Regional metabolic status of the E–18 rat fetal brain following transient hypoxia/ischemia

Abstract

Increasing evidence indicates that fetal metabolic stress may result in a variety of post-natal perturbations during brain development. The goal of the study was to determine the duration of hypoxia/ischemia that would elicit a demonstrable regional depression of metabolism in the fetal brain and further to examine several end-points to determine if the metabolic stress affects the developing brain. The uterine artery and uterine branch of the ovarian artery were occluded with aneurysm clamps for a period of 45 min, the clips removed and the metabolites in five regions of the perinatal brain were measured at 0, 2 and 6 h of reflow. Regional P-creatine, ATP and glucose levels were significantly depleted at the end of the 45 min occlusion. The levels of glycogen and glutamate at the end of the occlusion indicated a decreasing trend which was not significant. The concentration of citrate remained essentially unchanged at the end of the occlusion. To ensure that the insult was not lethal to the tissue, the recovery of the metabolites was examined at 2 and 6 h of reflow and generally the concentrations of the high-energy phosphates and glucose were normal or near-normal by 6 h of reperfusion in the five regions of the brain examined. The changes in the metabolites indicate that 45 min of hypoxia/ischemia is an appropriate model for studying neonatal development after fetal metabolic stress.

Mild intrauterine hypoperfusion reproduces neurodevelopmental disorders observed in prematurity

“…In contrast, there are many models of total intrauterine ischemia that have been developed to study prenatal brain injury1920212223. As a result, brain injuries caused by the total reduction of intrauterine perfusion has been well delineated, whereas very little is known regarding the impact of MIUH.…”

Prenatal Hypoxic-Ischemic Insult Changes the Distribution and Number of NADPH-Diaphorase Cells in the Cerebellum

“…The HI insult could alter the normal development of the EGL by an increase in cell death, which could be associated with changes in the microenvironment, such as increases in inflammatory cytokines and free radical levels, as already shown in the cerebral cortex by Robinson and colleagues [40]. The higher levels of inflammatory cytokines as well as the increase in lactate levels in cerebellar neuroepithelia after HI insult [46] could lead to an increase in cellular death in the EGL, and the resulting inflammation could provoke the translocation and hyper-stimulation of NOS in the dendritic trees, distributing the enzyme to the place of higher activity.…”

“…The forceps were left in place clamping the arteries for 45 min, during which time the uterine horns were kept moist. A clamping period of 45 minutes was chosen because it is the minimum period of time that results in most of the morphological changes that were reported in previous papers [40], [46], [47]. After this period, the haemostatic forceps were removed, the uterine horns replaced in the abdominal cavity and the abdominal wound sutured in layers.…”

Establishment of a hypoxia ischemia reperfusion brain damage model in neonatal rats

“…Amara used the suture-occluded method to establish a unilateral, normoxic, focal transient middle cerebral artery occlusion (tMCAO) model using P10 rats [28] . Placental ischemia reperfusion model is established by occluding the uterine artery temporarily with an aneurysm clip to simulate hypoxia ischemia reperfusion that mimics the fetal intrauterine status [29] . Further, Michelle et al established a model of delayed cesarean after hysterectomy based on the placental ischemia reperfusion model [30] .…”