title: Bone marrow-derived nonreactive astrocytes in the mouse brain after permanent middle cerebral artery occlusion.
abstract: We studied the effect of permanent unilateral middle cerebral artery occlusion (PMCAO) on the generation of bone marrow (BM)-derived astrocytes in female mice previously transplanted with enhanced green fluorescent protein-expressing BM from male donors. In addition to an untreated PMCAO group, one group of mice also received intracerebral infusion of transforming growth factor-alpha, resulting in a decrease in the size of the infarct. Two months after PMCAO, we found a specific type of astrocyte of BM origin in the side of the injury, near the lesion. These astrocytes did not express glial fibrillary acidic protein (GFAP) by conventional fluorescence immunostaining; however, GFAP was easily detectable by tyramide signal amplification. These cells also expressed S100β, confirming their astrocytic character. Unlike the endogenous reactive astrocytes, these BM-derived astrocytes did not proliferate during the first week of ischemia and did not contribute to the glial scar formation. Transforming growth factor-alpha infusion increased the number of BM-derived astrocytes, without affecting their distribution. Interestingly, exclusively by tyramide signal amplification staining, we found that endogenous astrocytes displaying an identical morphology were also present in control mouse and human brains. Our data demonstrate that a subpopulation of nonreactive astrocytes expressing low levels of GFAP can originate from transplanted BM in the ischemic brain. We believe that these cells represent a subpopulation of astrocytes earlier considered to be GFAP negative. The high number of astrocytes with identical morphology and chemical character in control brains suggest that these type of astrocytes may have important functional role in the central nervous system that calls for further studies.
authors.affiliation: National Institute of Dental and Craniofacial Research, National Institute of Health, Bethesda, Maryland 20892, USA.
authors.forename: Zsuzsanna E
authors.initials: ZE
authors.lastname: Tóth
authors.forename: Ronen R
authors.initials: RR
authors.lastname: Leker
authors.forename: Tal
authors.initials: T
authors.lastname: Shahar
authors.forename: Andras
authors.initials: A
authors.lastname: Bratincsak
authors.forename: Ildiko
authors.initials: I
authors.lastname: Szalayova
authors.forename: Sharon
authors.initials: S
authors.lastname: Key
authors.forename: Miklós
authors.initials: M
authors.lastname: Palkovits
authors.forename: Riccardo
authors.initials: R
authors.lastname: Cassiani-Ingoni
authors.forename: Eva
authors.initials: E
authors.lastname: Mezey
mesh_terms: D000328:Adult; D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D002545:Brain Ischemia / Q000473:pathology / Q000628:therapy; D002452:Cell Count; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D009414:Nerve Growth Factors / Q000378:metabolism; D012038:Regeneration; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000494:pharmacology
chemical_list: D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D016211:Transforming Growth Factor alpha