Vulnerability of the developing brain to hypoxic-ischemic damage: contribution of the cerebral vasculature to injury and repair?

Abstract

As clinicians attempt to understand the underlying reasons for the vulnerability of different regions of the developing brain to injury, it is apparent that little is known as to how hypoxia-ischemia may affect the cerebrovasculature in the developing infant. Most of the research investigating the pathogenesis of perinatal brain injury following hypoxia-ischemia has focused on excitotoxicity, oxidative stress and an inflammatory response, with the response of the developing cerebrovasculature receiving less attention. This is surprising as the presentation of devastating and permanent injury such as germinal matrix-intraventricular haemorrhage (GM-IVH) and perinatal stroke are of vascular origin, and the origin of periventricular leukomalacia (PVL) may also arise from poor perfusion of the white matter. This highlights that cerebrovasculature injury following hypoxia could primarily be responsible for the injury seen in the brain of many infants diagnosed with hypoxic-ischemic encephalopathy (HIE). Interestingly the highly dynamic nature of the cerebral blood vessels in the fetus, and the fluctuations of cerebral blood flow and metabolic demand that occur following hypoxia suggest that the response of blood vessels could explain both regional protection and vulnerability in the developing brain. However, research into how blood vessels respond following hypoxia-ischemia have mostly been conducted in adult models of ischemia or stroke, further highlighting the need to investigate how the developing cerebrovasculature responds and the possible contribution to perinatal brain injury following hypoxia. This review discusses the current concepts on the pathogenesis of perinatal brain injury, the development of the fetal cerebrovasculature and the blood brain barrier (BBB), and key mediators involved with the response of cerebral blood vessels to hypoxia.

Optimizing the Dose of Erythropoietin Required to Prevent Acute Ventilation-Induced Cerebral White Matter Injury in Preterm Lambs

“…Therefore, we examined the integrity of the BBB after ventilation and early EPO treatment to more accurately assess the impact of EPO on hemodynamics. Compromised cerebral vasculature resulting in increased BBB permeability and protein extravasation is a known contributor of preterm brain injury and VIBI [46] . A damaged BBB renders the preterm brain vulnerable to hemorrhage as well as infiltration of potentially toxic mediators; entry of systemic inflammatory cytokines and leukocytes into the brain can promote a localized cerebral inflammatory response [47] .…”

Neurodevelopmental Outcomes After Neonatal Surgery for Major Noncardiac Anomalies

“…Theoretically, comparable to the cardiac group, patients with NCCA are also at risk for developing perioperative brain damage. 14,52 Inflammation is among the known risk factors for developing brain injury. 53,54 Patients with NCCA can be more susceptible to neuronal damage, and preoperative inflammation in patients with gastroschisis can be considerable.…”

Effect of oxygen inhalation on cerebral blood flow velocity in premature neonates

“…In the present study, a GA of 32 wk was taken as the cutoff for subgroup analysis as blood vessels within the germinal matrix remain fragile till 32 wk of gestation (3,4). Cranial ultrasonographic examination was performed frequently, to detect GMH-IVH at the earliest.…”

“…Before 32 wk of gestation, the blood vessels within the subependymal germinal matrix are fragile. Active corticogenesis during this period, which demands an increased cerebral blood flow (CBF) to meet the higher oxygen and nutrient demands of the developing brain (3,4), makes these fragile vessels more prone to hemorrhage.…”