Search

Traumatic brain injury (TBI) can cause major disability and increases the risk of neurodegeneration. Post-TBI, there is infiltration of peripheral myeloid and lymphoid cells; there is limited information on the peripheral immune response post-TBI in the immature brain—where injury may interfere with neurodevelopment. We carried out two injury types in juvenile mice: invasive TBI with a controlled cortical impact (CCI) and repetitive mild TBI (rmTBI) using weight drop injury and analysed the response at 5- and 35-days post-injury. In the two models, we detected the brain infiltration of immune cells (e.g., neutrophils, monocytes, dendritic cells, CD4+ T cells, and NK cells). There were increases in macrophages, neutrophils, and dendritic cells in the spleen, increases in dendritic cells in blood, and increases in CD8+ T cells and B cells in lymph nodes. These results indicate a complex peripheral immune response post-TBI in the immature brain, with differences between an invasive injury and a repetitive mild injury. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a leading cause of disability and increases the risk of developing neurodegenerative diseases. The mechanisms linking TBI to neurodegeneration remain to be defined. It has been proposed that the induction of cellular senescence after injury could amplify neuroinflammation and induce long-term tissue changes. The induction of a senescence response post-injury in the immature brain has yet to be characterised. We carried out two types of brain injury in juvenile CD1 mice: invasive TBI using controlled cortical impact (CCI) and repetitive mild TBI (rmTBI) using weight drop injury. The analysis of senescence-related signals showed an increase in γH2AX-53BP1 nuclear foci, p53, p19ARF, and p16INK4a expression in the CCI group, 5 days post-injury (dpi). At 35 days, the difference was no longer statistically significant. Gene expression showed the activation of different senescence pathways in the ipsilateral and contralateral hemispheres in the injured mice. CCI-injured mice showed a neuroinflammatory early phase after injury (increased Iba1 and GFAP expression), which persisted for GFAP. After CCI, there was an increase at 5 days in p16INK4, whereas in rmTBI, a significant increase was seen at 35 dpi. Both injuries caused a decrease in p21 at 35 dpi. In rmTBI, other markers showed no significant change. The PCR array data predicted the activation of pathways connected to senescence after rmTBI. These results indicate the induction of a complex cellular senescence and glial reaction in the immature mouse brain, with clear differences between an invasive brain injury and a repetitive mild injury. • Cellular senescence could be a critical factor linked to risk of neurodegenerative disease. • Senescence signals can be activated by traumatic injury in the juvenile mouse brain. • Controlled cortical impact and repetitive mild injury trigger different senescence profiles. • Senescence induction occurs in parallel with neuroinflammation. • In the immature brain, as senescence wanes, protective pro-repair mechanisms may be initiated. [ABSTRACT FROM AUTHOR]