Neuroplasticity After Hypoxic-Ischemic Brain Injury in Neonatal Pigs Based on Time-Dependent Behavior of 1H-MRS-Tau Protein and Synaptic Associated Proteins and Synaptic Structure Analysis

This study investigated the effects of hypoxic-ischemic (HI) injury on neonatal neuroplasticity using the following approaches: Magnetic Resonance Spectroscopy (¹H-MRS) imaging to analyze dynamic changes in tau protein levels, immunofluorescence staining to evaluate synaptophysin (SYP), neurocan (Neu), and tau protein, and utilizing transmission electron microscopy (TEM) to examine synaptic ultrastructure at multiple time points. A total of 59 healthy neonatal pigs were included, with 10 in the control group and 43 in the HI model group. The results demonstrated that SYP immunostaining intensity peaked at 6-12 h after HI before declining. Neu expression exhibited an initial decrease, followed by a transient increase and subsequent reduction, reaching its lowest level at 6-12 h after HI. Tau protein levels increased initially after HI, peaked at 24-48 h after HI, and subsequently decreased. SYP was negatively correlated with Neu with a correlation coefficient of -0.877. SYP was not correlated with Tau, neither was Neu with Tau. Compared with the control group, the number of synaptic vesicles decreased, and Post-Synaptic Density (PSD) thickness increased 6-12 h after HI. At 12-24 h after HI, the number of synaptic vesicles increased, and PSD thickness slightly decreased. At 24-48 h after HI, the vesicle number decreased, PSD became thinner, interrupting continuity, mitochondria swelled, and mitochondrial cristae blurred and disappeared. The findings suggest that the expression of Tau, SYP, and Neu is linked to alterations in synaptic and myelin structures, reflecting varying aspects of neural plasticity following HI injury.