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Perinatal Hypoxic-Ischemic Encephalopathy and Neuroprotective Peptide Therapies: A Case for Cationic Arginine-Rich Peptides (CARPs)

1
Perron Institute for Neurological and Translational Science, Nedlands, WA 6009, Australia
2
School of Health Sciences and Institute for Health Research, The University of Notre Dame Australia, Fremantle, WA 6160, Australia
3
Department of Neurosurgery, Sir Charles Gairdner Hospital, QEII Medical Centre, Nedlands, WA 6009, Australia
4
Centre for Neuromuscular and Neurological Disorders, The University of Western Australia, Nedlands, WA 6009, Australia
*
Author to whom correspondence should be addressed.
Brain Sci. 2018, 8(8), 147; https://doi.org/10.3390/brainsci8080147
Received: 28 June 2018 / Revised: 25 July 2018 / Accepted: 1 August 2018 / Published: 7 August 2018
(This article belongs to the Special Issue The Treatment of Neonatal Hypoxic-Ischemic Encephalopathy)
Perinatal hypoxic-ischemic encephalopathy (HIE) is the leading cause of mortality and morbidity in neonates, with survivors suffering significant neurological sequelae including cerebral palsy, epilepsy, intellectual disability and autism spectrum disorders. While hypothermia is used clinically to reduce neurological injury following HIE, it is only used for term infants (>36 weeks gestation) in tertiary hospitals and improves outcomes in only 30% of patients. For these reasons, a more effective and easily administrable pharmacological therapeutic agent, that can be used in combination with hypothermia or alone when hypothermia cannot be applied, is urgently needed to treat pre-term (≤36 weeks gestation) and term infants suffering HIE. Several recent studies have demonstrated that cationic arginine-rich peptides (CARPs), which include many cell-penetrating peptides [CPPs; e.g., transactivator of transcription (TAT) and poly-arginine-9 (R9; 9-mer of arginine)], possess intrinsic neuroprotective properties. For example, we have demonstrated that poly-arginine-18 (R18; 18-mer of arginine) and its D-enantiomer (R18D) are neuroprotective in vitro following neuronal excitotoxicity, and in vivo following perinatal hypoxia-ischemia (HI). In this paper, we review studies that have used CARPs and other peptides, including putative neuroprotective peptides fused to TAT, in animal models of perinatal HIE. We critically evaluate the evidence that supports our hypothesis that CARP neuroprotection is mediated by peptide arginine content and positive charge and that CARPs represent a novel potential therapeutic for HIE. View Full-Text
Keywords: hypoxic-ischemic encephalopathy; hypoxia-ischemia; birth asphyxia; neuroprotection; cationic arginine-rich peptides; animal models hypoxic-ischemic encephalopathy; hypoxia-ischemia; birth asphyxia; neuroprotection; cationic arginine-rich peptides; animal models
MDPI and ACS Style

Edwards, A.B.; Anderton, R.S.; Knuckey, N.W.; Meloni, B.P. Perinatal Hypoxic-Ischemic Encephalopathy and Neuroprotective Peptide Therapies: A Case for Cationic Arginine-Rich Peptides (CARPs). Brain Sci. 2018, 8, 147.

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