ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2021
Complement Drives Synaptic Degeneration and Progressive Cognitive Decline in the Chronic Phase after Traumatic Brain Injury.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Microglia in Post-Traumatic Brain Injury (TBI) Cognitive Impairment: From Pathological Changes to Therapeutic Approaches.CNS neuroscience & therapeutics · 2025Pooled it
- Site-targeted proximal complement C3 inhibition, but not C5 blockade, attenuates neurodegeneration in a mouse model of amyotrophic lateral sclerosis: Implications for failed clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Electroacupuncture Prevents TBI-Induced Synaptic Loss by Inhibiting CaMKII/Drp1-Dependent Mitochondrial Fission.Biomolecules · 2026Article
- Clearance of Early Complement Protein From CSF After Aneurysmal Subarachnoid Hemorrhage and Influence on Neurologic Outcome.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Type I interferon signaling in microglia drives synaptic engulfment and neuronal loss following traumatic brain injury.Research square · 2026Article
- Complement in Traumatic Brain Injury: Linking Acute Injury to Chronic Neurodegeneration.European journal of immunology · 2026Review
- Cognitive loss after brain trauma results from sex-specific activation of synaptic pruning processes.Brain : a journal of neurology · 2026Article
- Roles of Microglia in Synaptogenesis, Synaptic Pruning, and Synaptic Plasticity in Physiological Conditions and Central Nervous System Disorders.Current neuropharmacology · 2026Review
- Targeted complement inhibition ameliorates the pathological and cognitive outcomes in repetitive mild closed head injury.Signal transduction and targeted therapy · 2025Article
- Neural Immunoglobulins Shape Brain Circuits.The European journal of neuroscience · 2025Review
- Proteome Profiling of Serum Reveals Pathological Mechanisms and Biomarker Candidates for Cerebral Small Vessel Disease.Translational stroke research · 2025Article
- Shared Mechanisms in Dementia and Depression: The Modulatory Role of Physical Exercise.Journal of neurochemistry · 2025Review
- Uncovering injury-specific proteomic signatures and neurodegenerative risks in single and repetitive traumatic brain injury.Signal transduction and targeted therapy · 2025Article
- Knowing the enemy: strategic targeting of complement to treat Alzheimer disease.Nature reviews. Neurology · 2025Review
- Neuroinflammation in Alzheimer disease.Nature reviews. Immunology · 2025Review
- Repetitive concussions promote microglia-mediated engulfment of presynaptic excitatory input associated with cognitive dysfunction.Communications biology · 2025Article
- Complement inhibition targets a rich-club within the neuroinflammatory network after stroke to improve radiographic and functional outcomes.Journal of neuroinflammation · 2025Article
- Subregional differences in the hippocampal transcriptomic response after penetrating traumatic brain injury in rats.Frontiers in neurology · 2025Article
- Dynamics of synaptic damage in severe traumatic brain injury revealed by cerebrospinal fluid SNAP-25 and VILIP-1.Journal of neurology, neurosurgery, and psychiatry · 2024Article
- Complement-dependent loss of inhibitory synapses on pyramidal neurons following Toxoplasma gondii infection.Journal of neurochemistry · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Cognitive deficits following traumatic brain injury (TBI) remain a major cause of disability and early-onset dementia, and there is increasing evidence that chronic neuroinflammation occurring after TBI plays an important role in this process. However, little is known about the molecular mechanisms responsible for triggering and maintaining chronic inflammation after TBI. Here, we identify complement, and specifically complement-mediated microglial phagocytosis of synapses, as a pathophysiological link between acute insult and a chronic neurodegenerative response that is associated with cognitive decline. Three months after an initial insult, there is ongoing complement activation in the injured brain of male C57BL/6 mice, which drives a robust chronic neuroinflammatory response extending to both hemispheres. This chronic neuroinflammatory response promotes synaptic degeneration and predicts progressive cognitive decline. Synaptic degeneration was driven by microglial phagocytosis of complement-opsonized synapses in both the ipsilateral and contralateral brain, and complement inhibition interrupted the degenerative neuroinflammatory response and reversed cognitive decline, even when therapy was delayed until 2 months after TBI. These findings provide new insight into our understanding of TBI pathology and its management; and whereas previous therapeutic investigations have focused almost exclusively on acute treatments, we show that all phases of TBI, including at chronic time points after TBI, may be amenable to therapeutic interventions, and specifically to complement inhibition.
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