Evidence map›Paper›PMID 24967312›Full record

ArticleISRN neuroscience2014

An Immunological Approach to Increase the Brain's Resilience to Insults.

En-Ju D Lin, C Wymond Symes, Andrea Townsend-Nicholson, Matthias Klugmann, Claudia B Klugmann, Klaus Lehnert, Dahna Fong, Deborah Young, Matthew J During

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ISRN neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact, top 87% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. Review
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 2 institutions in 3 countries.

En-Ju D LinFunctional Genomics and Translational Neuroscience Lab, Department of Molecular Medicine and Pathology, University of Auckland 85 Park Road, Grafton, Auckland 1142, New Zealand ; Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, BRT 912, 460 W 12th Avenue, Columbus, OH 43210, USA.
C Wymond SymesFunctional Genomics and Translational Neuroscience Lab, Department of Molecular Medicine and Pathology, University of Auckland 85 Park Road, Grafton, Auckland 1142, New Zealand.
Andrea Townsend-NicholsonDepartment of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK.ORCID 0000-0002-7250-2208
Matthias KlugmannFunctional Genomics and Translational Neuroscience Lab, Department of Molecular Medicine and Pathology, University of Auckland 85 Park Road, Grafton, Auckland 1142, New Zealand.ORCID 0000-0003-0574-612X
Claudia B KlugmannFunctional Genomics and Translational Neuroscience Lab, Department of Molecular Medicine and Pathology, University of Auckland 85 Park Road, Grafton, Auckland 1142, New Zealand.
Klaus LehnertViaLactia Biosciences (NZ) Ltd, UNISYS House, 650 Great South Road, Penrose, Auckland 1061, New Zealand.ORCID 0000-0003-4598-4966
Dahna FongFunctional Genomics and Translational Neuroscience Lab, Department of Molecular Medicine and Pathology, University of Auckland 85 Park Road, Grafton, Auckland 1142, New Zealand.ORCID 0000-0003-3988-925X
Deborah YoungFunctional Genomics and Translational Neuroscience Lab, Department of Molecular Medicine and Pathology, University of Auckland 85 Park Road, Grafton, Auckland 1142, New Zealand.
Matthew J DuringFunctional Genomics and Translational Neuroscience Lab, Department of Molecular Medicine and Pathology, University of Auckland 85 Park Road, Grafton, Auckland 1142, New Zealand ; Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, BRT 912, 460 W 12th Avenue, Columbus, OH 43210, USA.
University of Auckland · NZUniversity College London · GB

Funding

Somatic Cell Gene Transfer/Neurological & Clinical ApplicationsR01NS044576 · NINDS · WEILL MEDICAL COLLEGE OF CORNELL UNIV · PI LIN, EN-JU · 2004 to 2013
$3.3M
NINDS NIH HHS R01 NS044576
6 · The paper itself

Abstract

We have previously demonstrated the therapeutic potential of inducing a humoral response with autoantibodies to the N-methyl D-aspartate (NMDA) receptor using a genetic approach. In this study, we generated three recombinant proteins to different functional domains of the NMDA receptor, which is implicated in mediating brain tolerance, specifically NR1[21-375], NR1[313-619], NR1[654-800], and an intracellular scaffolding protein, Homer1a, with a similar anatomical expression pattern. All peptides showed similar antigenicity and antibody titers following systemic vaccination, and all animals thrived. Two months following vaccination, rats were administered the potent neurotoxin, kainic acid. NR1[21-375] animals showed an antiepileptic phenotype but no neuroprotection. Remarkably, despite ineffective antiepileptic activity, 6 of 7 seizing NR1[654-800] rats showed absolutely no injury with only minimal changes in the remaining animal, whereas the majority of persistently seizing rats in the other groups showed moderate to severe hippocampal injury. CREB, BDNF, and HSP70, proteins associated with preconditioning, were selectively upregulated in the hippocampus of NR1[654-800] animals, consistent with the observed neuroprotective phenotype. These results identify NR1 epitopes important in conferring anticonvulsive and neuroprotective effects and support the concept of an immunological strategy to induce a chronic state of tolerance in the brain.

Identifiers

PMID24967312
PMCPMC4045558
OpenAlexW2072343650

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.