Inhalation of growth factors and apo-transferrin to protect and repair the hypoxic-ischemic brain

Clausi, Mariano Guardia; Paez, Pablo M.; Pasquini, Laura; Pasquini, Juana M.

doi:10.1016/j.phrs.2016.01.010

Cited by 13 publications

(6 citation statements)

References 40 publications

(47 reference statements)

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“…Interestingly, at the highest dose of plasmid used, TF not only protected photoreceptors from cell death but also prevented the RPE barrier breakdown, as witnessed by reduced albumin leakage, preserved RPE structure, and reduced retinal inflammation. The anti-inflammatory properties of TF have already been shown in the ischemic brain [63], but the protective role of TF on the RPE barrier had not been evidenced previously, confirming that TF might have additional non-iron-mediated effects as shown by transcriptomic analysis of TF effects in a retinal detachment model [6]. The superiority of TF over CA, a well-known antioxidant, is in line with this observation.…”

Section: Discussionsupporting

confidence: 68%

Transferrin Non-Viral Gene Therapy for Treatment of Retinal Degeneration

Bigot¹,

Gondouin²,

Bénard³

et al. 2020

Pharmaceutics

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Dysregulation of iron metabolism is observed in animal models of retinitis pigmentosa (RP) and in patients with age-related macular degeneration (AMD), possibly contributing to oxidative damage of the retina. Transferrin (TF), an endogenous iron chelator, was proposed as a therapeutic candidate. Here, the efficacy of TF non-viral gene therapy based on the electrotransfection of pEYS611, a plasmid encoding human TF, into the ciliary muscle was evaluated in several rat models of retinal degeneration. pEYS611 administration allowed for the sustained intraocular production of TF for at least 3 and 6 months in rats and rabbits, respectively. In the photo-oxidative damage model, pEYS611 protected both retinal structure and function more efficiently than carnosic acid, a natural antioxidant, reduced microglial infiltration in the outer retina and preserved the integrity of the outer retinal barrier. pEYS611 also protected photoreceptors from N-methyl-N-nitrosourea-induced apoptosis. Finally, pEYS611 delayed structural and functional degeneration in the RCS rat model of RP while malondialdehyde (MDA) ocular content, a biomarker of oxidative stress, was decreased. The neuroprotective benefits of TF non-viral gene delivery in retinal degenerative disease models further validates iron overload as a therapeutic target and supports the continued development of pEY611 for treatment of RP and dry AMD.

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Section: Discussionsupporting

confidence: 68%

Transferrin Non-Viral Gene Therapy for Treatment of Retinal Degeneration

Bigot¹,

Gondouin²,

Bénard³

et al. 2020

Pharmaceutics

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“…Apo-transferrin has been shown to be essential for oligodendrocyte maturation and myelination in vitro and in vivo in animal studies, whereas following intranasal administration, it can reach distal areas of the brain. 108 The intranasal administration of apo-transferrin and different growth factors, such as insulin-like growth factor-1 (IGF-1) or epidermal growth factor (EGF), provided neuroprotection against hypoxic-ischemic or LPS-induced brain injury in neonatal mice and rats. 108 109 110 111 Intranasal IGF-1 also reduced germinal matrix hemorrhages in a preterm rat pup model, 112 whereas the selective overexpression of human EGF receptor in oligodendrocyte lineage cells or the intranasal administration of heparin-binding EGF immediately after injury in very preterm mice decreased oligodendroglia death, enhanced generation of new oligodendrocytes, and promoted functional recovery.…”

Section: Future Perspectives For Pharmacological Neuroprotection Of H...mentioning

confidence: 99%

“…108 The intranasal administration of apo-transferrin and different growth factors, such as insulin-like growth factor-1 (IGF-1) or epidermal growth factor (EGF), provided neuroprotection against hypoxic-ischemic or LPS-induced brain injury in neonatal mice and rats. 108 109 110 111 Intranasal IGF-1 also reduced germinal matrix hemorrhages in a preterm rat pup model, 112 whereas the selective overexpression of human EGF receptor in oligodendrocyte lineage cells or the intranasal administration of heparin-binding EGF immediately after injury in very preterm mice decreased oligodendroglia death, enhanced generation of new oligodendrocytes, and promoted functional recovery. 113 Vascular endothelial growth factor was also shown to play a protective role against excitotoxicity in immature mice brain.…”

Section: Future Perspectives For Pharmacological Neuroprotection Of H...mentioning

confidence: 99%

Pharmacological Neuroprotection of the Preterm Brain: Current Evidence and Perspectives

Siahanidou

Spiliopoulou

2020

Am J Perinatol

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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

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“…Apo‐transferrin (aTf) and THs have different and well‐documented effects on the central nervous system (CNS). THs promote the differentiation of OPC, while aTf induces the commitment of neural stem cells (NSC) toward the oligodendroglial lineage and OPC proliferation, and favors OLG maturation (Dugas, Ibrahim, & Barres, 2012; El‐Tahry et al, 2016; Guardia Clausi, Paez, Pasquini, & Pasquini, 2016; Guardia Clausi, Pasquini, Soto, & Pasquini, 2010; Marziali, Garcia, & Pasquini, 2015; Silvestroff, Franco, & Pasquini, 2012). Previous results by our group showed that THs are necessary early on in OLG development to induce aTf synthesis, which favors the expression of THR receptor α (THRα) and OLG differentiation.…”

Section: Introductionmentioning

confidence: 99%