Acute and Persistent Alterations of Cerebellar Inflammatory Networks and Glial Activation in a Rat Model of Pediatric Mild Traumatic Brain Injury

Erik A Fraunberger, Pauline DeJesus, Elisa R Zanier, Timothy E Shutt, Michael J Esser

Research output: Contribution to journalArticlepeer-review

Abstract

Following a traumatic brain injury (TBI), inflammation is a well-documented but poorly understood phenomenon, especially at later time-points (i.e., beyond 72 h) and in brain areas outside the cortex. The cerebellum, important for motor and cognitive functioning, represents an area of the brain equally affected by TBI that is seldom evaluated despite its potential involvement in persistent deficits after injury. In the context of TBI and inflammation, most studies focus on severe TBI in adult males, with fewer studies on pediatric mild TBI in both sexes. Our study addresses this gap by profiling neurological function and cerebellar inflammation over time in the juvenile male and female rat brain following a mild, closed-head weight-drop injury (mTBI). At 24 h, 72 h, 7 days, and 21 days post-mTBI, animals were subjected to behavioral testing to evaluate TBI effects over time. Alongside behavioral deficits up to 7 days post-injury, inflammatory profiling by multi-plex enzyme-linked immunosorbent assay (ELISA) revealed increased inflammatory markers, including CXCL1, interleukin (IL)-5, and vascular endothelial growth factor alpha (VEGFα), in plasma at 24-72 h and in the cerebellum at 72 h post-injury. Network analysis of cytokines also showed increased inter-relationships between multiple mediators at all time-points, emphasizing the persistent and dynamic changes to inflammatory patterns after mTBI. Transcript levels of microglia/macrophage activation markers, including Iba1 and CX3CR1, were significantly elevated at 7 days post-TBI in both sexes, and at 21 days in females, suggesting activation of immune cells in the cerebellum. When examining the protein expression of GFAP and CX3CR1, a significant increase in CX3CR1 was noted in males at 21 days but not in females. Characterizing the evolution of cerebellar inflammation in pediatric mTBI provides insight into potential mechanisms of persistent changes that could contribute to neurological dysfunction.

Original languageEnglish
Pages (from-to)1315-1330
Number of pages16
JournalJournal of Neurotrauma
Volume37
Issue number11
DOIs
Publication statusPublished - Jun 1 2020

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