In an experimental rat protocol, I am observing frequent vacuoles in the cerebral neurons, almost exclusively in the nuclei. They occur much more frequently in some experimental groups compared to others, but within groups they occur in both control and exposed animals. They are present almost exclusively in the cortex and hippocampus, and repeatedly present in certain specific areas of the cortex. The rats received whole body perfusion with 4% PFA. No other neuropathology is seen on H&E, with the exception of one animal.

On TEM, the vacuoles contain vesicular structures reminiscent of liposomes or autophagosomes, and are often multilamellar reminiscent of a lamellar body or late stage autophagosomes. Cytoplasmic organelles appear healthy.

We have looked at LAMP1 and Lamin B IFA (no nuclear puncta), and LC3 (multifocal linear and punctal nuclear uptake in affected regions, but seen in cells both with and without vacuoles).

I am trying to figure out the pathophysiology of these vacuoles. The TEM appearance is not an artifact I have seen before or can find in the literature, but I also struggle to explain why the vacuoles are present in both control and exposed animals if they have a true significance. Does anyone have any ideas or have seen this before?