Evidence map›Paper›PMID 41787472›Full record

ArticleCNS neuroscience & therapeutics2026

Restricting Synaptotagmin-3 Internalization Mitigates Cerebral Ischemia/Reperfusion Injury by Curtailed Neuronal Apoptosis and Microglial Re-Programming.

Hua Xu, Hongbo Mi, Rong Cheng, Tiantian Gui, Fangzhou Hu, Yi Yang, Jian Cheng, Qun Xue

Abstract read
In one paragraph

Article in CNS neuroscience & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Hua XuDepartment of Neurology, First Affiliated Hospital of Soochow University, Suzhou, China.ORCID 0000-0001-9253-4357
Hongbo MiJiangsu Key Laboratory of Neuropsychiatric Diseases & College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
Rong ChengJiangsu Key Laboratory of Neuropsychiatric Diseases & College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
Tiantian GuiDepartment of Neurology, First Affiliated Hospital of Soochow University, Suzhou, China.
Fangzhou HuDepartment of Neurology, First Affiliated Hospital of Soochow University, Suzhou, China.
Yi YangDepartment of Pathology, Jintan Affiliated Hospital of Jiangsu University, Changzhou Jintan First People's Hospital, Changzhou, China.
Jian ChengJiangsu Key Laboratory of Neuropsychiatric Diseases & College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
Qun XueDepartment of Neurology, First Affiliated Hospital of Soochow University, Suzhou, China.

Funding

Changzhou Health and Youth Talent Training Project CZQM2023029Changzhou Sci & Tech Program CJ20220001Changzhou Sci & Tech Program CJ20253002Medical Education Collaborative Innovation Fund of Jiangsu University JDYY2023044National Natural Science Foundation of China 82371365
6 · The paper itself

Abstract

aimsIschemic stroke is a major global cause of disability and death. Synaptotagmin-3 (Syt3), a synaptic calcium sensor, exacerbates ischemic injury by promoting pathological glutamate release. This study investigated the potential neuroprotective effect of restriction of Syt3 internalization on neuronal apoptosis and microglial reprogramming following ischemia/reperfusion (I/R).

methodsThe effects of Tat-GluA2-3Y (3Y), a cell-permeable peptide inhibitor of Syt3 internalization, were studied in a mouse model of middle cerebral artery occlusion/reperfusion (MCAO/R) and in oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT22 and BV2 cells.

resultsThe peptide 3Y treatment significantly reduced infarct volume, brain edema, and improved neurological deficits. Additionally, it reduced neuronal apoptosis and also inhibited neuroinflammation by down-regulating the level of IL-1b, TNF-a, and iNOS but up-regulating the level of TGF-b1 and Arg-1. Single-nucleus RNA sequencing of the peri-infarct region revealed a dual mechanism: 3Y suppressed pro-apoptotic gene programs in neurons and facilitated the transformation between different phenotypes of microglia via the cAMP pathway from a pro-inflammatory to an anti-inflammatory and immune-protective state. In vitro, 3Y attenuated oxygen-glucose deprivation-induced neuronal death and instructed microglia to adopt a protective, TGF-β1-secreting phenotype.

conclusionsCollectively, our findings establish the inhibition of Syt3 internalization as a novel therapeutic strategy that concurrently protects neurons and reprograms the microglial immune response, offering a promising dual-mechanism approach for acute stroke therapy.

Indexed as

ApoptosisBrain IschemiaMicrogliaNeuronsReperfusion InjurySynaptotagminsAnimalsCell LineInfarction, Middle Cerebral ArteryMaleMiceMice, Inbred C57BLNeuroprotective AgentsNeuroprotective AgentsSynaptotagminsapoptosiscerebral ischemia/reperfusion injurymicroglial reprogrammingneuroinflammationneuroprotectionSynaptotagmin‐3

Identifiers

PMID41787472
PMCPMC12963021

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.