Age-dependent release of high-mobility group box protein-1 and cellular neuroinflammation after traumatic brain injury in mice |
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Authors: | Kyria M. Webster Mujun Sun Peter J. Crack Terence J. O'Brien Sandy R. Shultz Bridgette D. Semple |
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Affiliation: | 1. Department of Medicine (Royal Melbourne Hospital), The University of Melbourne, Parkville, Victoria, Australia;2. Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, Victoria, Australia;3. Department of Medicine (Royal Melbourne Hospital), The University of Melbourne, Parkville, Victoria, Australia Department of Neuroscience, Monash University, Melbourne, Victoria, Australia |
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Abstract: | Accumulating research suggests that children may be more vulnerable to poor long-term outcomes after traumatic brain injury (TBI) compared to adults. The neuroinflammatory response, known to contribute to neuropathology after TBI, appears to differ depending upon age-at-insult, although this response has not been well-characterized. Elevated levels of a key initiator of inflammation, high-mobility group box protein 1 (HMGB1), have been associated with worsened outcomes after TBI in young patients. This study therefore aimed to characterize the acute time course of key mediators of the inflammatory cascade, including HMGB1, after pediatric and adult TBI. Male C57Bl/6 mice were subjected to severe controlled cortical impact or a sham control surgery, at either early adulthood (8–10 weeks) or a pediatric age (3 weeks). Cortical tissue was collected for Western blot detection of astrocyte and microglial activation (GFAP and CD68) and HMGB1 at 2 hr, 6 hr, 24 hr, 3 days, and 7 days postinjury, and serum was collected for enzyme-linked immunoassays to quantify peripheral HMGB1. An additional cohort of brains was harvested at 3 day postinjury for immunofluorescence staining. Results demonstrated a temporal profile of CD68, GFAP, and HMGB1 after TBI relative to sham, which differed between the adult and pediatric cohorts. An increase in peripheral HMGB1 was found in serum from pediatric TBI mice, which was not evident in adult serum. Together, these findings demonstrate that HMGB1 and the downstream cellular inflammatory response are influenced by age-at-insult, which may be an important consideration for treatment strategies aiming to ameliorate this response after TBI. |
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Keywords: | age high mobility group box protein 1 inflammation pediatric RRID:AB_10013382 RRID:AB_10679369 RRID:AB_11212597 RRID:AB_1141557 RRID:AB_141607 RRID:AB_141637 RRID:AB_2224402 RRID:AB_2298772 RRID:AB_2305186 RRID:AB_2534105 RRID:AB_2617143 RRID:AB_444360 RRID:AB_783595 traumatic brain injury |
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