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Angiogenesis dysregulation in term asphyxiated newborns treated with hypothermia.

Shaikh H, Boudes E, Khoja Z, Shevell M, Wintermark P - PLoS ONE (2015)

Bottom Line: Neonatal encephalopathy following birth asphyxia is a major predictor of long-term neurological impairment.Angiogenesis is a demonstrated therapeutic target in adult stroke.We used Rules-Based Medicine multi-analyte profiling and protein array technologies to study the plasma concentration of 49 angiogenesis-related proteins.

View Article: PubMed Central - PubMed

Affiliation: Division of Newborn Medicine, Department of Pediatrics, McGill University, Montreal, Quebec, Canada.

ABSTRACT

Background: Neonatal encephalopathy following birth asphyxia is a major predictor of long-term neurological impairment. Therapeutic hypothermia is currently the standard of care to prevent brain injury in asphyxiated newborns but is not protective in all cases. More robust and versatile treatment options are needed. Angiogenesis is a demonstrated therapeutic target in adult stroke. However, no systematic study examines the expression of angiogenesis-related markers following birth asphyxia in human newborns.

Objective: This study aimed to evaluate the expression of angiogenesis-related protein markers in asphyxiated newborns developing and not developing brain injury compared to healthy control newborns.

Design/methods: Twelve asphyxiated newborns treated with hypothermia were prospectively enrolled; six developed eventual brain injury and six did not. Four healthy control newborns were also included. We used Rules-Based Medicine multi-analyte profiling and protein array technologies to study the plasma concentration of 49 angiogenesis-related proteins. Mean protein concentrations were compared between each group of newborns.

Results: Compared to healthy newborns, asphyxiated newborns not developing brain injury showed up-regulation of pro-angiogenic proteins, including fatty acid binding protein-4, glucose-6-phosphate isomerase, neuropilin-1, and receptor tyrosine-protein kinase erbB-3; this up-regulation was not evident in asphyxiated newborns eventually developing brain injury. Also, asphyxiated newborns developing brain injury showed a decreased expression of anti-angiogenic proteins, including insulin-growth factor binding proteins -1, -4, and -6, compared to healthy newborns.

Conclusions: These findings suggest that angiogenesis pathways are dysregulated following birth asphyxia and are putatively involved in brain injury pathology and recovery.

No MeSH data available.


Related in: MedlinePlus

Expression of angiogenesis-related protein markers at 24 hours of life.Mean concentrations in each group were compared. p values were calculated to highlight significant protein expression differences between the groups (* p < 0.05). For graphical representation, ratios between group mean concentrations were calculated and log transformed to obtain fold change data for each marker. (A) Fold changes in protein expression between asphyxiated newborns treated with hypothermia and healthy newborns. (B) Fold changes in protein expression between asphyxiated newborns developing and not developing brain injury.
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pone.0128028.g002: Expression of angiogenesis-related protein markers at 24 hours of life.Mean concentrations in each group were compared. p values were calculated to highlight significant protein expression differences between the groups (* p < 0.05). For graphical representation, ratios between group mean concentrations were calculated and log transformed to obtain fold change data for each marker. (A) Fold changes in protein expression between asphyxiated newborns treated with hypothermia and healthy newborns. (B) Fold changes in protein expression between asphyxiated newborns developing and not developing brain injury.

Mentions: Mean protein concentration values were compared between asphyxiated newborns developing and not developing brain injury and healthy newborns at 24 hours of life (“Fig 2”).


Angiogenesis dysregulation in term asphyxiated newborns treated with hypothermia.

Shaikh H, Boudes E, Khoja Z, Shevell M, Wintermark P - PLoS ONE (2015)

Expression of angiogenesis-related protein markers at 24 hours of life.Mean concentrations in each group were compared. p values were calculated to highlight significant protein expression differences between the groups (* p < 0.05). For graphical representation, ratios between group mean concentrations were calculated and log transformed to obtain fold change data for each marker. (A) Fold changes in protein expression between asphyxiated newborns treated with hypothermia and healthy newborns. (B) Fold changes in protein expression between asphyxiated newborns developing and not developing brain injury.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4440713&req=5

pone.0128028.g002: Expression of angiogenesis-related protein markers at 24 hours of life.Mean concentrations in each group were compared. p values were calculated to highlight significant protein expression differences between the groups (* p < 0.05). For graphical representation, ratios between group mean concentrations were calculated and log transformed to obtain fold change data for each marker. (A) Fold changes in protein expression between asphyxiated newborns treated with hypothermia and healthy newborns. (B) Fold changes in protein expression between asphyxiated newborns developing and not developing brain injury.
Mentions: Mean protein concentration values were compared between asphyxiated newborns developing and not developing brain injury and healthy newborns at 24 hours of life (“Fig 2”).

Bottom Line: Neonatal encephalopathy following birth asphyxia is a major predictor of long-term neurological impairment.Angiogenesis is a demonstrated therapeutic target in adult stroke.We used Rules-Based Medicine multi-analyte profiling and protein array technologies to study the plasma concentration of 49 angiogenesis-related proteins.

View Article: PubMed Central - PubMed

Affiliation: Division of Newborn Medicine, Department of Pediatrics, McGill University, Montreal, Quebec, Canada.

ABSTRACT

Background: Neonatal encephalopathy following birth asphyxia is a major predictor of long-term neurological impairment. Therapeutic hypothermia is currently the standard of care to prevent brain injury in asphyxiated newborns but is not protective in all cases. More robust and versatile treatment options are needed. Angiogenesis is a demonstrated therapeutic target in adult stroke. However, no systematic study examines the expression of angiogenesis-related markers following birth asphyxia in human newborns.

Objective: This study aimed to evaluate the expression of angiogenesis-related protein markers in asphyxiated newborns developing and not developing brain injury compared to healthy control newborns.

Design/methods: Twelve asphyxiated newborns treated with hypothermia were prospectively enrolled; six developed eventual brain injury and six did not. Four healthy control newborns were also included. We used Rules-Based Medicine multi-analyte profiling and protein array technologies to study the plasma concentration of 49 angiogenesis-related proteins. Mean protein concentrations were compared between each group of newborns.

Results: Compared to healthy newborns, asphyxiated newborns not developing brain injury showed up-regulation of pro-angiogenic proteins, including fatty acid binding protein-4, glucose-6-phosphate isomerase, neuropilin-1, and receptor tyrosine-protein kinase erbB-3; this up-regulation was not evident in asphyxiated newborns eventually developing brain injury. Also, asphyxiated newborns developing brain injury showed a decreased expression of anti-angiogenic proteins, including insulin-growth factor binding proteins -1, -4, and -6, compared to healthy newborns.

Conclusions: These findings suggest that angiogenesis pathways are dysregulated following birth asphyxia and are putatively involved in brain injury pathology and recovery.

No MeSH data available.


Related in: MedlinePlus