10.6084/m9.figshare.4996220.v1
Blaise B.J.
Blaise
B.J.
Schwendimann L.
Schwendimann
L.
Chhor V.
Chhor
V.
Degos V.
Degos
V.
Hodson M.P.
Hodson
M.P.
Dallmann G.
Dallmann
G.
Keller M.
Keller
M.
Gressens P.
Gressens
P.
Fleiss B.
Fleiss
B.
Supplementary Material for: Persistently Altered Metabolic Phenotype following Perinatal Excitotoxic Brain Injury
Karger Publishers
2017
Ibotenate
Stroke
Hypoxic-ischemic encephalopathy
Diffuse white matter injury
Metabolomics
Mass spectrometry
Metabonomics
Neonatal encephalopathy
2017-05-11 12:55:21
Dataset
https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Persistently_Altered_Metabolic_Phenotype_following_Perinatal_Excitotoxic_Brain_Injury/4996220
<p>Excitotoxicity plays a key role during insults to the developing
brain such as neonatal encephalopathy, stroke, and encephalopathy of
prematurity. Such insults affect many thousands of infants each year.
Excitotoxicity causes frank lesions due to cell death and gliosis and
disturbs normal developmental process, leading to deficits in learning,
memory, and social integration that persist into adulthood.
Understanding the underlying processes of the acute effects of
excitotoxicity and its persistence during brain maturation provides an
opportunity to identify mechanistic or diagnostic biomarkers, thus
enabling and designing possible therapies. We applied mass spectrometry
to provide metabolic profiles of brain tissue and plasma over time
following an excitotoxic lesion (intracerebral ibotenate) to the
neonatal (postnatal day 5) mouse brain. We found no differences between
the plasma from the control (PBS-injected) and excitotoxic
(ibotenate-injected) groups over time (on postnatal days 8, 9, 10, and
30). In the brain, we found that variations in amino acids (arginine,
glutamine, phenylananine, and proline) and glycerophospholipids were
sustaining acute and delayed (tertiary) responses to injury. In
particular, the effect of the excitotoxic lesion on the normal profile
of development was linked to alterations in a fingerprint of
glycerophospolipids and amino acids. Specifically, we identified
increases in the amino acids glutamine, proline, serine, threonine,
tryptophan, valine, and the sphingolipid SM C26:1, and decreases in the
glycerophospholipids, i.e., the arachidonic acid-containing
phosphatidylcholine (PC aa) C30:2 and the PC aa C32:3. This study
demonstrates that metabolic profiling is a useful approach to identify
acute and tertiary effects in an excitotoxic lesion model, and
generating a short list of targets with future potential in the hunt for
identification, stratification, and possibly therapy.</p>