title: Brain-derived circulating endothelial cells in peripheral blood of newborn infants with seizures: a potential biomarker for cerebrovascular injury.
abstract: Neonatal seizures have been associated with cerebrovascular endothelial injury and neurological disabilities. In a piglet model, the long-term loss of endothelial regulation of cerebral blood flow coincides with the surge of brain-derived circulating endothelial cells (BCECs) in blood. We hypothesized that BCECs could serve as a noninvasive biomarker of cerebrovascular injury in neonates with seizures. In a prospective pilot feasibility study, we enrolled newborn infants with confirmed diagnoses of perinatal asphyxia and intraventricular hemorrhage (IVH); both are commonly associated with seizures. Infants without clinical evidence of cerebrovascular injuries were representative of the control group. BCECs were detected in the CD45-negative fraction of peripheral blood mononuclear cells by coexpression of CD31 (common endothelial antigen) and GLUT1 (blood-brain barrier antigen) via automated flow cytometry method. In Infants with asphyxia (n = 12) and those with IVH grade III/IV (n = 5), the BCEC levels were 9.9 ± 0.9% and 19.0 ± 2.0%, respectively. These levels were significantly higher than the control group (n = 27), 0.9 ± 0.2%, P < 0.001. BCECs in infants with cerebrovascular insults with documented clinical seizures (n = 10; 16.8 ± 1.3%) were significantly higher than infants with cerebrovascular insults with subclinical or no seizures (n = 7; 9.5 ± 1.2%); P < 0.001. BCEC levels decreased with seizure control. BCECs levels were elevated in infants with seizures caused by severe IVH and perinatal asphyxia. We suggest that monitoring BCEC levels in peripheral blood can potentially offer a biological marker that reflects cerebrovascular insult and recovery. Further studies with a larger number of patients are required to support these findings.
authors: Department of Pediatrics, The University of Tennessee Health Science Center (UTHSC), Memphis, Tennessee Department of Physiology, The University of Tennessee Health Science Center (UTHSC), Memphis, Tennessee Department of Neuroscience Institute, The University of Tennessee Health Science Center (UTHSC), Memphis, Tennessee Department of Obstetrics and Gynecology, The University of Tennessee Health Science Center (UTHSC), Memphis, Tennessee mpourcyrous@uthsc.edu.
authors: Massroor
authors: M
authors: Pourcyrous
authors: Department of Physiology, The University of Tennessee Health Science Center (UTHSC), Memphis, Tennessee.
authors: Shyamali
authors: S
authors: Basuroy
authors: Department of Physiology, The University of Tennessee Health Science Center (UTHSC), Memphis, Tennessee.
authors: Dilyara
authors: D
authors: Tcheranova
authors: Division of Biostatistics and Pediatrics, Department of Public Health Sciences, Miller School of Medicine University of Miami, Coral Gables, Florida.
authors: Kristopher L
authors: KL
authors: Arheart
authors: Department of Pediatrics, The University of Tennessee Health Science Center (UTHSC), Memphis, Tennessee.
authors: Mohamad T
authors: http://orcid.org/0000-0002-6513-2958
authors: MT
authors: Elabiad
authors: Department of Pediatrics, The University of Tennessee Health Science Center (UTHSC), Memphis, Tennessee Department of Physiology, The University of Tennessee Health Science Center (UTHSC), Memphis, Tennessee Department of Neuroscience Institute, The University of Tennessee Health Science Center (UTHSC), Memphis, Tennessee.
authors: Charles W
authors: CW
authors: Leffler
authors: Department of Physiology, The University of Tennessee Health Science Center (UTHSC), Memphis, Tennessee Department of Neuroscience Institute, The University of Tennessee Health Science Center (UTHSC), Memphis, Tennessee.
authors: Helena
authors: H
authors: Parfenova
keywords: Asphyxia; BCECs; CECs; HIE; IVH; neonates