10.6084/m9.figshare.4986194.v1
McAdams R.M.
McAdams
R.M.
Fleiss B.
Fleiss
B.
Traudt C.
Traudt
C.
Schwendimann L.
Schwendimann
L.
Snyder J.M.
Snyder
J.M.
Haynes R.L.
Haynes
R.L.
Natarajan N.
Natarajan
N.
Gressens P.
Gressens
P.
Juul S.E.
Juul
S.E.
Supplementary Material for: Long-Term Neuropathological Changes Associated with Cerebral Palsy in a Nonhuman Primate Model of Hypoxic-Ischemic Encephalopathy
Karger Publishers
2017
Brain injury
Central nervous system
Cerebellum
Developing brain
Erythropoietin
Hypothermia therapy
Hypoxic-ischemic encephalopathy
Immunohistochemistry
Monkey
2017-05-09 08:46:13
Dataset
https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Long-Term_Neuropathological_Changes_Associated_with_Cerebral_Palsy_in_a_Nonhuman_Primate_Model_of_Hypoxic-Ischemic_Encephalopathy/4986194
<p><b><i>Background:</i></b> 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. <b><i>Methodology:</i></b> Thirty-four term <i>Macaca nemestrina</i>
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 (<i>n</i> = 11), therapeutic hypothermia (TH; <i>n</i> = 6), or TH + erythropoietin (Epo; <i>n</i>
= 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. <b><i>Results:</i></b> 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 in CP animals compared to that in control animals without
CP. <b><i>Conclusions/Significance:</i></b> In this nonhuman primate HIE
model, animals treated with TH + Epo had less brain pathology noted on
TBSS and IHC staining, which supports the long-term safety of TH + Epo
in the setting of HIE. Animals that developed CP showed white-matter
changes noted on TBSS, subtle histopathological changes in both the
white and gray matter, and brainstem injury that correlated with CP
severity. This HIE model may lend itself to further study of the
relationship between brainstem injury and CP.</p>