult brain. Here we compared cerebral blood flow and profiled the inflammatory response in mice that had been subjected to traumatic brain injury (TBI) at postnatal day (P)21 or at adulthood. Relative blood flow, determined by laser Doppler, revealed a 30% decrease in flow immediately after injury followed by prominent hyperemia between 7 and 35 days after injury in both age groups. The animals were euthanized at 1-35 days after injury and the brains prepared for the immunolocalization and quantification of CD45-, GR-1-, CD4- and CD8-positive (+) cells. On average, the number of CD45+ leukocytes in the cortex was significantly higher in the P21 as compared to the adult group. A similar trend was seen for GR-1+ granulocytes, whereas no age-related differences were noted for CD4+ and CD8+ cells. While CD45+ and GR-1+ cells in the P21 group remained elevated, relative to shams, over the first 2 weeks after injury, the adult group showed a time course limited to the first 3 days after injury. The loss of ipsilateral cortical volumes at 2 weeks after injury was significantly greater in the adult relative to the P21 group. While the adult group showed no further change in cortical volumes, there was a significant loss of cortical volumes between 2 and 5 weeks after injury in the P21 group, reaching values similar to that of the adult group by 5 weeks after injury. Together, these findings demonstrate age-dependent temporal patterns of leukocyte infiltration and loss of cortical volume after TBI.
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, CA 94143-0112, USA.
authors.forename: Catherine P
authors.initials: CP
authors.lastname: Claus
authors.forename: Kyoko
authors.initials: K
authors.lastname: Tsuru-Aoyagi
authors.forename: Hita
authors.initials: H
authors.lastname: Adwanikar
authors.forename: Breset
authors.initials: B
authors.lastname: Walker
authors.forename: Hovhannes
authors.initials: H
authors.lastname: Manvelyan
authors.forename: William
authors.initials: W
authors.lastname: Whetstone
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Noble-Haeusslein
mesh_terms: D000367:Age Factors; D000818:Animals; D001930:Brain Injuries / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL