Microglia moonlighting after traumatic brain injury: aging and interferons influence chronic microglia reactivity
Lynde M Wangler1, Jonathan P Godbout2
1Department of Neuroscience, The Ohio State University Wexner Medical Center, 333 W 10th Ave, Columbus, OH, USA.
Abstract:
Most of the individuals who experience traumatic brain injury (TBI) develop neuropsychiatric and cognitive complications that negatively affect recovery and health span. Activation of multiple inflammatory pathways persists after TBI, but it is unclear how inflammation contributes to long-term behavioral and cognitive deficits. One outcome of TBI is microglial priming and subsequent hyper-reactivity to secondary stressors, injuries, or immune challenges that further augment complications. Additionally, microglia priming with aging contributes to exaggerated glial responses to TBI. One prominent inflammatory pathway, interferon (IFN) signaling, is increased after TBI and may contribute to microglial priming and subsequent reactivity. This review discusses the contributions of microglia to inflammatory processes after TBI, as well as the influence of aging and IFNs on microglia reactivity and chronic inflammation after TBI.
Insights
Traumatic brain injury (TBI) can cause lasting cognitive issues due to persistent inflammation. Microglia, immune cells in the brain, become primed after TBI, especially with aging, worsening these long-term effects.
Area of Science:
- Neuroscience
- Immunology
- Neurology
Background:
- Traumatic brain injury (TBI) frequently leads to persistent neuropsychiatric and cognitive deficits, impacting patient recovery and overall health.
- The precise mechanisms by which sustained inflammation after TBI contributes to long-term behavioral and cognitive impairments remain incompletely understood.
- Microglial priming, characterized by hyper-reactivity to subsequent challenges, is a known outcome of TBI and is further exacerbated by aging, leading to exaggerated inflammatory responses.
Purpose of the Study:
- To review the role of microglia in post-TBI inflammatory processes.
- To examine how aging influences microglial reactivity and chronic inflammation following TBI.
- To investigate the contribution of interferon (IFN) signaling to microglial priming and reactivity after TBI.
Main Methods:
- Literature review focusing on microglial activation, inflammation, aging, and interferon signaling in the context of TBI.
- Synthesis of existing research on the molecular and cellular mechanisms underlying chronic neuroinflammation post-TBI.
- Analysis of studies investigating the interplay between aging, IFNs, and microglial responses in TBI models.
Main Results:
- Persistent activation of inflammatory pathways, including interferon signaling, is observed after TBI.
- Microglia become primed post-TBI, exhibiting heightened reactivity to secondary insults, which is amplified by aging.
- Increased interferon signaling is implicated in microglial priming and sustained inflammatory responses, contributing to chronic complications.
Conclusions:
- Microglia play a central role in mediating chronic inflammation after TBI.
- Aging significantly exacerbates microglial reactivity and inflammatory responses to TBI.
- Interferon signaling pathways are key contributors to TBI-induced microglial priming and long-term neuroinflammation.
