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2,3-Diphosphoglyceric Acid Alleviating Hypoxic-Ischemic Brain Damage through p38 MAPK Modulation.

Jiawei Ni1, Jing Zhao1, Haocong Chen1

  • 1Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.

International Journal of Molecular Sciences
|August 29, 2024
PubMed
Summary

2,3-Diphosphoglyceric acid (2,3-DPG) shows neuroprotective effects against neonatal hypoxic-ischemic encephalopathy (HIE). This metabolite reduces brain damage, apoptosis, and oxidative stress, offering a potential new therapy for HIE.

Keywords:
2,3-Diphosphoglyceric acidMAPKOGD/Rhypoxic-ischemic encephalopathyneuronal apoptosis

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Pediatrics

Background:

  • Neonatal hypoxic-ischemic encephalopathy (HIE) causes significant brain damage and mortality globally.
  • The role of 2,3-Diphosphoglyceric acid (2,3-DPG) in neuroprotection against hypoxic-ischemic brain damage (HIBD) is not fully understood.

Purpose of the Study:

  • To investigate the neuroprotective potential of 2,3-DPG in neonatal hypoxic-ischemic brain damage (HIBD).

Main Methods:

  • In vitro and in vivo models of hypoxia-ischemia (HI) and oxygen-glucose deprivation/reperfusion (OGD/R).
  • Administration of 2,3-DPG in rat models of HIBD.
  • Analysis of apoptosis markers (Bax, Bcl-2, cleaved-caspase 3).
  • Assessment of oxidative stress, mitochondrial damage, brain edema, and infarct volume.
  • RNA-sequencing (RNA-seq) to analyze pathway modulation (p38 MAPK).

Main Results:

  • 2,3-DPG administration reduced neuronal apoptosis by downregulating Bax and cleaved-caspase 3, and upregulating Bcl-2.
  • 2,3-DPG alleviated oxidative stress and mitochondrial damage.
  • In rats, 2,3-DPG decreased brain edema and infarct volume by suppressing apoptosis and neuroinflammation.
  • RNA-seq confirmed 2,3-DPG protects against neuronal apoptosis via the p38 MAPK pathway.

Conclusions:

  • 2,3-DPG demonstrates significant neuroprotective effects against HIBD.
  • 2,3-DPG mitigates neuronal apoptosis, oxidative stress, and inflammation.
  • 2,3-DPG emerges as a promising therapeutic candidate for HIE.