title: Subfield-specific neurovascular remodeling in the entorhino-hippocampal-organotypic slice culture as a response to oxygen-glucose deprivation and excitotoxic cell death.
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.
authors.affiliation: Department of Biomedicine, Section of Functional Neuroanatomy, University of Basel, Basel, Switzerland.
authors.forename: Sophorn
authors.initials: S
authors.lastname: Chip
authors.forename: Cordula
authors.initials: C
authors.lastname: Nitsch
authors.forename: Sven
authors.initials: S
authors.lastname: Wellmann
authors.forename: Josef P
authors.initials: JP
authors.lastname: Kapfhammer
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death; D062507:Claudin-5 / Q000096:biosynthesis; D018728:Entorhinal Cortex / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D042282:Microdissection; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010100:Oxygen / Q000378:metabolism*; D046509:Tissue Culture Techniques; D015854:Up-Regulation
chemical_list: D062507:Claudin-5; C491511:Cldn5 protein, mouse; D005947:Glucose; D010100:Oxygen