Evidence map›Paper›PMID 40643056›Full record

ArticleAdvanced healthcare materials2025

Immunomodulation With Local, Sustained Delivery of Pituitary Adenylate Cyclase Activating Polypeptide Results in Improved Functional Recovery in Stroke-Injured Mice.

Eric Ho, David Xinzheyang Li, Hong Cui, Dania Akbar, Ricky Siu, Cindi M Morshead, David Chatenet, Molly S Shoichet

Abstract read
In one paragraph

Article in Advanced healthcare materials, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

7 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. 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

8 authors.

Eric HoDepartment of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, M5S 3E5, Canada.
David Xinzheyang LiInstitute of Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON, M5S 3G9, Canada.
Hong CuiInstitute of Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON, M5S 3G9, Canada.
Dania AkbarTerrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON, M5S 3E1, Canada.
Ricky SiuInstitute of Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON, M5S 3G9, Canada.
Cindi M MorsheadInstitute of Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON, M5S 3G9, Canada.ORCID https://orcid.org/0000-0003-4605-4883
David ChatenetINRS - Centre Armand-Frappier Santé Biotechnologie, 531 boul. des Prairies, Laval, QC, H7V 1B7, Canada.
Molly S ShoichetDepartment of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, M5S 3E5, Canada.ORCID https://orcid.org/0000-0003-1830-3475

Funding

CIHR CPG-170614Heart and Stroke Foundation G-23-0035038Herzberg Gold Medal GLDSU 537982-20Natural Sciences and Engineering Research Council of Canada CHRP 549672-20NSERC Discovery RGPIN-2019-06933
6 · The paper itself

Abstract

Following ischemic stroke, astrocytes and microglia become activated and create a hostile microenvironment that can exacerbate brain damage, yet these cells also contribute to tissue regeneration. Pituitary adenylate cyclase activating polypeptide (PACAP) is a promising neuroprotective peptide that modulates microglia toward a pro-reparative phenotype, however, its short half-life in vivo and dose-limited off-target effects have made systemic delivery untenable. Local delivery presents a promising alternative. To this end, we developed a hydrogel-nanoparticle composite for the minimally invasive, local delivery of PACAP to the brain and tested this strategy in chemically-induced, endothelin-1 stroke-injured mice. We demonstrate that prolonged delivery of PACAP improved the physical strength and mobility of mice for up to 28 days after stroke. The treatment decreased the number of apoptotic neurons in the stroke microenvironment, increased neuron survival at 28 days post-stroke, and attenuated reactive astrogliosis and microglia activation. PACAP stimulation resulted in increased Iba1

Indexed as

ImmunomodulationPituitary Adenylate Cyclase-Activating PolypeptideRecovery of FunctionStrokeAnimalsAstrocytesHydrogelsMaleMiceMice, Inbred C57BLMicrogliaNanoparticlesNeuronsNeuroprotective AgentsHydrogelsNeuroprotective AgentsPituitary Adenylate Cyclase-Activating Polypeptideastrocyteselectrostatic controlled releasehydrogelinflammationmicrogliananoparticlePACAPpituitary adenylate cyclase activating polypeptidestroke

Identifiers

PMID40643056
PMCPMC12447048

What Socratic 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 Socratic graph.