Document Detail


Recurrent spontaneous spreading depolarizations facilitate acute dendritic injury in the ischemic penumbra.
MedLine Citation:
PMID:  20660268     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Spontaneous spreading depolarizations (SDs) occur in the penumbra surrounding ischemic core. These SDs, often referred to as peri-infarct depolarizations, cause vasoconstriction and recruitment of the penumbra into the ischemic core in the critical first hours after focal ischemic stroke; however, the real-time spatiotemporal dynamics of SD-induced injury to synaptic circuitry in the penumbra remain unknown. A modified cortical photothrombosis model was used to produce a square-shaped lesion surrounding a penumbra-like "area at risk" in middle cerebral artery territory of mouse somatosensory cortex. Lesioning resulted in recurrent spontaneous SDs. In vivo two-photon microscopy of green fluorescent protein-expressing neurons in this penumbra-like area at risk revealed that SDs were temporally correlated with rapid (<6 s) dendritic beading. Dendrites quickly (<3 min) recovered between SDs to near-control morphology until the occurrence of SD-induced terminal dendritic injury, signifying acute synaptic damage. SDs are characterized by a breakdown of ion homeostasis that can be recovered by ion pumps if the energy supply is adequate. Indeed, the likelihood of rapid dendritic recovery between SDs was correlated with the presence of nearby flowing blood vessels, but the presence of such vessels was not always sufficient for rapid dendritic recovery, suggesting that energy needs for recovery exceeded energy supply of compromised blood flow. We propose that metabolic stress resulting from recurring SDs facilitates acute injury at the level of dendrites and dendritic spines in metabolically compromised tissue, expediting penumbral recruitment into the ischemic core.
Authors:
W Christopher Risher; Deborah Ard; Jianghe Yuan; Sergei A Kirov
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  30     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-27     Completed Date:  2010-08-13     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9859-68     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain Ischemia / pathology,  physiopathology*,  ultrasonography*
Cerebrovascular Circulation
Cortical Spreading Depression*
Dendrites / metabolism*,  ultrasonography*
Dendritic Spines / ultrasonography
Electroencephalography
Image Enhancement
Mice
Mice, Transgenic
Recurrence
Somatosensory Cortex / ultrasonography
Grant Support
ID/Acronym/Agency:
F31 NS064753-01A2/NS/NINDS NIH HHS; NS057113/NS/NINDS NIH HHS; NS064753/NS/NINDS NIH HHS; R01 NS057113/NS/NINDS NIH HHS; R01 NS057113-04/NS/NINDS NIH HHS
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