Abstract
Hypoxic-ischemic encephalopathy (HIE) is detrimental to newborns and is associated with high mortality and poor prognosis. Thus, the primary aim of the present study was to determine whether glycine could (1) attenuate HIE injury in rats and hypoxic stress in PC12 cells and (2) downregulate mitochondria-mediated autophagy dependent on the adenosine monophosphate- (AMP-) activated protein kinase (AMPK) pathway. Experiments conducted using an in vivo HIE animal model and in vitro hypoxic stress to PC12 cells revealed that intense autophagy associated with mitochondrial function occurred during in vivo HIE injury and in vitro hypoxic stress. However, glycine treatment effectively attenuated mitochondria-mediated autophagy. Additionally, after identifying alterations in proteins within the AMPK pathway in rats and PC12 cells following glycine treatment, cyclosporin A (CsA) and 5-aminoimidazole-4-carboxamide-1-b-4-ribofuranoside (AICAR) were administered in these models and indicated that glycine protected against HIE and CoCl2 injury by downregulating mitochondria-mediated autophagy that was dependent on the AMPK pathway. Overall, glycine attenuated hypoxic-ischemic injury in neurons via reductions in mitochondria-mediated autophagy through the AMPK pathway both in vitro and in vivo.
Highlights
Hypoxic-ischemic injury in the neonatal brain is associated with detrimental and lethal consequences secondary to perinatal asphyxia [1]
In the paraformaldehyde-fixed brains of each group, edema was identified in the left hemisphere of hypoxicischemic encephalopathy (HIE) rats but glycine administration attenuated the affected area to a certain extent (Figure 1(e))
The number of functional neurons in Nissl-stained images was assessed to determine the effectiveness of glycine for treating or protecting neurons against hypoxic-ischemic injury
Summary
Hypoxic-ischemic injury in the neonatal brain is associated with detrimental and lethal consequences secondary to perinatal asphyxia [1]. Neonates diagnosed with hypoxicischemic encephalopathy (HIE) exhibit enhanced morbidity with poor clinical outcomes, which have increased awareness of this disorder worldwide [2]. Approximately 1–8 per 1000 live births are diagnosed with HIE, while 26 per 1000 live births suffered from this serious disease in developing countries [3]. The high cost and complicated therapeutic strategies associated with HIE typically result in difficulties maintaining adherence to treatment for patients and families. Severe cases of HIE often result in poor prognoses that include lifelong issues, like cerebral palsy, epilepsy, mental retardation, learning and cognitive disabilities, and hearing loss [4]. The development of inexpensive and effective treatment modalities is necessary to allow families to continue beneficial treatments that enhance the long-term prognoses of neonates
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