Altered plasma-type gelsolin and amyloid-β in neonates with hypoxic-ischaemic encephalopathy under therapeutic hypothermia

Abstract

Hypoxic-ischemic encephalopathy (HIE) is a severe neonatal complication responsible for ∼23% of all neonatal deaths. Also, 30-70% of these patients will suffer lifetime disabilities, including learning impairment, epilepsy or cerebral palsy. However, biomarkers for HIE screening, or monitoring disease progression are limited. Herein, we sought to evaluate the clinical usefulness of plasma-type gelsolin (pGSN) and amyloid-beta (Aβ) 40 and 42 as prognostic biomarkers for HIE. pGSN has been previously suggested as a feasible marker in other brain injuries and amyloid-beta 40 and 42 are classically assessed in neurodegenerative diseases. However, to our knowledge, they have not been previously assessed in HIE patients. We have analyzed plasma pGSN and Aβ 40 and 42 levels in 55 newborns (16 controls, 16 mild and 23 moderate-severe HIE) at birth, during 72 h of therapeutic hypothermia, a gold-standard treatment for HIE, and 24 h after hypothermia. Aβ levels were lower in HIE patients, and pGSN levels were progressively reduced in mild and moderate-severe HIE patients. The fact that pGSN reductions could predict the severity of HIE and significantly correlated with the time to undergo hypothermia supports the prognostic value of plasmatic pGSN. Further studies are warranted to investigate the role of pGSN in neonatal HIE.

Erythropoietin Improves Atrophy, Bleeding and Cognition in the Newborn Intraventricular Hemorrhage

“…On the other hand, plasma gelsolin levels were significantly reduced in mice after GM-IVH, as previously reported (Segado-Arenas et al, 2018). Plasma gelsolin is a feasible peripheral marker of central complications and low plasma gelsolin levels have been associated with poor outcomes in adult brain hemorrhagic alterations (Chou et al, 2011), in premature infants (Kose et al, 2014) and other newborn complications (Benavente-Fernandez et al, 2018). EPO treatment significantly restores plasma gelsolin levels, suggesting that its positive effects at central level are also detected in the periphery and reinforcing further studies on the utility of plasma gelsolin as a prognostic tool.…”

“…Spine and neuronal loss were limited, and overspread small vessel damage and inflammation were reduced, resulting in the preservation of learning and memory abilities. Interestingly, plasma gelsolin levels, as a feasible peripheral marker of GM-IVH-induced damage, previously observed in other brain disorders (Xu et al, 2012;Peng et al, 2015;Benavente-Fernandez et al, 2018), recovered after EPO administration.…”

“…Therefore, PTI with very low weight birth are more susceptible to local hemorrhage ( Perlman, 2009 ). The short- and long-term neurodevelopmental complications in the PTI with severe or even mild GM-IVH are a major concern, since these kids are at high risk of neurosensory impairment, developmental delay, cerebral palsy, deafness, psychomotor alterations or cerebral palsy ( Ballabh, 2010 ; Mukerji et al, 2015 ; Benavente-Fernandez et al, 2018 ).…”

Cytokine and chemokine responses to injury and treatment in a nonhuman primate model of hypoxic-ischemic encephalopathy treated with hypothermia and erythropoietin

“…Though none have yet translated to clinical practice, a number of promising biomarkers of HIE remain in development. The most well-described is perhaps plasma Tau, 44 with metabolomic analyses of the tryptophan/kynurenine pathway, 45 plasma-type gelsolin, 46 serum neurofilament light, 47 serum 24S-hydroxycholesterol, 48 and plasma osteopontin 49 also receiving recent attention in various models or types of neonatal and pediatric brain injury and holding significant promise for investigation in both large animal models and human infants with HIE. Though the search for circulating biomarkers in HIE still continues, physiological measurements such as continuous EEG or amplitudeintegrated EEG (aEEG) are already being implemented clinically and have shown a robust ability to assist in long-term outcome prediction in the era of TH, [50][51][52] as well as having significant promise for automated analysis and combination with other physiological measurements such as near-infra-red spectroscopy (NIRS) to examine neurovascular coupling.…”

Hypoxic-Ischemic Brain Injury after Perinatal Asphyxia as a Possible Factor in the Pathology of Alzheimer’s Disease

“…The results of these studies suggest that there is a close relationship between tau protein and perinatal brain injury (92)(93)(94)(95). It has also been noticed that the level of tau protein in the serum of newborns with HIE has a prognostic value regarding their long-term neurodevelopmental prognosis (96). According to the available literature, only one study has evaluated the usefulness of β-amyloid 40 and 42 in serum as a prognostic biomarker in HIE (96).…”