Role of Antioxidants in Neonatal Hypoxic–Ischemic Brain Injury: New Therapeutic Approaches

Abstract

Hypoxic–ischemic brain damage is an alarming health and economic problem in spite of the advances in neonatal care. It can cause mortality or detrimental neurological disorders such as cerebral palsy, motor impairment and cognitive deficits in neonates. When hypoxia–ischemia occurs, a multi-faceted cascade of events starts out, which can eventually cause cell death. Lower levels of oxygen due to reduced blood supply increase the production of reactive oxygen species, which leads to oxidative stress, a higher concentration of free cytosolic calcium and impaired mitochondrial function, triggering the activation of apoptotic pathways, DNA fragmentation and cell death. The high incidence of this type of lesion in newborns can be partly attributed to the fact that the developing brain is particularly vulnerable to oxidative stress. Since antioxidants can safely interact with free radicals and terminate that chain reaction before vital molecules are damaged, exogenous antioxidant therapy may have the potential to diminish cellular damage caused by hypoxia–ischemia. In this review, we focus on the neuroprotective effects of antioxidant treatments against perinatal hypoxic–ischemic brain injury, in the light of the most recent advances.

Purmorphamine Attenuates Neuro-Inflammation and Synaptic Impairments After Hypoxic-Ischemic Injury in Neonatal Mice via Shh Signaling

“…The capacity for PUR to exert antioxidant effects in HI, as revealed by significantly decreasing HI-induced ROS levels, was consistent with a previous study (Hu et al, 2016). A number of antioxidants, including allopurinol, erythropoietin, resveratrol, and omega-3 fatty acids, have been shown to exhibit neuroprotective properties in different animal models of perinatal HI brain injury (Peeters-Scholte et al, 2003;Arteaga et al, 2017;Revuelta et al, 2017). In this FIGURE 8 | Effects of PUR on brain atrophy and behavioral changes following HI insult.…”

Photobiomodulation preconditioning prevents cognitive impairment in a neonatal rat model of hypoxia‐ischemia

“…Due to the deprivation of oxygen and glucose occurring within the brain, brain injury in HIE is usually characterized by delayed neuronal cell death in the cortex and the hippocampus . Neuronal cell death can cause several types of severe neurological dysfunction such as impairments in hearing, learning, behavioral disability, attention deficits, blindness or even death .…”

Might Bilirubin Serve as a Natural Antioxidant in Response to Neonatal Encephalopathy?

“…Free radicals are continuously generated in newborns even in the absence of any pathology and, all the more so in the presence of pathology. The brain is most susceptible to oxidative injury because of its rapid metabolic rate and oxygen consumption, its high content of easily oxidized membrane lipids, 14 and its limited antioxidant mechanisms. In fact, most natural antioxidant defense systems are not fully mature in the early days of life.…”