Evidence map›Paper›PMID 37150606›Full record

ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2023

Targeting BACE1-mediated production of amyloid beta improves hippocampal synaptic function in an experimental model of ischemic stroke.

Jacob M Basak, Macy Falk, Danae N Mitchell, Kelley A Coakley, Nidia Quillinan, James E Orfila, Paco S Herson

Open access · greenAbstract read
In one paragraph

Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

9 citing papers in PubMed, 13 citations in OpenAlex.

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  9. Recent advances in mechanistic, therapeutic, and diagnostic research of cerebrovascular diseases: updates from brain & BrainPET 2022.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023
    Article
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

7 authors at 2 institutions in 1 country.

Jacob M BasakDepartment of Anesthesiology, University of Colorado Anschutz School of Medicine, Aurora, Colorado, USA.ORCID 0000-0001-9165-0081
Macy FalkDepartment of Anesthesiology, University of Colorado Anschutz School of Medicine, Aurora, Colorado, USA.
Danae N MitchellDepartment of Anesthesiology, University of Colorado Anschutz School of Medicine, Aurora, Colorado, USA.
Kelley A CoakleyDepartment of Neurosurgery, The Ohio State University College of Medicine, Columbus, Ohio, USA.
Nidia QuillinanDepartment of Anesthesiology, University of Colorado Anschutz School of Medicine, Aurora, Colorado, USA.
James E OrfilaDepartment of Neurosurgery, The Ohio State University College of Medicine, Columbus, Ohio, USA.
Paco S HersonDepartment of Neurosurgery, The Ohio State University College of Medicine, Columbus, Ohio, USA.
University of Colorado Anschutz Medical Campus · USThe Ohio State University · US

Funding

Targeting TRPM2 channels to improve synaptic and cognitive function after cerebral ischemiaR01NS092645 · NINDS · UNIVERSITY OF COLORADO DENVER · PI HERSON, PACO S · 2016 to 2020
$1.7M
New approach to sustained neuroprotection and enhanced recovery following acute ischemic strokeRF1NS127413 · NINDS · OHIO STATE UNIVERSITY · PI HERSON, PACO S · 2022 to 2022
$1.7M
Colorado Preparation in Interdisciplinary Knowledge to Excel PREPR25GM140243 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI Eduardo V Davila · 2022 to 2026
$1.6M
New approach to sustained neuroprotection and enhanced recovery following acute ischemic strokeR01NS127413 · NINDS · OHIO STATE UNIVERSITY · PI Paco S Herson · 2025 to 2026
$1.1M
NIGMS NIH HHS R25 GM140243NINDS NIH HHS R01 NS092645NINDS NIH HHS R01 NS127413NINDS NIH HHS RF1 NS127413
6 · The paper itself

Abstract

Post-stroke cognitive impairment and dementia (PSCID) affects many survivors of large vessel cerebral ischemia. The molecular pathways underlying PSCID are poorly defined but may overlap with neurodegenerative pathophysiology. Specifically, synaptic dysfunction after stroke may be directly mediated by alterations in the levels of amyloid beta (Aβ), the peptide that accumulates in the brains of Alzheimer's disease (AD) patients. In this study, we use the transient middle cerebral artery occlusion (MCAo) model in young adult mice to evaluate if a large vessel stroke increases brain soluble Aβ levels. We show that soluble Aβ40 and Aβ42 levels are increased in the ipsilateral hippocampus in MCAo mice 7 days after the injury. We also analyze the level and activity of β-site amyloid precursor protein cleaving enzyme 1 (BACE1), an enzyme that generates Aβ in the brain, and observe that BACE1 activity is increased in the ipsilateral hippocampus of the MCAo mice. Finally, we highlight that treatment of MCAo mice with a BACE1 inhibitor during the recovery period rescues stroke-induced deficits in hippocampal synaptic plasticity. These findings support a molecular pathway linking ischemia to alterations in BACE1-mediated production of Aβ, and encourage future studies that evaluate whether targeting BACE1 activity improves the cognitive deficits seen with PSCID.

Indexed as

Ischemic StrokeStrokeAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAnimalsAspartic Acid EndopeptidasesHippocampusHumansMiceModels, TheoreticalAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAspartic Acid EndopeptidasesBACE1 protein, humanAlzheimer’s diseaseBrain ischemiacognitive impairment/declinehippocampusneurodegeneration

Identifiers

PMID37150606
PMCPMC10638992
OpenAlexW4321496261

What OpenQuestion holds

Textmetadata
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.