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Published on: October 25, 2016
Morphological changes in white matter astrocytes in response to hypoxia/ischemia in the neonatal pig
Susan M Sullivan1, S Tracey Björkman, Stephanie M Miller
1Centre for Clinical Research and Perinatal Research Centre, The University of Queensland, Herston, Brisbane, QLD, 4029, Australia. susan.sullivan@uq.edu.au
Insights
Perinatal hypoxic-ischemic (H/I) insults significantly damage white matter in premature infants. This study reveals H/I injury alters white matter astrocyte morphology and reduces GFAP expression, suggesting astrocytes as a therapeutic target.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Neonatal Research
Background:
- White matter damage is a critical issue in preterm infants, often linked to hypoxic-ischemic (H/I) insults.
- Astrocytes are crucial for white matter integrity, regulating extracellular glutamate and protecting oligodendrocytes and axons.
- Previous research indicated grey matter astrocyte changes post-H/I insult.
Purpose of the Study:
- To investigate the morphological and quantitative changes in white matter astrocytes following perinatal H/I insult.
- To assess the role of astrocytes in the pathology of white matter damage in neonatal brains.
Main Methods:
- Utilized GFAP immunohistochemistry and Golgi-Kopsch staining in neonatal pig brains.
- Compared control brains with those exposed to a perinatal H/I insult.
- Employed image analysis to quantify astrocyte morphology and GFAP-immunoreactive areas.
Main Results:
- A significant 46% decrease in GFAP-immunoreactive area in the subcortical white matter of H/I-insulted brains.
- Observed alterations in white matter astrocyte morphology post-H/I insult.
- Demonstrated a reduction in the average size of white matter astrocytes from 649µm² to 426µm².
Conclusions:
- Perinatal H/I insults induce significant changes in white matter astrocytes, including reduced GFAP expression and altered morphology.
- These astrocyte alterations suggest their contribution to white matter damage pathology.
- Astrocytes represent a potential novel therapeutic target for improving outcomes after H/I insults in neonates.
Abstract:
White matter damage is a significant problem in the human pre-term baby. Damage to white matter is usually associated with injury or insults to babies born prematurely, typically before 32weeks' gestation, however there is increasing evidence of both grey and white matter damage occurring after 32weeks' gestation. Astrocytes play a vital role in white matter, regulating molecules such as glutamate in the extracellular space and preventing excitotoxic damage to neighbouring oligodendrocytes and axons. We have previously described dramatic changes in grey matter astrocytes in response to a hypoxic/ischemic (H/I) insult around the time of birth. In this study, we have used GFAP immunohistochemistry and Golgi-Kopsch staining to examine the morphology of white matter astrocytes in control neonatal pig brains, and in the brains of animals exposed to the same (perinatal) H/I insult. We demonstrate that the areal percentage of the section occupied by GFAP-immunoreactive processes and cell bodies is significantly decreased (by 46%, P<0.0001) in subcortical white matter from H/I brains. This loss of GFAP was accompanied by alterations in astrocyte morphology and an overall decrease in the size (field of section occupied by an individual astrocyte) of white matter astrocytes from 649microm(2) to 426microm(2), as revealed by Golgi-Kopsch staining and image analysis. These data suggest that astrocytes may contribute to the pathology of white matter damage following an H/I insult around the time of birth, and suggest that astrocytes may offer a novel target for therapies to improve outcomes after H/I.
