ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
CCR2 antagonism alters brain macrophage polarization and ameliorates cognitive dysfunction induced by traumatic brain injury.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers.
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Who cites it
155 citing papers in PubMed, 265 citations in OpenAlex.
- GPR84 and Neuroinflammation: A Receptor Worth Targeting, or A Target Worth Reconsidering?Molecular neurobiology · 2026Review
- Infiltrating Monocyte Fate Switch in Retinal Degeneration: From Early Pathology to Late Homeostasis.Research square · 2026Article
- The role of persistent inflammation in failed recovery after perinatal brain injury: is resolution the cure?Journal of neuroinflammation · 2026Review
- Infiltrating monocytes augment alternative complement activation and exacerbate inherited retinal degeneration in a mouse model.Research square · 2026Article
- Temporal and Spatial Patterns of Glial Activation After Unilateral Cortical Injury in Rats.Life (Basel, Switzerland) · 2026Article
- The NOX2-ROS-NLRP3 inflammasome axis in traumatic brain injury.Journal of neuroinflammation · 2025Article
- Inhibition of autophagy-lysosomal function exacerbates microglial and monocyte lipid metabolism reprograming and dysfunction after brain injury.Research square · 2025Article
- Fate mapping of peripherally-derived macrophages after traumatic brain injury in mice reveals a long-lasting population with a distinct transcriptomic signature.Nature communications · 2025Article
- Inhibition of autophagy-lysosomal function exacerbates microglial and monocyte lipid metabolism reprograming and dysfunction after brain injury.bioRxiv : the preprint server for biology · 2025Article
- Chemokines as therapeutic targets for multiple sclerosis: a spatial and chronological perspective.Frontiers in immunology · 2025Review
- Traumatic brain injury and post-injury sleep fragmentation differentially alter the microglial transcriptome.Frontiers in immunology · 2025Article
- P75NTR blockading inhibits Trem2+ M1 phenotype microglia activation and myelin damage following mild traumatic brain injury.Frontiers in neuroscience · 2025Article
- Blood Levels of Dendritic Cell Populations in Patients with Moderate to Severe Traumatic Brain Injury.Neurotrauma reports · 2025Article
- Neuroinflammatory mechanisms may help identify candidate biomarkers in chronic traumatic encephalopathy (CTE).Free neuropathology · 2025Review
- Remote Ischemic Post-Conditioning (RIC) Mediates Anti-Inflammatory Signaling via Myeloid AMPKα1 in Murine Traumatic Optic Neuropathy (TON).International journal of molecular sciences · 2024Article
- Clinical features, cerebrospinal fluid changes, and prognosis in Chinese patients with autoimmune encephalitis.Acta neurologica Belgica · 2024Article
- Modulation of microglia activation by the ascorbic acid transporter SVCT2.Brain, behavior, and immunity · 2024Article
- The contribution of the meningeal immune interface to neuroinflammation in traumatic brain injury.Journal of neuroinflammation · 2024Review
- Microglial histone deacetylase 2 is dispensable for functional and histological outcomes in a mouse model of traumatic brain injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Fibrin promotes oxidative stress and neuronal loss in traumatic brain injury via innate immune activation.Journal of neuroinflammation · 2024Article
95 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Traumatic brain injury (TBI) is a major risk factor for the development of multiple neurodegenerative diseases. With respect to the increasing prevalence of TBI, new therapeutic strategies are urgently needed that will prevent secondary damage to primarily unaffected tissue. Consistently, neuroinflammation has been implicated as a key mediator of secondary damage following the initial mechanical insult. Following injury, there is uncertainty regarding the role that accumulating CCR2(+) macrophages play in the injury-induced neuroinflammatory sequelae and cognitive dysfunction. Using CX3CR1(GFP/+)CCR2(RFP/+) reporter mice, we show that TBI initiated a temporally restricted accumulation of peripherally derived CCR2(+) macrophages, which were concentrated in the hippocampal formation, a region necessary for learning and memory. Multivariate analysis delineated CCR2(+) macrophages' neuroinflammatory response while identifying a novel therapeutic treatment window. As a proof of concept, targeting CCR2(+) macrophages with CCX872, a novel Phase I CCR2 selective antagonist, significantly reduced TBI-induced inflammatory macrophage accumulation. Concomitantly, there was a significant reduction in multiple proinflammatory and neurotoxic mediators with this treatment paradigm. Importantly, CCR2 antagonism resulted in a sparing of TBI-induced hippocampal-dependent cognitive dysfunction and reduced proinflammatory activation profile 1 month after injury. Thus, therapeutically targeting the CCR2(+) subset of monocytes/macrophages may provide a new avenue of clinical intervention following TBI.
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