Molecular correlates of age-specific responses to traumatic brain injury in mice.
Aged traumatic brain injury (TBI) patients suffer higher rates of mortality and disability than younger patients. Cognitive problems common to TBI patients are associated with damage to the hippocampus, a central locus of learning and memory. To investigate the molecular mechanisms of age-related vulnerability to brain injury in a mouse model of TBI, we studied the effects of TBI on hippocampal gene expression in young and aged mice. Young and aged male C57Bl/6 mice were subjected to sham injury or TBI and sacrificed 24 h post-injury. We used laser capture microdissection to obtain pure populations of neurons from the CA1, CA3, and dentate gyrus subfields of the hippocampus. We compared injury-induced gene expression in hippocampal neurons of young and aged mice using quantitative ribonuclease protection assay analysis of linearly amplified mRNA from laser captured neurons. Both increased age and TBI were associated with increased expression of neuroprotective (brain-derived neurotrophic factor), pro-inflammatory (interleukin-1beta), and proapoptotic (caspase-3) genes in mouse hippocampal neurons. Our data support previous reports that suggested the CA3 subregion is highly susceptible to fluid percussion TBI and that age-related changes in gene expression are one potential mechanism of increased vulnerability of the aged brain to TBI.
Shah
Syed A
SA
Department of Anesthesiology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0830, USA.
Prough
Donald S
DS
Garcia
Jeanna M
JM
DeWitt
Douglas S
DS
Hellmich
Helen L
HL
D000375:Aging / Q000235:genetics*; D000818:Animals; D001930:Brain Injuries / Q000235:genetics* / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis / Q000235:genetics; D053148:Caspase 3 / Q000032:analysis / Q000235:genetics; D018891:Dentate Gyrus; D004195:Disease Models, Animal; D015870:Gene Expression / Q000235:genetics; D006624:Hippocampus / Q000473:pathology; D053583:Interleukin-1beta / Q000032:analysis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis
D019208:Brain-Derived Neurotrophic Factor; D053583:Interleukin-1beta; D012333:RNA, Messenger; D053148:Caspase 3