Changes in pH and myelin-related proteins expression in neonatal pigs post-hypoxic-ischemic injury

Neonatal hypoxic-ischemic encephalopathy (HIE) is a significant cause of developmental disorders and permanent central nervous system damage, with functional recovery closely linked to myelin sheath integrity. This study aimed to analyze the expression of pH and the voltage-gated proton channel (Hv1) in the brains of neonatal pigs with HIE at various time points, alongside changes in myelin-related proteins. MRI was used to localize the basal ganglia and assess pH changes post-hypoxia-ischemia, whereas immunofluorescence staining was used to evaluate Hv1, myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), and myelin-associated glycoprotein (MAG). Results indicated a correlation between pH and the expression of Hv1, MBP, and MOG. Under hypoxic-ischemic conditions, pH levels decreased, Hv1 expression increased, and myelin-associated proteins decreased. Over time, Hv1 expression declined whereas myelin-related protein expression increased with pH recovery. These findings suggest that following hypoxia-ischemia, extracellular acidosis can drive nicotinamide adenine dinucleotide phosphate oxidase (NOX)2 through Hv1 channel, and then cause damage to white matter, and as pH gradually recovers, the damaged myelin begins to repair, offering insights into the pathological mechanisms and potential treatment strategies for HIE in newborn pigs.NEW & NOTEWORTHY Newborn pigs with highly similar structure to human brain were selected as models to evaluate the short-term pathophysiological changes after hypoxic-ischemic encephalopathy (HIE). We studied the relationship between pH, voltage-gated proton channel (Hv1), and myelin-related proteins, and proved that the brain acidosis and myelin damage occurred after hypoxia-ischemia (HI). With the gradual recovery of pH, the injured myelin began to repair.