Pharmacological Neuroprotection of the Preterm Brain: Current Evidence and Perspectives.

Despite improvements in viability, the long-term neurodevelopmental outcomes of preterm babies remain serious concern as a significant percentage of these infants develop neurological and/or intellectual impairment, and they are also at increased risk of psychiatric illnesses later in life. The current challenge is to develop neuroprotective approaches to improve adverse outcomes in preterm survivors. The purpose of this review was to provide an overview of the current evidence on pharmacological agents targeting the neuroprotection of the preterm brain. Among them, magnesium sulfate, given antenatally to pregnant women with imminent preterm birth before 30 to 34 weeks of gestation, as well as caffeine administered to preterm infants after birth, exhibited neuroprotective effects for human preterm brain. Erythropoietin treatment of preterm infants did not result in neuroprotection at 2 years of age in two out of three published large randomized controlled trials; however, long-term follow-up of these infants is needed to come to definite conclusions. Further studies are also required to assess whether melatonin, neurosteroids, inhaled nitric oxide, allopurinol, or dietary supplements (omega-3 fatty acids, choline, curcumin, etc.) could be implemented as neuroprotectants in clinical practice. Furthermore, other pharmacological agents showing promising signs of neuroprotective efficacy in preclinical studies (growth factors, hyaluronidase inhibitors or treatment, antidiabetic drugs, cannabidiol, histamine-H3 receptor antagonists, etc.), as well as stem cell- or exosomal-based therapies and nanomedicine, may prove useful in the future as potential neuroprotective approaches for human preterm brain. KEY POINTS: · Magnesium and caffeine have neuroprotective effects for the preterm brain.. · Follow-up of infants treated with erythropoietin is needed.. · Neuroprotective efficacy of several drugs in animals needs to be shown in humans..

Paraoxonase (PON)-1 activity in septic neonates: One more arrow in the quiver of biomarkers of neonatal sepsis?

Paraoxonase-1 (PON-1), a calcium ion-dependent high-density lipoprotein (HDL)-associated enzyme, has been proposed as a negative acute phase reactant biomarker in animal and human adult studies. The aim of this study was to evaluate the value of PON-1 activity in the diagnosis and monitoring of neonatal sepsis. Serum PON-1 activity, as paraoxonase and arylesterase, was prospectively studied in 48 septic neonates and matched controls. PON-1 activity was decreased at the acute phase of sepsis in comparison with values at recovery and values in controls. Paraoxonase or arylesterase at enrollment correlated significantly with serum Amyloid-A, CRP and IL-6 and could also discriminate septic than non-septic neonates. In conclusion, our results are promising regarding the role of PON-1 as a biomarker of neonatal sepsis. Larger studies are needed to validate the clinical utility of PON-1 in neonatal medicine.

Bilateral sudden sensorineural hearing loss caused by alcohol abuse and heroin sniffing.

Objective. Acute or chronic heroin abuse has been associated with various central neurologic pathologies and, occasionally, with peripheral nervous system damage. The effect of heroin on hearing has not been adequately documented, although several cases with sudden hearing loss owed to heroin abuse have been reported. We present a young male with bilateral sudden sensorineural hearing loss, following heroin sniffing and alcohol consumption. Methods. Our patient underwent a detailed clinical and audiological evaluation, including auditory brainstem responses and otoacoustic emission. Routine laboratory blood tests and imaging studies were performed. Results. The patient was treated with corticosteroids and magnesium, resulting in complete restoration of hearing after one month. Conclusion. Sudden hearing loss owed to heroin abuse is usually curable, following adequate treatment.