ArticleActa neuropathologica communications2021
Complement mediates neuroinflammation and cognitive decline at extended chronic time points after traumatic brain injury.
Article in Acta neuropathologica communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 56 citations in OpenAlex.
- 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
- Neuropathic pain in traumatic brain injury: consequences, mechanisms, and therapeutic avenues.Inflammopharmacology · 2026Review
- Complement in Traumatic Brain Injury: Linking Acute Injury to Chronic Neurodegeneration.European journal of immunology · 2026Review
- Berberine Alleviates Lipopolysaccharide-Induced Impairments in Neuroplasticity and Spatial Memory by Modulating Microglial Polarization via MAPK Signaling Inhibition.Neural plasticity · 2026Article
- Targeted complement inhibition ameliorates the pathological and cognitive outcomes in repetitive mild closed head injury.Signal transduction and targeted therapy · 2025Article
- Complement inhibition targets a rich-club within the neuroinflammatory network after stroke to improve radiographic and functional outcomes.Journal of neuroinflammation · 2025Article
- Relationship between glymphatic system dysfunction and cognitive impairment in patients with mild-to-moderate chronic traumatic brain injury: an analysis of the analysis along the perivascular space (ALPS) index.Quantitative imaging in medicine and surgery · 2024Article
- Acute depletion of complement C3 with cobra venom factor attenuates memory deficits induced by status epilepticus.Epilepsia open · 2024Article
- Immunity impacts cognitive deficits across neurological disorders.Journal of neurochemistry · 2024Review
- Complement propagates visual system pathology following traumatic brain injury.Journal of neuroinflammation · 2024Article
- Pathophysiology-Based Management of Secondary Injuries and Insults in TBI.Biomedicines · 2024Review
- p17/C18-ceramide-mediated mitophagy is an endogenous neuroprotective response in preclinical and clinical brain injury.PNAS nexus · 2024Article
- Microglia moonlighting after traumatic brain injury: aging and interferons influence chronic microglia reactivity.Trends in neurosciences · 2023Review
- Correlation of serum complement factor 5a level with inflammatory response and cognitive function in patients with Alzheimer's disease of different severity.BMC neurology · 2023Article
- Inhibition of complement C3 signaling ameliorates locomotor and visual dysfunction in autoimmune inflammatory diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- A role for P-selectin and complement in the pathological sequelae of germinal matrix hemorrhage.Journal of neuroinflammation · 2023Article
- Complement Drives Chronic Inflammation and Progressive Hydrocephalus in Murine Neonatal Germinal Matrix Hemorrhage.International journal of molecular sciences · 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
- Tandem Mass Tag-based proteomics analysis reveals the vital role of inflammation in traumatic brain injury in a mouse model.Neural regeneration research · 2023Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Traumatic brain injury (TBI) can result in progressive cognitive decline occurring for years after the initial insult, and for which there is currently no pharmacological treatment. An ongoing chronic inflammatory response after TBI is thought to be an important factor in driving this cognitive decline. Here, we investigate the role of complement in neuroinflammation and cognitive decline for up to 6 months after murine TBI. Male C57BL/6 mice were subjected to open head injury using a controlled cortical impact device. At 2 months post TBI, mice were moved to large cages with an enriched environment to simulate rehabilitation therapy, and assigned to one of three treatment groups: 1. vehicle (PBS), 2. CR2Crry (3 doses over 1 week), 3. CR2Crry (continuous weekly dose until the end of the study). The study was terminated at 6 months post-TBI for all groups. Motor and cognitive function was analyzed, with histopathological analysis of brain tissue. Measured at 6 months after TBI, neither of the complement inhibition paradigms improved motor performance. However, mice receiving continuous CR2Crry treatment showed improved spatial learning and memory compared to both mice receiving only 3 doses and to mice receiving vehicle control. Analysis of brain sections at 6 months after injury revealed ongoing complement activation in the control group, with reduced complement activation and C3 deposition in the continuous CR2Crry treatment group. The ipsilateral hemisphere of continuously treated animals also showed a decrease in microglia/macrophage and astrocyte activation compared to vehicle. There was also increased astrocytosis in the contralateral hippocampus of vehicle treated vs. naïve mice, which was reduced in mice continuously treated with CR2Crry. This study demonstrates continued complement mediated neuroinflammation at extended chronic time points after TBI, and extends the potential treatment window for complement inhibition, which has previously been shown to improve outcomes after murine TBI.
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