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Metabolomic Profiling of Cerebral Palsy Brain Tissue Reveals Novel Central Biomarkers and Biochemical Pathways Associated with the Disease: A Pilot Study

1
Department of Obstetrics and Gynecology, Maternal Fetal Medicine Division, Beaumont Health System, 3811 W. 13 Mile Road, Royal Oak, MI 48073, USA
2
Oakland University-William Beaumont School of Medicine, Beaumont Health, 3811 W. 13 Mile Road, Royal Oak, MI 48073, USA
3
Beaumont Research Institute, Beaumont Health, 3811 W. 13 Mile Road, Royal Oak, MI 48073, USA
4
Departments of Mathematics and Computer Sciences, Albion College, 611 E. Porter St., Albion, MI 49224, USA
*
Author to whom correspondence should be addressed.
Metabolites 2019, 9(2), 27; https://doi.org/10.3390/metabo9020027
Received: 9 January 2019 / Revised: 29 January 2019 / Accepted: 31 January 2019 / Published: 2 February 2019
(This article belongs to the Special Issue Metabolomics in Neurodegenerative Disease)
Cerebral palsy (CP) is one of the most common causes of motor disability in childhood, with complex and heterogeneous etiopathophysiology and clinical presentation. Understanding the metabolic processes associated with the disease may aid in the discovery of preventive measures and therapy. Tissue samples (caudate nucleus) were obtained from post-mortem CP cases (n = 9) and age- and gender-matched control subjects (n = 11). We employed a targeted metabolomics approach using both 1H NMR and direct injection liquid chromatography-tandem mass spectrometry (DI/LC-MS/MS). We accurately identified and quantified 55 metabolites using 1H NMR and 186 using DI/LC-MS/MS. Among the 222 detected metabolites, 27 showed significant concentration changes between CP cases and controls. Glycerophospholipids and urea were the most commonly selected metabolites used to develop predictive models capable of discriminating between CP and controls. Metabolomics enrichment analysis identified folate, propanoate, and androgen/estrogen metabolism as the top three significantly perturbed pathways. We report for the first time the metabolomic profiling of post-mortem brain tissue from patients who died from cerebral palsy. These findings could help to further investigate the complex etiopathophysiology of CP while identifying predictive, central biomarkers of CP. View Full-Text
Keywords: cerebral palsy; metabolomics; 1H NMR; targeted mass spectrometry; metabolic pathways cerebral palsy; metabolomics; 1H NMR; targeted mass spectrometry; metabolic pathways
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MDPI and ACS Style

Alpay Savasan, Z.; Yilmaz, A.; Ugur, Z.; Aydas, B.; Bahado-Singh, R.O.; Graham, S.F. Metabolomic Profiling of Cerebral Palsy Brain Tissue Reveals Novel Central Biomarkers and Biochemical Pathways Associated with the Disease: A Pilot Study. Metabolites 2019, 9, 27.

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