Neuroprotective Effects of Diabetes Drugs for the Treatment of Neonatal Hypoxia-Ischemia Encephalopathy

Poupon-Bejuit, Laura; Rocha‐Ferreira, Eridan; Thornton, Claire; Hagberg, Henrik; Rahim, Afidah Abdul

doi:10.3389/fncel.2020.00112

Cited by 10 publications

(7 citation statements)

References 117 publications

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“…Oxygen glucose deprivation (OGD) model is widely used as a feasible in vitro model for ischemic stroke (Yang et al, 2019 ; Poupon-Bejuit et al, 2020 ). Hence, the OGD model was applied to examine the underlying potential cellular mechanisms in the present study.…”

Section: Methodsmentioning

confidence: 99%

Ambroxol Upregulates Glucocerebrosidase Expression to Promote Neural Stem Cells Differentiation Into Neurons Through Wnt/β-Catenin Pathway After Ischemic Stroke

Zhang

Yang

et al. 2021

Front. Mol. Neurosci.

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Ischemic stroke has been becoming one of the leading causes resulting in mortality and adult long-term disability worldwide. Post-stroke pneumonia is a common complication in patients with ischemic stroke and always associated with 1-year mortality. Though ambroxol therapy often serves as a supplementary treatment for post-stroke pneumonia in ischemic stroke patients, its effect on functional recovery and potential mechanism after ischemic stroke remain elusive. In the present study, the results indicated that administration of 70 mg/kg and 100 mg/kg enhanced functional recovery by virtue of decreasing infarct volume. The potential mechanism, to some extent, was due to promoting NSCs differentiation into neurons and interfering NSCs differentiation into astrocytes through increasing GCase expression to activate Wnt/β-catenin signaling pathway in penumbra after ischemic stroke, which advanced basic knowledge of ambroxol in regulating NSCs differentiation and provided a feasible therapy for ischemic stroke treatment, even in other brain disorders in clinic.

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Section: Methodsmentioning

confidence: 99%

Ambroxol Upregulates Glucocerebrosidase Expression to Promote Neural Stem Cells Differentiation Into Neurons Through Wnt/β-Catenin Pathway After Ischemic Stroke

Zhang

Yang

et al. 2021

Front. Mol. Neurosci.

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“…121 Other diabetes drugs and derivatives could be also a promising option as neuroprotective agents. 118,122 Histamine-H3 Receptor Antagonists Histamine, an endogenous biogenic amine acts as a neurotransmitter in the brain and contributes to modulate several functions including motor behavior and cognition. 123 Among all histamine receptors expressed in the brain, H3 receptor is the most prominent and has an inhibitory role in preoligodendrocyte differentiation.…”

Section: Antidiabetic Drugsmentioning

confidence: 99%

“…121 Other diabetes drugs and derivatives could be also a promising option as neuroprotective agents. 118 122…”

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

confidence: 99%

“…There is evidence that medications used for the treatment of type 2 diabetes mellitus have neuroprotective properties in animal models of neonatal hypoxic-ischemic encephalopathy. 118 Metformin, a commonly used oral antidiabetic drug, improved remyelination and ameliorated cognitive impairments in hypoxia-ischemia neonatal rats. 119 Metformin promoted neurogenesis, inhibited neuronal apoptosis, suppressed neuroinflammation, and ameliorated the blood-brain barrier breakdown.…”

Section: Antidiabetic Drugsmentioning

confidence: 99%

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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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“…Specifically, hypothermia reduces the overall systemic inflammatory and metabolic responses to injury in addition to having specific neuroprotective effects [ 12 , 13 , 14 , 15 , 16 ]. Therefore, other anti-inflammatory approaches may offer clinically valid alternatives or adjunctive therapeutic effects to hypothermia for the treatment of HIE [ 17 , 18 , 19 ]. Inter-alpha Inhibitor Proteins (IAIPs) are a family of plasma proteins found abundantly in mammals including rats, sheep, and humans and are thought to play a significant role in regulating inflammation [ 20 , 21 , 22 , 23 , 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Juvenile or Adolescent Working Memory Experience and Inter-Alpha Inhibitor Protein Treatment after Neonatal Hypoxia-Ischemia

et al. 2020

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Hypoxic-Ischemic (HI) brain injury in the neonate contributes to life-long cognitive impairment. Early diagnosis and therapeutic interventions are critical but limited. We previously reported in a rat model of HI two interventional approaches that improve cognitive and sensory function: administration of Inter-alpha Inhibitor Proteins (IAIPs) and early experience in an eight-arm radial water maze (RWM) task. Here, we expanded these studies to examine the combined effects of IAIPs and multiple weeks of RWM assessment beginning with juvenile or adolescent rats to evaluate optimal age windows for behavioral interventions. Subjects were divided into treatment groups; HI with vehicle, sham surgery with vehicle, and HI with IAIPs, and received either juvenile (P31 initiation) or adolescent (P52 initiation) RWM testing, followed by adult retesting. Error rates on the RWM decreased across weeks for all conditions. Whereas, HI injury impaired global performance as compared to shams. IAIP-treated HI subjects tested as juveniles made fewer errors as compared to their untreated HI counterparts. The juvenile group made significantly fewer errors on moderate demand trials and showed improved retention as compared to the adolescent group during the first week of adult retesting. Together, results support and extend our previous findings that combining behavioral and anti-inflammatory interventions in the presence of HI improves subsequent learning performance. Results further indicate sensitive periods for behavioral interventions to improve cognitive outcomes. Specifically, early life cognitive experience can improve long-term learning performance even in the presence of HI injury. Results from this study provide insight into typical brain development and the impact of developmentally targeted therapeutics and task-specific experience on subsequent cognitive processing.

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Neuroprotective Effects of Diabetes Drugs for the Treatment of Neonatal Hypoxia-Ischemia Encephalopathy

Cited by 10 publications

References 117 publications

Ambroxol Upregulates Glucocerebrosidase Expression to Promote Neural Stem Cells Differentiation Into Neurons Through Wnt/β-Catenin Pathway After Ischemic Stroke

Ambroxol Upregulates Glucocerebrosidase Expression to Promote Neural Stem Cells Differentiation Into Neurons Through Wnt/β-Catenin Pathway After Ischemic Stroke

Pharmacological Neuroprotection of the Preterm Brain: Current Evidence and Perspectives

Effects of Juvenile or Adolescent Working Memory Experience and Inter-Alpha Inhibitor Protein Treatment after Neonatal Hypoxia-Ischemia

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