title: Differential expression of cytokines and chemokines during secondary neuron death following brain injury in old and young mice.
abstract: Adverse effects of age on the outcome of brain injury are well documented, but the mechanism is not well understood. Enhanced expression of proinflammatory cytokines and chemokines has long been linked to neuronal and glial responses to brain injury. In the present study, we used retrograde degeneration of thalamus as a model for secondary neuron death after cortical injury. We investigated the inflammatory component of glial responses to injury by determining mRNA expression of cytokines (TNF-alpha, IL-6, IL-1beta and IFN-gamma), chemokines (MCP-1 and RANTES) and iNOS in thalamus at day 0, 1, 3 and 7 after visual cortex ablation in mice aged 24 (old) and 4 months (young). Old mice demonstrated higher basal expression of TNF-alpha, IL-6, IL-1beta, MCP-1, RANTES and iNOS than young mice, while basal IFN-gamma expression was lower in the brains of older mice. Following injury, thalami of old mice demonstrated higher gene expression of TNF-alpha, IL-1beta, MCP-1, RANTES, and iNOS than young mice. Maximal expression of these five genes was observed 1 day following injury. IL-6 showed maximal gene expression 3 days after injury. By contrast, the increases in IFN-gamma expression after injury were smaller in old than in young mice. Our data demonstrate that both the baseline levels and the responses to injury of specific inflammatory molecules increase during aging. The increased expression of these critical molecules in inflammatory cascades may be responsible for increased secondary neuron death after injury in aging brain, suggesting that strategies to reduce these age-specific differences may help in the development of specific targets for pharmacologic intervention for the aging population.
authors.affiliation: Department of Anatomy and Cell Biology, University of Kansas Medical Center, 3901 Rainbow, Kansas City, KS 66160-7400, USA.
authors.forename: Rajat
authors.initials: R
authors.lastname: Sandhir
authors.forename: Veena
authors.initials: V
authors.lastname: Puri
authors.forename: Robert M
authors.initials: RM
authors.lastname: Klein
authors.forename: Nancy E J
authors.initials: NE
authors.lastname: Berman
mesh_terms: D000367:Age Factors; D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013788:Thalamus / Q000166:cytology / Q000378:metabolism; D013997:Time Factors
chemical_list: D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger