Biphalin, a dimeric opioid peptide, reduces neonatal hypoxia-ischemia brain injury in mice by the activation of PI3K/Akt signaling pathway.
J Chem Neuroanat
; 115: 101967, 2021 09.
Article
em En
| MEDLINE
| ID: mdl-33992725
ABSTRACT
Previous studies have demonstrated that the activation of delta opioid receptors is neuroprotective against neonatal hypoxia-ischemia (HI) brain injury. The aim of this study was to investigate the neuroprotective effects of biphalin, a dimeric opioid peptide, in a mouse model of neonatal HI and the underlying mechanisms. On postnatal day 10, mouse pups were subjected to unilateral carotid artery ligation followed by 1 h of hypoxia (10 % O2 in N2). For treatment, biphalin (5 mg/kg, 10 mg/kg, 20 mg/kg) was administered intraperitoneally immediately after HI. The opioid antagonist naloxone or phosphatidylinositol-3-kinase inhibitor Ly294002 was administered to determine the underlying mechanisms. Infarct volume, brain edema, phosphorylated Akt and apoptosis-related proteins levels were evaluated by using a combination of 2,3,5-triphenyltetrazolium chloride staining, brain water content and Western blotting at 24 h after HI. The long-term effects of biphalin were evaluated by brain atrophy measurement, Nissl staining and neurobehavioral tests at 3 weeks post-HI. Biphalin (10 mg/kg) significantly reduced the infarct volume and ameliorated brain edema. Biphalin also had long-term protective effects against the loss of ipsilateral brain tissue and resulted in improvements in neurobehavioral outcomes. However, naloxone or Ly294002 abrogated the neuroprotective effects of biphalin. Furthermore, biphalin treatment significantly preserved phosphorylated Akt expression, increased Bcl-2 levels, and decreased Bax and cleaved caspase 3 levels after HI. These effects were also reversed by naloxone and Ly294002 respectively. In conclusion, biphalin protects against HI brain injury in neonatal mice, which might be through activation of the opioid receptor/phosphatidylinositol-3-kinase/Akt signaling pathway.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encefalinas
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Transdução de Sinais
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Fármacos Neuroprotetores
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Fosfatidilinositol 3-Quinases
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Hipóxia-Isquemia Encefálica
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Proteínas Proto-Oncogênicas c-akt
Limite:
Animals
Idioma:
En
Revista:
J Chem Neuroanat
Assunto da revista:
ANATOMIA
/
NEUROLOGIA
/
QUIMICA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China