Persistently altered metabolic phenotype following perinatal excitotoxic brain injury

Blaise, Benjamin J. , Schwendimann, Leslie, Chhor, Vibol , Degos, Vincent, Hodson, Mark P., Dallmann, Guido, Keller, Matthias, Gressens, Pierre and Fleiss, Bobbi  (2017) Persistently altered metabolic phenotype following perinatal excitotoxic brain injury. Developmental Neuroscience, 39 1-4: 182-191. doi:10.1159/000464131


Author Blaise, Benjamin J. 
Schwendimann, Leslie
Chhor, Vibol 
Degos, Vincent
Hodson, Mark P.
Dallmann, Guido
Keller, Matthias
Gressens, Pierre
Fleiss, Bobbi 
Title Persistently altered metabolic phenotype following perinatal excitotoxic brain injury
Journal name Developmental Neuroscience   Check publisher's open access policy
ISSN 1421-9859
0378-5866
Publication date 2017-07-01
Sub-type Article (original research)
DOI 10.1159/000464131
Open Access Status Not yet assessed
Volume 39
Issue 1-4
Start page 182
End page 191
Total pages 10
Place of publication Basel, Switzerland
Publisher S. Karger AG
Language eng
Abstract 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.
Keyword Diffuse white matter injury
Hypoxic-ischemic encephalopathy
Ibotenate
Mass spectrometry
Metabolomics
Metabonomics
Neonatal encephalopathy
Stroke
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Pharmacy Publications
Australian Institute for Bioengineering and Nanotechnology Publications
 
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