RT Journal Article
SR Electronic
T1 Greater neurodegeneration and behavioral deficits after single closed head traumatic brain injury in adolescent vs adult mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 577999
DO 10.1101/577999
A1 Fernanda Guilhaume-Correa
A1 Shelby M. Cansler
A1 Emily M. Shalosky
A1 Michael D. Goodman
A1 Nathan K. Evanson
YR 2019
UL http://biorxiv.org/content/early/2019/03/16/577999.abstract
AB Introduction Traumatic brain injury (TBI) is a major public health concern affecting 2.8 million people per year, of which about 1 million are children under 19 years old. Animal models of TBI have been developed and used in multiple ages of animals, but direct comparisons of adult and adolescent populations are rare. The current studies were undertaken to directly compare outcomes between adult and adolescent mice, using a closed head, single impact model of TBI.Methods Six-week-old adolescent and 9-week-old adult male mice were subjected to TBI using a closed head weight drop model. Histological measures for neurodegeneration, gliosis, and microglial neuroinflammation, and behavioral tests of locomotion and memory were performed.Results Adolescent TBI mice have increased mortality (X2= 20.72, p < 0.001) compared to adults. There is also evidence of hippocampal neurodegeneration in adolescents, but not adults. Presence of hippocampal neurodegeneration correlates with histologic activation of microglia, but not with increased markers of astrogliosis. Adults and adolescents have similar locomotion deficits after TBI that recover by 16 days post-injury. Adolescents have memory deficits as evidenced by impaired novel object recognition performance 3 and 16 days post injury (F1,26 = 5.23, p = 0.031) while adults do not.Conclusions Adults and adolescents within a close age range (6-9 weeks) respond to TBI differently. Adolescents are more severely affected by mortality, neurodegeneration, and inflammation in the hippocampus compared to adults. Adolescents, but not adults, have worse memory performance after TBI that lasts up to 16 days post injury.ANOVAAnalysis of VarianceDPIDays post-injuryFJ-BFluoro-jade BGFAPGlial fibrillary acidic proteinIba-1ionized calcium-binding adapter protein-1NORnovel object recognitionPBSphosphate buffered salinePNDpost-natal dayTBItraumatic brain injury