期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 39, 期 11, 页码 2196-2209出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X18786633
关键词
Animal model; brain trauma; cerebral blood flow; endothelium; inflammation
资金
- NIA NIH HHS [RF1 AG051506] Funding Source: Medline
- NICHD NIH HHS [R21 HD086385] Funding Source: Medline
- NINDS NIH HHS [R01 NS092847, R01 NS091573] Funding Source: Medline
Repetitive mild traumatic brain injury during adolescence can induce neurological dysfunction through undefined mechanisms. Interleukin-1 (IL-1) contributes to experimental adult diffuse and contusion TBI models, and IL-1 antagonists have entered clinical trials for severe TBI in adults; however, no such data exist for adolescent TBI. We developed an adolescent mouse repetitive closed head injury (rCHI) model to test the role of IL-1 family members in post-injury neurological outcome. Compared to one CHI, three daily injuries (3HD) produced acute and chronic learning deficits and emergence of hyperactivity, without detectable gliosis, neurodegeneration, brain atrophy, and white matter loss at one year. Mature IL-1 beta and IL-18 were induced in brain endothelium in 3HD but not 1HD, three hit weekly, or sham animals. IL-1 beta processing was induced cell-autonomously in three-dimensional human endothelial cell cultures subjected to in vitro concussive trauma. Mice deficient in IL-1 receptor-1 or caspase-1 had improved post-injury Morris water maze performance. Repetitive mild CHI in adolescent mice may induce behavioral deficits in the absence of significant histopathology. The endothelium is a potential source of IL-1 beta and IL-18 in rCHI, and IL-1 family members may be therapeutic targets to reduce or prevent neurological dysfunction after repetitive mild TBI in adolescents.
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