Evidence map›Paper›PMID 38635635›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2024

CNS autoimmune response in the MAM/pilocarpine rat model of epileptogenic cortical malformation.

Massimo Costanza, Arianna Ciotti, Alessandra Consonni, Barbara Cipelletti, Alessandro Cattalini, Cinzia Cagnoli, Fulvio Baggi, Marco de Curtis, Francesca Colciaghi

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.6field-weighted citation impact, top 18% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Causal correlation between seizure activity and brain damage.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
    Review
  3. Review
  4. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Massimo Costanza *Neuro-Oncology Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Neurologico Carlo Besta, Milan 20133, Italy.ORCID 0000-0002-1673-8574
Arianna Ciotti *Epilepsy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Neurologico Carlo Besta, Milan 20133, Italy.
Alessandra ConsonniNeuroimmunology Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Neurologico Carlo Besta, Milan 20133, Italy.ORCID 0000-0002-6610-764X
Barbara CipellettiEpilepsy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Neurologico Carlo Besta, Milan 20133, Italy.
Alessandro CattaliniEpilepsy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Neurologico Carlo Besta, Milan 20133, Italy.ORCID 0000-0002-9833-6869
Cinzia CagnoliEpilepsy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Neurologico Carlo Besta, Milan 20133, Italy.ORCID 0000-0001-6863-6687
Fulvio BaggiNeuroimmunology Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Neurologico Carlo Besta, Milan 20133, Italy.ORCID 0000-0002-4618-0102
Marco de CurtisEpilepsy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Neurologico Carlo Besta, Milan 20133, Italy.
Francesca ColciaghiEpilepsy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Neurologico Carlo Besta, Milan 20133, Italy.ORCID 0000-0002-6487-380X
Istituti di Ricovero e Cura a Carattere Scientifico · IT

Funding

Fondazione Italiana Sclerosi Multipla (FISM) 2022/R-Single/051Ministero della Salute (Italy Ministry of Health) RRC 2023 L1.1Ministero della Salute (Italy Ministry of Health) RRC 2023 L2.4Novartis (Novartis AG) #43010
6 · The paper itself

Abstract

The development of seizures in epilepsy syndromes associated with malformations of cortical development (MCDs) has traditionally been attributed to intrinsic cortical alterations resulting from abnormal network excitability. However, recent analyses at single-cell resolution of human brain samples from MCD patients have indicated the possible involvement of adaptive immunity in the pathogenesis of these disorders. By exploiting the MethylAzoxyMethanol (MAM)/pilocarpine (MP) rat model of drug-resistant epilepsy associated with MCD, we show here that the occurrence of status epilepticus and subsequent spontaneous recurrent seizures in the malformed, but not in the normal brain, are associated with the outbreak of a destructive autoimmune response with encephalitis-like features, involving components of both cell-mediated and humoral immune responses. The MP brain is characterized by blood-brain barrier dysfunction, marked and persisting CD8+ T cell invasion of the brain parenchyma, meningeal B cell accumulation, and complement-dependent cytotoxicity mediated by antineuronal antibodies. Furthermore, the therapeutic treatment of MP rats with the immunomodulatory drug fingolimod promotes both antiepileptogenic and neuroprotective effects. Collectively, these data show that the MP rat could serve as a translational model of epileptogenic cortical malformations associated with a central nervous system autoimmune response. This work indicates that a preexisting brain maldevelopment predisposes to a secondary autoimmune response, which acts as a precipitating factor for epilepsy and suggests immune intervention as a therapeutic option to be further explored in epileptic syndromes associated with MCDs.

Indexed as

EpilepsyPilocarpineAnimalsAutoimmunityBrainDisease Models, AnimalHumansMethylazoxymethanol AcetateRatsSeizuresmethylazoxymethanolMethylazoxymethanol AcetatePilocarpinecomplement cascadecortical dysplasiaencephalitisepilepsyneurodegeneration

Identifiers

PMID38635635
PMCPMC11047071
OpenAlexW4394909914

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.