Proteomic profiles in cerebrospinal fluid predicted death and disability in term infants with perinatal asphyxia : A pilot study

• Aim: Perinatal asphyxia, resulting in hypoxic-ischaemic encephalopathy (HIE), has been associated with high mortality rates and severe lifelong neurodevelopmental disabilities. Our aim was to study the association between the proteomic profile in cerebrospinal fluid (CSF) and the degree of HIE and long-term outcomes. Methods: We prospectively enrolled 18-term born infants with HIE and 10-term born controls between 2000 and 2004 from the Karolinska University Hospital. An antibody suspension bead array and FlexMap3D analysis was used to characterise 178 unique brain-derived and inflammation associated proteins in their CSF. Results: Increased CSF concentrations of several brain-specific proteins were observed in the proteome of HIE patients compared with the controls. An upregulation of neuroinflammatory pathways was also noted and this was confirmed by pathway analysis. Principal component analysis revealed a gradient from favourable to unfavourable HIE grades and outcomes. The proteins that provided strong predictors were structural proteins, including myelin basic protein and alpha-II spectrin. The functional proteins included energy-related proteins like neuron-specific enolase and synaptic regulatory proteins. Increased CSF levels of 51 proteins correlated with adverse outcomes in infants with HIE. Conclusion: Brain-specific proteins and neuroinflammatory mediators in CSF may predict HIE degrees and outcomes after perinatal asphyxia. 

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Pediatrik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Pediatrics (hsv//eng)

Nyckelord

biomarkers

cerebrospinal fluid

hypoxic-ischaemic encephalopathy

perinatal asphyxia

protein profile

alpha2 spectrin

brain protein

myelin basic protein

neuron specific enolase

proteome

regulator protein

spectrin

structural protein

synaptic regulatory protein

unclassified drug

adverse outcome

Article

child death

clinical article

clinical outcome

controlled study

disability

female

human

hypoxic ischemic encephalopathy

infant

male

pathway analysis

pilot study

principal component analysis

prospective study

protein cerebrospinal fluid level

protein fingerprinting

protein microarray

upregulation

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)