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Initiation site of experimentally-evoked spreading depolarizations influence tissue outcomes in a murine stroke model.

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Τίτλος: Initiation site of experimentally-evoked spreading depolarizations influence tissue outcomes in a murine stroke model.
Συγγραφείς: Bennett MC; Department of Neurosciences, University of New Mexico, Albuquerque, NM 87131, USA. Electronic address: michael.bennett@umontreal.ca., Morton RA; Department of Neurosciences, University of New Mexico, Albuquerque, NM 87131, USA. Electronic address: ramorton@salud.unm.edu., Carlson AP; Department of Neurosurgery, University of Virginia, Charlottesville, VA 22903, USA. Electronic address: EQB2TS@uvahealth.org., Shuttleworth CW; Department of Neurosciences, University of New Mexico, Albuquerque, NM 87131, USA. Electronic address: bshuttleworth@salud.unm.edu.
Πηγή: Experimental neurology [Exp Neurol] 2026 May; Vol. 399, pp. 115671. Date of Electronic Publication: 2026 Jan 27.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Academic Press Country of Publication: United States NLM ID: 0370712 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2430 (Electronic) Linking ISSN: 00144886 NLM ISO Abbreviation: Exp Neurol Subsets: MEDLINE
Imprint Name(s): Publication: Orlando Fl : Academic Press
Original Publication: New York.
Ιατρικοί όροι (MeSH): Cortical Spreading Depression*/physiology , Stroke*/physiopathology , Stroke*/pathology , Infarction, Middle Cerebral Artery*/physiopathology , Infarction, Middle Cerebral Artery*/pathology, Potassium Chloride/toxicity ; Animals ; Male ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL ; Optogenetics
Περίληψη: Spreading depolarization waves (SDs) are implicated in secondary expansion of brain injuries and are the target for initial clinical intervention trials. However, the assumption that SD directly causes neuronal injury has been challenged by recent findings with experimentally-induced SD in stroke models. The current study addressed this controversy by examining whether stroke consequences are confounded by the precise location of experimental SD initiation. Focal ischemic lesions were generated by transient distal middle cerebral artery occlusion in male mice. Clusters of SDs (6 at 10-min intervals) were induced by either focal KCl application or optogenetic stimulation during occlusion. SDs were initiated either in regions close to the infarct core (penumbral-SD; <50% perfusion) or in less compromised tissue in the same hemisphere (remote-SD; >70% perfusion). Despite the fact that all SDs fully invaded stroke expansion areas, the location of experimental SD induction had significant effects on stroke outcomes measured 48 h after reperfusion. Penumbral-SDs resulted in larger infarct expansion than seen in control stroke mice lacking experimentally-imposed SD. Conversely, remote-SDs led to significantly smaller infarcts than stroke alone. Laser speckle contrast imaging of blood flow in injury expansion areas showed enhanced hypoperfusion responses after penumbral-SDs and larger hyperemic responses after remote-SDs, suggesting that differential vascular responses could contribute to stroke outcomes. Overall, this study helps to reconcile different prior reports by showing that experimentally-induced SDs can either exacerbate or reduce stroke-induced injury depending on the SD initiation site and further strengthens evidence for injurious roles of SDs initiating in vulnerable brain tissue.
(Copyright © 2026 The Authors. Published by Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Σχόλια: Update of: bioRxiv. 2025 Oct 06:2025.10.03.680372. doi: 10.1101/2025.10.03.680372.. (PMID: 41279059)
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Grant Information: P30 GM159568 United States GM NIGMS NIH HHS; P20 GM109089 United States GM NIGMS NIH HHS; F31 NS129351 United States NS NINDS NIH HHS; R01 NS106901 United States NS NINDS NIH HHS; R01 NS128006 United States NS NINDS NIH HHS
Contributed Indexing: Keywords: Cortical spreading depression; Ischemic stroke; MCAo; Neuronal injury; Optogenetic
Substance Nomenclature: 660YQ98I10 (Potassium Chloride)
Entry Date(s): Date Created: 20260129 Date Completed: 20260701 Latest Revision: 20260920
Update Code: 20260920
PubMed Central ID: PMC12910855
DOI: 10.1016/j.expneurol.2026.115671
PMID: 41611073
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1090-2430
DOI:10.1016/j.expneurol.2026.115671