Long-Term Neuropathological Changes Associated with Cerebral Palsy in a Nonhuman Primate Model of Hypoxic-Ischemic Encephalopathy

McAdams, R, Fleiss, B, Traudt, C, Schwendimann, L, Snyder, J, Haynes, R, Natarajan, N, Gressens, P and Juul, S 2017, 'Long-Term Neuropathological Changes Associated with Cerebral Palsy in a Nonhuman Primate Model of Hypoxic-Ischemic Encephalopathy', Developmental Neuroscience, vol. 39, no. 14, pp. 124-140.


Document type: Journal Article
Collection: Journal Articles

Title Long-Term Neuropathological Changes Associated with Cerebral Palsy in a Nonhuman Primate Model of Hypoxic-Ischemic Encephalopathy
Author(s) McAdams, R
Fleiss, B
Traudt, C
Schwendimann, L
Snyder, J
Haynes, R
Natarajan, N
Gressens, P
Juul, S
Year 2017
Journal name Developmental Neuroscience
Volume number 39
Issue number 14
Start page 124
End page 140
Total pages 17
Publisher S. Karger AG
Abstract Background: Cerebral palsy (CP) is the most common motor disability in childhood, with a worldwide prevalence of 1.5-4/1,000 live births. Hypoxic-ischemic encephalopathy (HIE) contributes to the burden of CP, but the long-term neuropathological findings of this association remain limited. Methodology: Thirty-four term Macaca nemestrina macaques were included in this long-term neuropathological study: 9 control animals delivered by cesarean section and 25 animals with perinatal asphyxia delivered by cesarean section after 15-18 min of umbilical cord occlusion (UCO). UCO animals were randomized to saline (n = 11), therapeutic hypothermia (TH; n = 6), or TH + erythropoietin (Epo; n = 8). Epo was given on days 1, 2, 3, and 7. Animals had serial developmental assessments and underwent magnetic resonance imaging with diffusion tensor imaging at 9 months of age followed by necropsy. Histology and immunohistochemical (IHC) staining of brain and brainstem sections were performed. Results: All UCO animals demonstrated and met the standard diagnostic criteria for human neonates with moderate-to-severe HIE. Four animals developed moderate-to-severe CP (3 UCO and 1 UCO + TH), 9 had mild CP (2 UCO, 3 UCO + TH, 3 UCO + TH + Epo, and 1 control), and 2 UCO animals died. None of the animals treated with TH + Epo died, had moderate-to-severe CP, or demonstrated signs of long-term neuropathological toxicity. Compared to animals grouped together as having no CP (no-CP; controls and mild CP only), animals with CP (moderate and severe) demonstrated decreased fractional anisotropy of multiple white-matter tracts including the corpus callosum and internal capsule, when using Tract-Based Spatial Statistics (TBSS). Animals with CP had decreased staining for cortical neurons and increased brainstem glial scarring compared to animals without CP. The cerebellar cell density of the internal granular layer and white matter was decreased i
Subject Neurology and Neuromuscular Diseases
Paediatrics
Keyword(s) Brain injury
Central nervous system
Cerebellum
Developing brain
Erythropoietin
Hypothermia therapy
Hypoxic-ischemic encephalopathy
Immunohistochemistry
Monkey
DOI - identifier 10.1159/000470903
Copyright notice © 2017 S. Karger AG, Basel. Copyright: All rights reserved.
ISSN 0378-5866
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