Over the past decade, much has been learned about the cellular and molecular mechanisms underlying hypoxic-ischemic (H-I) injury in the preterm human brain. The pathogenesis of H-I brain injury is now understood to be multifactorial and quite complex, depending on (i) the severity, intensity and timing of asphyxia, (ii) selective ischemic vulnerability, (iii) the degree of maturity of the brain, and (iv) the characteristics of the ensuing reoxygenation/reperfusion phase. Each of these factors has differential effects on the distinct cell populations in the brain, with certain specific cell types being particularly vulnerable in the developing brain. In this review, we discuss the role of the blood vessels and the distinct cell populations, which are the mayor constitutive elements of the immature brain, in the pathophysiology of H-I lesion. The presence of fragile and poorly anastomosed blood vessels and the existence of disturbances in the blood-brain barrier alter blood flow, vascular tone and nutrient delivery. Brain cells are sensitive to the overstimulation of neurotransmitter receptors, particularly glutamate receptors, which can provoke excitotoxicity leading to the death of neurons and other cells such as astrocytes and oligodendrocyte progenitors. Microglial activation by means of excitatory amino acids and by leukocyte migration initiates the inflammatory response giving rise to an increase in regional cerebral blood flow and promoting astrocyte and oligodendrocyte injuries. A better understanding of these aspects of H-I injury will contribute to more efficient strategies for the management of the associated damage.

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Our results suggest that regional cerebral blood flow and the presence of apoptotic cells, 3 h after hypoxic-ischemic injury, are correlated.

Aim: To evaluate the effect of cerebral hypoxia‐ischaemia induced by partial occlusion of the umbilical cord on the relationship of the regional cerebral blood flow and the cerebral cell death in near‐term fetal lambs. Methods: Fifteen near‐term lambs were assigned to two hypoxic‐ischaemic groups with or without life support (3 h), and a healthy one. Hypoxia‐ischaemia was induced by partial occlusion of the umbilical cord (60 min). Routine light and electron microscopy, and the TUNEL method for apoptosis were performed. Regional cerebral blood flow was measured by coloured microspheres. Cardiovascular, gas exchange and pH parameters were also evaluated. Results: Both hypoxic‐ischaemic groups produced a transient acidosis and a decrease of base excess in comparison to the healthy group. Cortical and cerebellar zones, where the regional cerebral blood flow values were similar to baseline, showed an increased number of oligodendrocyte‐like apoptotic cells. In contrast, in the inner zones, where regional cerebral blood flow was increased, the number of apoptotic cells did not increase. Necrotic neurons were observed in the basal nuclei, mesencephalon, pons and deep cerebellar nuclei. Conclusion: Our results suggest that regional cerebral blood flow and the presence of apoptotic cells, 3 h after hypoxic‐ischemic injury, are correlated.

BackgroundFentanyl is widely used off-label in NICU. Our aim was to investigate its cerebral, cardiovascular and pulmonary effects as well as pharmacokinetics in an experimental model for neonates.MethodsFentanyl (5 µg/kg bolus immediately followed by a 90 minute infusion of 3 µg/kg/h) was administered to six mechanically ventilated newborn piglets. Cardiovascular, ventilation, pulmonary and oxygenation indexes as well as brain activity were monitored from T = 0 up to the end of experiments (T = 225–300 min). Also plasma samples for quantification of fentanyl were drawn.ResultsA “reliable degree of sedation” was observed up to T = 210–240 min, consistent with the selected dosing regimen and the observed fentanyl plasma levels. Unlike cardiovascular parameters, which were unmodified except for an increasing trend in heart rate, some of the ventilation and oxygenation indexes as well as brain activity were significantly altered. The pulmonary and brain effects of fentanyl were mostly recovered from T = 210 min to the end of experiment.ConclusionThe newborn piglet was shown to be a suitable experimental model for studying fentanyl disposition as well as respiratory and cardiovascular effects in human neonates. Therefore, it could be extremely useful for further investigating the drug behaviour under pathophysiological conditions.