title: Unbiased Stereological Analysis of Reactive Astrogliosis to Estimate Age-Associated Cerebral White Matter Injury.
abstract: Cerebral white matter injury (WMI) contributes to cognitive dysfunction associated with pathological aging. Because reactive astrocyte-related factors contribute to remyelination failure after WMI, we sought accurate, cost-effective, and reproducible histopathological approaches for quantification of morphometric features of reactive astrogliosis in aged human white matter in patients with vascular brain injury (VBI). We compared 7 distinct approaches to quantify the features of glial fibrillary acidic protein (GFAP)-labeled astrocytes in the prefrontal white matter of brains from patients with VBI (n = 17, mean age 88.8 years) and controls that did not exhibit VBI (n = 11, mean age 86.6 years). Only modern stereological techniques (ie, optical fractionator and spaceballs) and virtual process thickness measurements demonstrated significant changes in astrocyte number, process length, or proximal process thickness in cases with VBI relative to controls. The widely employed methods of neuropathological scoring, antibody capture assay (histelide), area fraction fractionator, and Cavalieri point counting failed to detect significant differences in GFAP expression between the groups. Unbiased stereological approaches and virtual thickness measurements provided the only sensitive and accurate means to quantify astrocyte reactivity as a surrogate marker of WMI in human brains with VBI.
authors.affiliation: From the Department of Pediatrics, Oregon Health & Science University, Portland, Oregon (DWM, DDB, XG, SAB); Department of Neurology, Oregon Health & Science University, Portland, Oregon (SAB); and Department of Pathology, University of Washington, Seattle, Washington, District of Columbia (NOP, TJM, CDK). backs@ohsu.edu.
authors.forename: David W
authors.initials: DW
authors.lastname: McNeal
authors.affiliation: From the Department of Pediatrics, Oregon Health & Science University, Portland, Oregon (DWM, DDB, XG, SAB); Department of Neurology, Oregon Health & Science University, Portland, Oregon (SAB); and Department of Pathology, University of Washington, Seattle, Washington, District of Columbia (NOP, TJM, CDK).
authors.forename: Dieter D
authors.initials: DD
authors.lastname: Brandner
authors.affiliation: From the Department of Pediatrics, Oregon Health & Science University, Portland, Oregon (DWM, DDB, XG, SAB); Department of Neurology, Oregon Health & Science University, Portland, Oregon (SAB); and Department of Pathology, University of Washington, Seattle, Washington, District of Columbia (NOP, TJM, CDK).
authors.forename: Xi
authors.initials: X
authors.lastname: Gong
authors.affiliation: From the Department of Pediatrics, Oregon Health & Science University, Portland, Oregon (DWM, DDB, XG, SAB); Department of Neurology, Oregon Health & Science University, Portland, Oregon (SAB); and Department of Pathology, University of Washington, Seattle, Washington, District of Columbia (NOP, TJM, CDK).
authors.forename: Nadia O
authors.initials: NO
authors.lastname: Postupna
authors.affiliation: From the Department of Pediatrics, Oregon Health & Science University, Portland, Oregon (DWM, DDB, XG, SAB); Department of Neurology, Oregon Health & Science University, Portland, Oregon (SAB); and Department of Pathology, University of Washington, Seattle, Washington, District of Columbia (NOP, TJM, CDK).
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
authors.affiliation: From the Department of Pediatrics, Oregon Health & Science University, Portland, Oregon (DWM, DDB, XG, SAB); Department of Neurology, Oregon Health & Science University, Portland, Oregon (SAB); and Department of Pathology, University of Washington, Seattle, Washington, District of Columbia (NOP, TJM, CDK).
authors.forename: C Dirk
authors.initials: CD
authors.lastname: Keene
authors.affiliation: From the Department of Pediatrics, Oregon Health & Science University, Portland, Oregon (DWM, DDB, XG, SAB); Department of Neurology, Oregon Health & Science University, Portland, Oregon (SAB); and Department of Pathology, University of Washington, Seattle, Washington, District of Columbia (NOP, TJM, CDK).
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Back
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D020214:Cerebrovascular Trauma / Q000378:metabolism / Q000473:pathology*; D003430:Cross-Sectional Studies; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis*; D005911:Gliosis / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D056784:Leukoencephalopathies / Q000378:metabolism / Q000473:pathology*; D008297:Male; D011159:Population Surveillance; D013238:Stereotaxic Techniques; D066127:White Matter / Q000378:metabolism / Q000473:pathology
chemical_list: D005904:Glial Fibrillary Acidic Protein
keywords: Dementia; Glial fibrillary acidic protein; Reactive astrogliosis; Stereology; Vascular brain injury; White matter injury.