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Subfield-specific neurovascular remodeling in the entorhino-hippocampal-organotypic slice culture as a response to oxygen-glucose deprivation and excitotoxic cell death


Chip, Sophorn; Nitsch, Cordula; Wellmann, Sven; Kapfhammer, Josef P (2013). Subfield-specific neurovascular remodeling in the entorhino-hippocampal-organotypic slice culture as a response to oxygen-glucose deprivation and excitotoxic cell death. Journal of Cerebral Blood Flow and Metabolism, 33(4):508-518.

Abstract

Transient ischemia causes delayed neurodegeneration in selective brain areas, particularly in the CA1 field of the hippocampus. This is accompanied by neurovascular impairment. It is unknown whether neurodegeneration is the cause or consequence of vascular changes. In an entorhino-hippocampal-organotypic slice culture system with well-preserved blood vessels, we studied the interplay between neurodegeneration and neurovasculature. Short-term oxygen and glucose deprivation (OGD) resulted in upregulation of hypoxic markers and with a delay of 24 to 48 hours in selective nerve cell death in CA1. In parallel, local vessel density decreased as detected by markers of endothelial cells and of the extracellular matrix. Claudin-5, a tight junction protein and marker of the blood-brain barrier was reduced. Preventing neuronal death with tetrodotoxin or 6-cyano-7-nitroquinoxaline-2,3-dione rescued blood vessels, suggesting that vessel loss is not due to OGD per se but a consequence of neuronal death. Induction of excitotoxic neuronal death with AMPA caused widespread neurodegeneration, but vessel reduction was confined to CA1. In dentate gyrus without neuronal loss, vessel density increased. We propose that neuronal stress and death influence maintenance, loss and remodeling of the neurovasculature and that the type of vascular response is in addition determined by local factors within the hippocampus.Journal of Cerebral Blood Flow & Metabolism advance online publication, 12 December 2012; doi:10.1038/jcbfm.2012.190.

Abstract

Transient ischemia causes delayed neurodegeneration in selective brain areas, particularly in the CA1 field of the hippocampus. This is accompanied by neurovascular impairment. It is unknown whether neurodegeneration is the cause or consequence of vascular changes. In an entorhino-hippocampal-organotypic slice culture system with well-preserved blood vessels, we studied the interplay between neurodegeneration and neurovasculature. Short-term oxygen and glucose deprivation (OGD) resulted in upregulation of hypoxic markers and with a delay of 24 to 48 hours in selective nerve cell death in CA1. In parallel, local vessel density decreased as detected by markers of endothelial cells and of the extracellular matrix. Claudin-5, a tight junction protein and marker of the blood-brain barrier was reduced. Preventing neuronal death with tetrodotoxin or 6-cyano-7-nitroquinoxaline-2,3-dione rescued blood vessels, suggesting that vessel loss is not due to OGD per se but a consequence of neuronal death. Induction of excitotoxic neuronal death with AMPA caused widespread neurodegeneration, but vessel reduction was confined to CA1. In dentate gyrus without neuronal loss, vessel density increased. We propose that neuronal stress and death influence maintenance, loss and remodeling of the neurovasculature and that the type of vascular response is in addition determined by local factors within the hippocampus.Journal of Cerebral Blood Flow & Metabolism advance online publication, 12 December 2012; doi:10.1038/jcbfm.2012.190.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neonatology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2013
Deposited On:21 Feb 2013 09:45
Last Modified:05 Apr 2016 16:31
Publisher:Nature Publishing Group
ISSN:0271-678X
Publisher DOI:https://doi.org/10.1038/jcbfm.2012.190
PubMed ID:23232944

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