Persistently Altered Metabolic Phenotype following Perinatal Excitotoxic Brain Injury

Benjamin J. Blaise, Leslie Schwendimann, Vibol Chhor, Vincent Degos, Mark P. Hodson, Guido Dallmann, Matthias Keller, Pierre Gressens, Bobbi Fleiss

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)
373 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)182-191
Number of pages10
JournalDevelopmental Neuroscience
Volume39
Early online date12 May 2017
DOIs
Publication statusPublished - Jul 2017

Keywords

  • Journal Article

Fingerprint

Dive into the research topics of 'Persistently Altered Metabolic Phenotype following Perinatal Excitotoxic Brain Injury'. Together they form a unique fingerprint.

Cite this