Evidence map›Paper›PMID 36876481›Full record

ArticleStroke2023

Optogenetic Spreading Depolarizations Do Not Worsen Acute Ischemic Stroke Outcome.

Kazutaka Sugimoto, Joanna Yang, Paul Fischer, Tsubasa Takizawa, Inge A Mulder, Tao Qin, Taylan D Erdogan, Mohammad A Yaseen, Sava Sakadžić, David Y Chung and 1 more

Abstract read
In one paragraph

Article in Stroke, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

  1. Spreading depolarization: A wave that precedes and drives cerebral ischemic cell death-Target for neuroprotection.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. A dangerous liaison: Spreading depolarization and tissue acidification in cerebral ischemia.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2025
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. 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

11 authors.

Kazutaka SugimotoDepartments of Radiology (K.S., J.Y., P.F., T.T., I.A.M., T.Q., T.D.E., D.Y.C., M.A.Y., S.S., C.A.), Massachusetts General Hospital, Harvard Medical School, Boston.ORCID 0000-0002-7666-2620
Joanna YangDepartments of Radiology (K.S., J.Y., P.F., T.T., I.A.M., T.Q., T.D.E., D.Y.C., M.A.Y., S.S., C.A.), Massachusetts General Hospital, Harvard Medical School, Boston.
Paul FischerDepartments of Radiology (K.S., J.Y., P.F., T.T., I.A.M., T.Q., T.D.E., D.Y.C., M.A.Y., S.S., C.A.), Massachusetts General Hospital, Harvard Medical School, Boston.ORCID 0000-0001-7673-8552
Tsubasa TakizawaDepartments of Radiology (K.S., J.Y., P.F., T.T., I.A.M., T.Q., T.D.E., D.Y.C., M.A.Y., S.S., C.A.), Massachusetts General Hospital, Harvard Medical School, Boston.ORCID 0000-0003-2605-7200
Inge A MulderDepartments of Radiology (K.S., J.Y., P.F., T.T., I.A.M., T.Q., T.D.E., D.Y.C., M.A.Y., S.S., C.A.), Massachusetts General Hospital, Harvard Medical School, Boston.
Tao QinDepartments of Radiology (K.S., J.Y., P.F., T.T., I.A.M., T.Q., T.D.E., D.Y.C., M.A.Y., S.S., C.A.), Massachusetts General Hospital, Harvard Medical School, Boston.
Taylan D ErdoganDepartments of Radiology (K.S., J.Y., P.F., T.T., I.A.M., T.Q., T.D.E., D.Y.C., M.A.Y., S.S., C.A.), Massachusetts General Hospital, Harvard Medical School, Boston.
Mohammad A YaseenDepartments of Radiology (K.S., J.Y., P.F., T.T., I.A.M., T.Q., T.D.E., D.Y.C., M.A.Y., S.S., C.A.), Massachusetts General Hospital, Harvard Medical School, Boston.ORCID 0000-0002-4154-152X
Sava SakadžićDepartments of Radiology (K.S., J.Y., P.F., T.T., I.A.M., T.Q., T.D.E., D.Y.C., M.A.Y., S.S., C.A.), Massachusetts General Hospital, Harvard Medical School, Boston.ORCID 0000-0001-6318-1193
David Y ChungDepartments of Radiology (K.S., J.Y., P.F., T.T., I.A.M., T.Q., T.D.E., D.Y.C., M.A.Y., S.S., C.A.), Massachusetts General Hospital, Harvard Medical School, Boston.ORCID 0000-0002-7149-5851
Cenk AyataDepartments of Radiology (K.S., J.Y., P.F., T.T., I.A.M., T.Q., T.D.E., D.Y.C., M.A.Y., S.S., C.A.), Massachusetts General Hospital, Harvard Medical School, Boston.ORCID 0000-0002-3644-6042

Funding

Neuroscience Resident Research ProgramR25NS065743 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI CASH, SYDNEY S, WILLIAMS, ZIV · 2009 to 2023
$11.8M
Institutional Career Development CoreKL2TR002542 · NCATS · HARVARD MEDICAL SCHOOL · PI BREDELLA, MIRIAM ANTOINETTE, RUTKOVE, SEWARD B. · 2018 to 2022
$8.7M
Investigating the Microvascular Mechanisms of O2 Supply-Demand Mismatch in Small Vessel Disease using Novel High-Resolution Optical ImagingR01NS115401 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI AYATA, CENK, SAKADZIC, SAVA · 2020 to 2024
$3.5M
Relating Neuroimmune and Neurovascular Alterations During Alzheimer's Disease ProgressionR01AA027097 · NIAAA · NORTHEASTERN UNIVERSITY · PI YASEEN, MOHAMMAD ABBAS · 2018 to 2022
$2.7M
Two-Photon Microscopy of Oxygen Consumption in the BrainR01NS091230 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI SAKADZIC, SAVA · 2015 to 2019
$2.4M
Two-photon Imaging of Oxygen and Blood Flow in Retinal and Cerebral VasculatureRF1NS121095 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI SAKADZIC, SAVA, SHAHIDI, MAHNAZ · 2021 to 2021
$1.9M
Determinants of Functional Brain Connectivity After Subarachnoid HemorrhageK08NS112601 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI CHUNG, DAVID YOUNG · 2019 to 2023
$1.0M
NCATS NIH HHS KL2 TR002542NIAAA NIH HHS R01 AA027097NINDS NIH HHS K08 NS112601NINDS NIH HHS R01 NS091230NINDS NIH HHS R01 NS115401NINDS NIH HHS R25 NS065743NINDS NIH HHS RF1 NS121095
6 · The paper itself

Abstract

backgroundSpreading depolarizations (SDs) are believed to contribute to injury progression and worsen outcomes in focal cerebral ischemia because exogenously induced SDs have been associated with enlarged infarct volumes. However, previous studies used highly invasive methods to trigger SDs that can directly cause tissue injury (eg, topical KCl) and confound the interpretation. Here, we tested whether SDs indeed enlarge infarcts when induced via a novel, noninjurious method using optogenetics.

methodsUsing transgenic mice expressing channelrhodopsin-2 in neurons (Thy1-ChR2-YFP), we induced 8 optogenetic SDs to trigger SDs noninvasively at a remote cortical location in a noninjurious manner during 1-hour distal microvascular clip or proximal an endovascular filament occlusion of the middle cerebral artery. Laser speckle imaging was used to monitor cerebral blood flow. Infarct volumes were then quantified at 24 or 48 hours.

resultsInfarct volumes in the optogenetic SD arm did not differ from the control arm in either distal or proximal middle cerebral artery occlusion, despite a 6-fold and 4-fold higher number of SDs, respectively. Identical optogenetic illumination in wild-type mice did not affect the infarct volume. Full-field laser speckle imaging showed that optogenetic stimulation did not affect the perfusion in the peri-infarct cortex.

conclusionsAltogether, these data show that SDs induced noninvasively using optogenetics do not worsen tissue outcomes. Our findings compel a careful reexamination of the notion that SDs are causally linked to infarct expansion.

Indexed as

Brain IschemiaCortical Spreading DepressionIschemic StrokeStrokeAnimalsInfarction, Middle Cerebral ArteryMiceMice, TransgenicOptogeneticschannelrhodopsinsinfarctionischemic strokemiddle cerebral arteryoptogenetics

Identifiers

PMID36876481
PMCPMC10050120

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.