title: Different dynamics of aquaporin 4 and glutamate transporter-1 distribution in the perineuronal and perivascular compartments during ischemic stroke.
abstract: Aquaporin-4 (AQP4) and glutamate transporter-1 (GLT-1) represent the major water and glutamate astrocyte buffering gateways in the brain. Utilizing perilesional ischemic human cortices, we have performed here for the first time an integrative assessment on both AQP4 and GLT-1, and on their proximity to blood vessels and neurons. Counting the relative number of AQP4±/GLT-1±/glial fibrillary acidic protein± cells showed that double-positive variants were overall most frequent, and their number tended to decrease from organized and recent perilesional cortices to controls. AQP4/GLT-1 colocalization showed higher coefficients for the perilesional cortices compared with controls, suggesting an increased water/glutamate-buffering capability. Distance frequency analysis of AQP4/GLT-1 in relationship to neurons showed that both markers were concentrated at 20-40 μm around the perikarya; with AQP4 being more abundant in close proximity, these differences were not being driven by changes in neuropil density alone. Our study suggests a dual, simultaneous astrocytic function depending on the relative distance to neurons and vessels, with increased water and glutamate-buffering capability in the mid perineuronal space, and an increased water-buffering capability in the immediate perineuronal space, even higher than around vessels. Thus, adding specific AQP4/GLT-1 modulator agents selectively depending on the acute/chronic phase of stroke might increase the efficacy of existing treatments.
authors.affiliation: Research Center for Microscopic Morphology and Immunology, Department of Morphology, University of Medicine and Pharmacy of Craiova, Craiova, Romania.
authors.forename: Laurentiu
authors.initials: L
authors.lastname: Mogoanta
authors.forename: Marius
authors.initials: M
authors.lastname: Ciurea
authors.forename: Ionica
authors.initials: I
authors.lastname: Pirici
authors.forename: Claudiu
authors.initials: C
authors.lastname: Margaritescu
authors.forename: Cristiana
authors.initials: C
authors.lastname: Simionescu
authors.forename: Daniela A
authors.initials: DA
authors.lastname: Ion
authors.forename: Daniel
authors.initials: D
authors.lastname: Pirici
mesh_terms: D000368:Aged; D027322:Amino Acid Transport System X-AG / Q000032:analysis* / Q000378:metabolism; D051401:Aquaporin 4 / Q000032:analysis* / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism; D020521:Stroke / Q000378:metabolism* / Q000473:pathology
chemical_list: C496030:AQP4 protein, human; D027322:Amino Acid Transport System X-AG; D051401:Aquaporin 4
keywords: aquaporin 4; astrocytes; blood vessels; glutamate transporter 1; ischemic stroke; neurons