Evidence map›Paper›PMID 37054778›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2023

Dendrimer-enabled targeted delivery attenuates glutamate excitotoxicity and improves motor function in a rabbit model of cerebral palsy.

Fan Zhang, Zhi Zhang, Jesse Alt, Siva P Kambhampati, Anjali Sharma, Sarabdeep Singh, Elizabeth Nance, Ajit G Thomas, Camilo Rojas, Rana Rais and 3 more

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

Article in Journal of controlled release : official journal of the Controlled Release Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.8field-weighted citation impact, top 14% 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

13 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Drug and nucleic acid delivery and targeting to the brain.Journal of controlled release : official journal of the Controlled Release Society · 2024
    Article
  11. Article
  12. Targeting glutamate carboxypeptidase II in IBD.Advances in pharmacology (San Diego, Calif.) · 2024
    Review
  13. 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

13 authors at 2 institutions in 1 country.

Fan ZhangCenter for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Zhi ZhangAnesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Jesse AltJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Siva P KambhampatiCenter for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Anjali SharmaCenter for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Sarabdeep SinghAnesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Elizabeth NanceAnesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Ajit G ThomasJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Camilo RojasJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Rana RaisJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Barbara S SlusherJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Rangaramanujam M KannanCenter for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Electronic address: krangar1@jhmi.edu.
Sujatha KannanAnesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Electronic address: skannan3@jhmi.edu.
Johns Hopkins University · USJohns Hopkins Medicine · US

Funding

Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI Jiang Qian · 1985 to 2026
$22.1M
Targeting glutamate carboxypeptidase in perinatal brain injuryR01NS093416 · NINDS · JOHNS HOPKINS UNIVERSITY · PI Sujatha Kannan, Kannan Rangaramanujam · 2016 to 2026
$4.8M
NEI NIH HHS P30 EY001765NINDS NIH HHS R01 NS093416
6 · The paper itself

Abstract

Glutamate carboxypeptidase II (GCPII), localized on the surface of astrocytes and activated microglia, regulates extracellular glutamate concentration in the central nervous system (CNS). We have previously shown that GCPII is upregulated in activated microglia in the presence of inflammation. Inhibition of GCPII activity could reduce glutamate excitotoxicity, which may decrease inflammation and promote a 'normal' microglial phenotype. 2-(3-Mercaptopropyl) pentanedioic acid (2-MPPA) is the first GCPII inhibitor that underwent clinical trials. Unfortunately, immunological toxicities have hindered 2-MPPA clinical translation. Targeted delivery of 2-MPPA specifically to activated microglia and astrocytes that over-express GCPII has the potential to mitigate glutamate excitotoxicity and attenuate neuroinflammation. In this study, we demonstrate that 2-MPPA when conjugated to generation-4, hydroxyl-terminated polyamidoamine (PAMAM) dendrimers (D-2MPPA) localize specifically in activated microglia and astrocytes only in newborn rabbits with cerebral palsy (CP), not in controls. D-2MPPA treatment led to higher 2-MPPA levels in the injured brain regions compared to 2-MPPA treatment, and the extent of D-2MPPA uptake correlated with the injury severity. D-2MPPA was more efficacious than 2-MPPA in decreasing extracellular glutamate level in ex vivo brain slices of CP kits, and in increasing transforming growth factor beta 1 (TGF-β1) level in primary mixed glial cell cultures. A single systemic intravenous dose of D-2MPPA on postnatal day 1 (PND1) decreased microglial activation and resulted in a change in microglial morphology to a more ramified form along with amelioration of motor deficits by PND5. These results indicate that targeted dendrimer-based delivery specifically to activated microglia and astrocytes can improve the efficacy of 2-MPPA by attenuating glutamate excitotoxicity and microglial activation.

Indexed as

Cerebral PalsyDendrimersAnimalsBrainGlutamic AcidInflammationMicrogliaRabbitsDendrimersGlutamic Acid2-(3-mercaptopropyl) pentanedioic acidCerebral palsyGlutamate carboxypeptidase IIGlutamate excitotoxicityN-Acetylaspartylglutamic acidPolyamidoamine dendrimer

Identifiers

PMID37054778
PMCPMC10330216
OpenAlexW4365484990

What OpenQuestion holds

Textmetadata
LicenceTDM
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.