Local Injection of Endothelin-1 in the Early Neonatal Rat Brain Models Ischemic Damage Associated with Motor Impairment and Diffuse Loss in Brain Volume. (21st November 2018)

• Record Type: Journal Article
• Authors: Wright, Jordan L.; Chu, Hannah X.; Kagan, Brett J.; Ermine, Charlotte M.; Kauhausen, Jessica A.; Parish, Clare L.; Sobey, Christopher G.; Thompson, Lachlan H.
• Is Part Of: Neuroscience. Volume 393(2018)
• Page Start: 110
• Page End: 122
• Publication Date: 2018-11-21
• Subjects: CP cerebral palsy -- ET-1 endothelin-1 -- HIE hypoxic ischemia encephalopathy -- MCA middle cerebral artery -- PVL periventricular leukomalacia -- PVWMI periventricular white matter injury; endothelin-1 -- cerebral palsy -- neonatal stroke -- white matter injury; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2018.09.043
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Focal injection of ET-1 into the newborn brain results in robust ischemic damage. Early analysis in this model revealed robust apoptosis and immune cell activation. Analysis of adult rats revealed permanent cortical and white matter atrophy. Adult rats exhibited gross motor deficits resulting from ET-1 ischemia at birth. ET-1 delivery to newborns is a simple, effective model for early neonatal ischemia. Abstract: Cerebral palsy is an irreversible movement disorder resulting from cerebral damage sustained during prenatal or neonatal brain development. As survival outcomes for preterm injury improve, there is increasing need to model ischemic injury at earlier neonatal time-points to better understand the subsequent pathological consequences. Here we demonstrate a novel neonatal ischemic model using focal administration of the potent vasoconstrictor peptide, endothelin-1 (ET-1), in newborn rats. The functional and histopathological outcomes compare favourably to those reported following the widely used hypoxic ischemia (HI) model. These include a robust motor deficit sustained into adulthood and recapitulation of hallmark features of preterm human brain injury, including atrophy of subcortical white matter and periventricular fiber bundles. Compared to procedures involving carotid artery manipulation and periods of hypoxia, the ET-1 ischemia model represents a rapid and technically simplified model more amenable to larger cohorts and with the potential to direct the locus of ischemic damage to specific brain areas.