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

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.