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Microglial process convergence onto injured axonal swellings, a human postmortem brain tissue study
Amanda L Logan-Wesley1, Karen M Gorse1, Audrey D Lafrenaye2
1Virginia Commonwealth University, BOX 980709, Richmond, VA, 23298, USA.
Abstract:
Traumatic brain injury (TBI) affects millions globally, with a majority of TBI cases being classified as mild, in which diffuse pathologies prevail. Two of the pathological hallmarks of TBI are diffuse axonal injury (DAI) and microglial activation. While progress has been made investigating the breadth of TBI-induced axonal injury and microglial changes in rodents, the neuroinflammatory progression and interaction between microglia and injured axons in humans is less well understood. Our group previously investigated microglial process convergence (MPC), in which processes of non-phagocytic microglia directly contact injured proximal axonal swellings, in rats and micropigs acutely following TBI. These studies demonstrated that MPC occurred on injured axons in the micropig, but not in the rat, following diffuse TBI. While it has been shown that microglia co-exist and interact with injured axons in humans post-TBI, the occurrence of MPC has not been quantitatively measured in the human brain. Therefore, in the current study we sought to validate our pig findings in human postmortem tissue. We investigated MPC onto injured axonal swellings and intact myelinated fibers in cases from individuals with confirmed DAI and control human brain tissue using multiplex immunofluorescent histochemistry. We found an increase in MPC onto injured axonal swellings, consistent with our previous findings in micropigs, indicating that MPC is a clinically relevant phenomenon that warrants further investigation.
Insights
Microglial process convergence (MPC) occurs on injured axons in humans following traumatic brain injury (TBI). This finding in human brain tissue supports previous observations in micropigs, highlighting MPC as a relevant phenomenon in TBI research.
Area of Science:
- Neuroscience
- Neuropathology
- Traumatic Brain Injury Research
Background:
- Traumatic brain injury (TBI) impacts millions globally, often resulting in mild injuries with diffuse pathologies.
- Diffuse axonal injury (DAI) and microglial activation are key pathological hallmarks of TBI.
- Human neuroinflammation and microglia-injured axon interactions post-TBI remain less understood compared to animal models.
Purpose of the Study:
- To quantitatively measure microglial process convergence (MPC) in human postmortem brain tissue.
- To validate previous findings of MPC in micropigs in the context of human DAI.
- To investigate the occurrence of MPC on injured axonal swellings and intact myelinated fibers in human TBI cases.
Main Methods:
- Utilized multiplex immunofluorescent histochemistry on human postmortem brain tissue.
- Examined cases with confirmed diffuse axonal injury (DAI) and control brain tissue.
- Quantitatively assessed microglial process convergence (MPC) onto injured axonal swellings and intact fibers.
Main Results:
- Observed an increase in microglial process convergence (MPC) onto injured axonal swellings in human TBI cases.
- Findings are consistent with previous studies in micropigs, suggesting conserved biological mechanisms.
- MPC was investigated in relation to both DAI and intact myelinated fibers.
Conclusions:
- Microglial process convergence (MPC) is a measurable phenomenon in the human brain following traumatic brain injury (TBI).
- MPC on injured axons in humans validates prior findings in micropigs.
- MPC represents a clinically relevant pathological feature of TBI warranting further investigation.
