ArticleProceedings of the National Academy of Sciences of the United States of America2015
An anticomplement agent that homes to the damaged brain and promotes recovery after traumatic brain injury in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
53 citing papers in PubMed, 93 citations in OpenAlex.
- Shifting From Systemic to Precision-Targeted Complement Therapies: Opportunities and Hurdles.European journal of immunology · 2026Review
- Complement in Traumatic Brain Injury: Linking Acute Injury to Chronic Neurodegeneration.European journal of immunology · 2026Review
- Knowing the enemy: strategic targeting of complement to treat Alzheimer disease.Nature reviews. Neurology · 2025Review
- Deciphering Proteomic Expression in Inflammatory Disorders: A Mass Spectrometry Exploration Comparing Infectious, Noninfectious, and Traumatic Brain Injuries in Human Cerebrospinal Fluid.Neurotrauma reports · 2024Article
- Voluntary wheel running prevents formation of membrane attack complexes and myelin degradation after peripheral nerve injury.Brain, behavior, and immunity · 2024Article
- A role for P-selectin and complement in the pathological sequelae of germinal matrix hemorrhage.Journal of neuroinflammation · 2023Article
- Mass cytometric analysis of the immune cell landscape after traumatic brain injury elucidates the role of complement and complement receptors in neurologic outcomes.Acta neuropathologica communications · 2023Article
- A Role for P-selectin and Complement in the Pathological Sequelae of Germinal Matrix Hemorrhage.Research square · 2023Article
- Tackling Neuroinflammation After Traumatic Brain Injury: Complement Inhibition as a Therapy for Secondary Injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- Complement activation kindles the transition of acute post-traumatic brain injury to a chronic inflammatory disease.Neural regeneration research · 2022Article
- In utero exposure to maternal anti-aquaporin-4 antibodies alters brain vasculature and neural dynamics in male mouse offspring.Science translational medicine · 2022Article
- Hydroxychloroquine attenuates neuroinflammation following traumatic brain injury by regulating the TLR4/NF-κB signaling pathway.Journal of neuroinflammation · 2022Article
- The Complement System in the Central Nervous System: From Neurodevelopment to Neurodegeneration.Biomolecules · 2022Review
- Neuroinflammation Following Traumatic Brain Injury: Take It Seriously or Not.Frontiers in immunology · 2022Review
- Article
- Complement C3 Aggravates Post-epileptic Neuronal Injury Via Activation of TRPV1.Neuroscience bulletin · 2021Article
- Comparative transcriptomic analysis of ratNeural regeneration research · 2021Article
- Aberrant Complement System Activation in Neurological Disorders.International journal of molecular sciences · 2021Review
- Complement mediates neuroinflammation and cognitive decline at extended chronic time points after traumatic brain injury.Acta neuropathologica communications · 2021Article
- Complement Drives Synaptic Degeneration and Progressive Cognitive Decline in the Chronic Phase after Traumatic Brain Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of complement is a key determinant of neuropathology and disability after traumatic brain injury (TBI), and inhibition is neuroprotective. However, systemic complement is essential to fight infections, a critical complication of TBI. We describe a targeted complement inhibitor, comprising complement receptor of the Ig superfamily (CRIg) fused with complement regulator CD59a, designed to inhibit membrane attack complex (MAC) assembly at sites of C3b/iC3b deposition. CRIg and CD59a were linked via the IgG2a hinge, yielding CD59-2a-CRIg dimer with increased iC3b/C3b binding avidity and MAC inhibitory activity. CD59-2a-CRIg inhibited MAC formation and prevented complement-mediated lysis in vitro. CD59-2a-CRIg dimer bound C3b-coated surfaces with submicromolar affinity (KD). In experimental TBI, CD59-2a-CRIg administered posttrauma homed to sites of injury and significantly reduced MAC deposition, microglial accumulation, mitochondrial stress, and axonal damage and enhanced neurologic recovery compared with placebo controls. CD59-2a-CRIg inhibited MAC-induced inflammasome activation and IL-1β production in microglia. Given the important anti-infection roles of complement opsonization, site-targeted inhibition of MAC should be considered to promote recovery postneurotrauma.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.