ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2003
Formation of complement membrane attack complex in mammalian cerebral cortex evokes seizures and neurodegeneration.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
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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.
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Who cites it
57 citing papers in PubMed, 144 citations in OpenAlex.
- Integrative single-cell and spatial transcriptomics combined with machine learning to discover complement-associated biomarkers in temporal lobe epilepsy with hippocampal sclerosis.Functional & integrative genomics · 2026Article
- 3'-Sialyllactose Prevents Atherosclerosis by Attenuating Chronic Inflammation via the Gut-Immune-Cardiovascular Axis inFood science & nutrition · 2026Article
- Electrophysiologically Targeted Biopsies Reveal the Transcriptional Landscape of Focal Epilepsy.bioRxiv : the preprint server for biology · 2026Article
- Microglial pathological synaptic pruning in epilepsy: pathophysiology and therapeutic potential.Frontiers in immunology · 2026Review
- Smoking Impacts Alzheimer's Disease Progression Through Oral Microbiota Modulation.Molecular neurobiology · 2025Review
- [(Auto)immunity in focal epilepsy: mechanisms of (auto‑)immune-inflammatory epileptogenic neurodegeneration].Der Nervenarzt · 2024Review
- Comparative Proteomic Profiling of Blood Plasma Revealed Marker Proteins Involved in Temporal Lobe Epilepsy.International journal of molecular sciences · 2024Article
- CNS autoimmune response in the MAM/pilocarpine rat model of epileptogenic cortical malformation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Mechanisms of Organophosphate Toxicity and the Role of Acetylcholinesterase Inhibition.Toxics · 2023Review
- Effects of Diclofenac Sodium on Seizure Activity in Rats with Pentylenetetrazole-Induced Convulsions.Neurochemical research · 2023Article
- Liver Transcriptome Analysis Reveals Energy Regulation and Functional Impairment of Onychostoma sima During Starvation.Marine biotechnology (New York, N.Y.) · 2023Article
- Downregulation of oxidative stress-mediated glial innate immune response suppresses seizures in a fly epilepsy model.Cell reports · 2023Article
- Neuroinflammation and status epilepticus: a narrative review unraveling a complex interplay.Frontiers in pediatrics · 2023Review
- Mice deficient in complement C3 are protected against recognition memory deficits and astrogliosis induced by status epilepticus.Frontiers in molecular neuroscience · 2023Article
- Neuroinflammation and Proinflammatory Cytokines in Epileptogenesis.Molecular neurobiology · 2022Review
- Aberrant Complement System Activation in Neurological Disorders.International journal of molecular sciences · 2021Review
- Investigation of the Molecular Mechanisms of Antioxidant Damage and Immune Response Downregulation in Liver ofFrontiers in endocrinology · 2021Article
- The good, the bad, and the opportunities of the complement system in neurodegenerative disease.Journal of neuroinflammation · 2020Review
- Insights into Potential Targets for Therapeutic Intervention in Epilepsy.International journal of molecular sciences · 2020Review
- Precision Medicine in Neurology: The Inspirational Paradigm of Complement Therapeutics.Pharmaceuticals (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The complement system consists of >30 proteins that interact in a carefully regulated manner to destroy invading bacteria and prevent the deposition of immune complexes in normal tissue. This complex system can be activated by diverse mechanisms proceeding through distinct pathways, yet all converge on a final common pathway in which five proteins assemble into a multimolecular complex, the membrane attack complex (MAC). The MAC inserts into cell membranes to form a functional pore, resulting in ion flux and ultimately osmotic lysis. Immunohistochemical evidence of the MAC decorating neurons in cortical gray matter has been identified in multiple CNS diseases, yet the deleterious consequences, if any, of MAC deposition in the cortex of mammalian brain in vivo are unknown. Here we demonstrate that the sequential infusion of individual proteins of the membrane attack pathway (C5b6, C7, C8, and C9) into the hippocampus of awake, freely moving rats induced both behavioral and electrographic seizures as well as cytotoxicity. The onset of seizures occurred during or shortly after the infusion of C8/C9. Neither seizures nor cytotoxicity resulted from the simultaneous infusion of all five proteins premixed in vitro. The requirement for the sequential infusion of all five proteins together with the temporal relationship of seizure onset to infusions of C8/C9 implies that the MAC was formed in vivo and triggered both seizures and cytotoxicity. Deposition of the complement MAC in cortical gray matter may contribute to epileptic seizures and cell death in diverse diseases of the human brain.
Indexed as
Identifiers
12574424PMC6741927W2146768507What 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.