ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2020
Serial Systemic Injections of Endotoxin (LPS) Elicit Neuroprotective Spinal Cord Microglia through IL-1-Dependent Cross Talk with Endothelial Cells.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Microglia and border-associated macrophages play opposite roles in cerebrovascular and leukocyte responses under systemic inflammation in male mice.Nature communications · 2026Article
- Microglia and neuroinflammation: An in-depth analysis from functional diversity to disease mechanisms.Clinical and translational medicine · 2026Review
- Astrocyte-microglia crosstalk via CSF1 and IFN-β promotes central nervous system repair.Cell reports · 2026Article
- Article
- Orchestrating neuroinflammation: A symphony of Interleukin-1 and cell type-specific Interleukin-1 receptor type 1 signaling in the brain.Brain behavior and immunity integrative · 2026Article
- Is TREM2 a Stretch: Implications of TREM2 Along Spinal Cord Circuits in Health, Aging, Injury, and Disease.Cells · 2025Review
- Evolving insights on the role of microglia in neuroinflammation, plasticity, and regeneration of the injured spinal cord.Frontiers in immunology · 2025Review
- Endothelial cells and macrophages as allies in the healthy and diseased brain.Acta neuropathologica · 2024Review
- Interleukin-1beta and inflammasome expression in spinal cord following chronic constriction injury in male and female rats.Brain, behavior, and immunity · 2024Article
- The secretome of macrophages has a differential impact on spinal cord injury recovery according to the polarization protocol.Frontiers in immunology · 2024Article
- Temporal changes of spinal microglia in murine models of neuropathic pain: a scoping review.Frontiers in immunology · 2024Article
- IL-1R1 signaling in TBI: assessing chronic impacts and neuroinflammatory dynamics in a mouse model of mild closed-head injury.Journal of neuroinflammation · 2023Article
- Systemic Inflammation Leads to Changes in the Intracellular Localization of KLK6 in Oligodendrocytes in Spinal Cord White Matter.Neurochemical research · 2023Article
- Effect of multifactorial therapeutic approach on axonal regeneration and cell viability in an in-vitro model of spinal-derived neural injury.Cell and tissue banking · 2023Article
- Microglial Cytokines Mediate Plasticity Induced by 10 Hz Repetitive Magnetic Stimulation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- The alarmin interleukin-1α triggers secondary degeneration through reactive astrocytes and endothelium after spinal cord injury.Nature communications · 2022Article
- Microglia coordinate cellular interactions during spinal cord repair in mice.Nature communications · 2022Article
- Microglia maintain the normal structure and function of the hippocampal astrocyte network.Glia · 2022Article
- The Role of Microglia in Neuroinflammation of the Spinal Cord after Peripheral Nerve Injury.Cells · 2022Review
- Ischemic Preconditioning Modulates the Peripheral Innate Immune System to Promote Anti-Inflammatory and Protective Responses in Mice Subjected to Focal Cerebral Ischemia.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Microglia are dynamic immunosurveillance cells in the CNS. Whether microglia are protective or pathologic is context dependent; the outcome varies as a function of time relative to the stimulus, activation state of neighboring cells in the microenvironment or within progression of a particular disease. Although brain microglia can be "primed" using bacterial lipopolysaccharide (LPS)/endotoxin, it is unknown whether LPS delivered systemically can also induce neuroprotective microglia in the spinal cord. Here, we show that serial systemic injections of LPS (1 mg/kg, i.p., daily) for 4 consecutive days (LPSx4) consistently elicit a reactive spinal cord microglia response marked by dramatic morphologic changes, increased production of IL-1, and enhanced proliferation without triggering leukocyte recruitment or overt neuropathology. Following LPSx4, reactive microglia frequently contact spinal cord endothelial cells. Targeted ablation or selective expression of IL-1 and IL-1 receptor (IL-1R) in either microglia or endothelia reveal that IL-1-dependent signaling between these cells mediates microglia activation. Using a mouse model of ischemic spinal cord injury in male and female mice, we show that preoperative LPSx4 provides complete protection from ischemia-induced neuron loss and hindlimb paralysis. Neuroprotection is partly reversed by either pharmacological elimination of microglia or selective removal of IL-1R in microglia or endothelia. These data indicate that spinal cord microglia are amenable to therapeutic reprogramming via systemic manipulation and that this potential can be harnessed to protect the spinal cord from injury.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.