Unbiased stereological analysis of reactive astrogliosis to estimate age-associated cerebral white matter injury

David W. McNeal, Dieter D. Brandner, Xi Gong, Nadia O. Postupna, Thomas J. Montine, C. Dirk Keene, Stephen Back

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Cerebral white matter injury (WMI) contributes to cognitive dysfunction associated with pathological aging. Because reactive astrocyterelated 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.

Original languageEnglish (US)
Pages (from-to)539-554
Number of pages16
JournalJournal of Neuropathology and Experimental Neurology
Volume75
Issue number6
DOIs
StatePublished - Jun 1 2016

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Cerebrovascular Trauma
Astrocytes
Wounds and Injuries
Glial Fibrillary Acidic Protein
Brain
Research Design
Biomarkers
White Matter
Costs and Cost Analysis
Antibodies

Keywords

  • Dementia
  • Glial fibrillary acidic protein
  • Reactive astrogliosis
  • Stereology
  • Vascular brain injury
  • White matter injury

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Unbiased stereological analysis of reactive astrogliosis to estimate age-associated cerebral white matter injury. / McNeal, David W.; Brandner, Dieter D.; Gong, Xi; Postupna, Nadia O.; Montine, Thomas J.; Dirk Keene, C.; Back, Stephen.

In: Journal of Neuropathology and Experimental Neurology, Vol. 75, No. 6, 01.06.2016, p. 539-554.

Research output: Contribution to journalArticle

McNeal, David W. ; Brandner, Dieter D. ; Gong, Xi ; Postupna, Nadia O. ; Montine, Thomas J. ; Dirk Keene, C. ; Back, Stephen. / Unbiased stereological analysis of reactive astrogliosis to estimate age-associated cerebral white matter injury. In: Journal of Neuropathology and Experimental Neurology. 2016 ; Vol. 75, No. 6. pp. 539-554.
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