Synaptic Injury in the Thalamus Accompanies White Matter Injury in HypoxiaIschemia-Mediated Brain Injury in Neonatal Rats

الملخص EN

The broad spectrum of disabilities caused by white matter injury (WMI) cannot be explained simply by hypomyelination.

Synaptic injury in the thalamus may be related to disabilities in WMI survivors.

Neuronal injury in the thalamus has been found most commonly in autopsy cases of preterm WMI.

We hypothesized that hypoxia/ischemia (HI) in neonatal rats results in synaptic abnormalities in the thalamus that contribute to disabilities in WMI survivors.

We examined changes in synapses in a neonatal rat model of HI-induced WMI.

Right common carotid artery ligation and hypoxia (8% oxygen for 2.5 hours (h)) were performed in three-day-old Sprague-Dawley rats.

We found HI rats performed worse in the Morris water maze test than sham rats, suggesting long-term cognition impairment after HI injury.

A loss of synapses in the thalamus accompanied by hypomyelination and oligodendrocytes (OLs) reduction was observed.

At the ultrastructural level, reductions in active zone (AZ) length and postsynaptic density (PSD) thickness were detected at 2 weeks after HI exposure.

Furthermore, increased expression of synaptophysin and PSD-95 in both groups was observed from 3 days (d) to 21 d after hypoxic/ischemic (HI) injury.

PSD-95 expression was significantly lower in HI rats than in sham rats from 14 d to 21 d after HI injury, and synaptophysin expression was significantly lower in HI rats from 7 d to 14 d after HI injury.

However, no significant difference in synaptophysin expression was observed between HI rats and sham rats at 21 d after HI injury.

The results demonstrated synaptic abnormalities in the thalamus accompanied by hypomyelination in WMI in response to HI exposure, which may contribute to the diverse neurological defects observed in WMI patients.

Although synaptic reorganization occurred as a compensatory response to HI injury, the impairments in synaptic transmission were not reversed.