Responses of Central Microglial Cells and Ganglionic Macrophages to Peripheral Injury and Disease
Bibliographic record
Abstract
Microglial cells in the brain and spinal cord are exquisitely sensitive to injury and disease, responding by activation that results in changes of morphology and function. These cells are also responsive to trauma/inflammation in peripheral targets, such that injury or disease of motor, sensory and/or autonomic fibers can result in robust activation of microglia centrally. This activation of microglia triggers the presentation of phenotypes that resembles cells with macrophage‐like properties (i.e., increased cytokine production). Curiously, resident macrophages in peripheral neural tissues (e.g., nerves and ganglia) display many similar morphological and functional properties of central microglia. We have used a number of injury paradigms to assess the activation of central microglial cells and peripheral macrophages, as a consequence of direct or indirect neural damage. These experimental models include i) unilateral partial sciatic nerve ligation (a model of peripheral nerve damage), ii) unilateral injection of monosodium‐iodoacetate (MIA) into the hind limb footpad (a model of cutaneous/joint inflammation), and dextran sodium sulfate (DSS) in the drinking water (a model of colonic inflammation). We have also assessed the activation of central microglial cells and peripheral macrophages in aging models (i.e., NGF transgenic mice and TgCRND8 mice). The transmembrane p75 neurotrophin receptor (p75NTR) binds with comparable affinity to neurotrophins (e.g., nerve growth factor, NGF) and cytokines (e.g., tumor necrosis factor alpha, TNFα). Both neurotrophins and cytokines have been implicated in the pathophysiological features of sensory neuron dysfunction as a consequence of injury, disease, and aging. For instance, following peripheral nerve damage, macrophages (i.e., resident and/or infiltrating blood‐borne) in the associated dorsal root ganglia (DRG) display increased process extension, which is indicative of activation. Central microglial cells act in kind. Our studies have sought to determine whether the expression of p75NTR in adult mice affects the activation of microglial cells in the spinal cord and macrophages in sensory ganglia after peripheral nerve/tissue injury. Effects we have measured in p75NTR‐deficient mice are curious because central microglial cells and peripheral macrophages (damaged or otherwise) do not express p75NTR. Since target tissue damage and/or inflammation can stimulate increased p75NTR levels by ganglionic glial cells (i.e., satellite and Schwann cells), we have speculated that such glial expression of p75NTR plays a role in the activation of central microglial cells and peripheral macrophages. One possible mechanism may be through p75NTR‐mediated sequestration of increased levels of neurotrophins and/or cytokines by glial cells, thereby minimizing microglia/macrophage activation in mice following injury and inflammation. Support or Funding Information Queen's University
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".