The experimental squalene encephaloneuropathy in the rat.
Accumulation of squalene in the CNS is observed after administration of tellurium and squalene has been proposed to be a mediator of tellurium encephaloneuropathy. The aim of this study was to investigate the effects of squalene on the central and peripheral nervous systems in rat at the ultrastructural level. Squalene was administered at a dose of 20 g/kg body weight, once daily for 4 days, and the animals were sacrificed 7 days and 30 days after the initiation of the experiment. After 7 days a mild swelling of mitochondria and dilation of the Golgi complex cisterns in few neurons in the cerebral cortex and hippocampus were observed. The swelling of astrocytes and their processes was also seen. Some myelin sheaths in the cerebral white matter were disintegrated. In the peripheral nervous system (the sciatic nerve), a damage of the Schwann cells, a destruction of the myelin sheaths, and lipid-like deposits between myelin lamellae causing a secondary compression of axons were present. Squalene administration caused a stimulation of fibroblast to synthesize collagen and an activation of macrophages in the perineurium. After 30 days, the lipid-like material was present in some neurons as well as in the myelin sheaths in the central nervous system. Endothelial cells were hypertrophic and a few demonstrated features of apoptosis. Endothelial cell hypertrophy caused a narrowing of vessel lumen associated with an aggregation of blood morphological elements. Disturbances in myelination and swelling of astrocytic processes persisted in the central nervous system. In the peripheral nervous system, lipid-like deposits were localized in some fibroblasts and extracellularly between the collagen fibers in the perineurium. In conclusion, our electron microscopic studies indicate that squalene produces characteristic pathological changes both in the central and peripheral nervous systems. However, these alterations differ in some aspects (changes in endothelia, accumulation of lipid-like material) from the known features of tellurium encephaloneuropathy.
The Laboratory of the Ultrastructure of the Nervous System, Medical Research Center, Polish Academy of Sciences, Warsaw.
B
B
Gajkowska
M
M
Smialek
R P
RP
Ostrowski
P
P
Piotrowski
M
M
Frontczak-Baniewicz
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000648:ultrastructure; D001921:Brain / Q000187:drug effects* / Q000648:ultrastructure; D001927:Brain Diseases / Q000139:chemically induced* / Q000473:pathology; D007279:Injections, Subcutaneous; D008055:Lipids / Q000032:analysis; D008297:Male; D008854:Microscopy, Electron; D015388:Organelles / Q000187:drug effects / Q000648:ultrastructure; D017933:Peripheral Nervous System / Q000187:drug effects* / Q000648:ultrastructure; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013185:Squalene / Q000633:toxicity*; D013691:Tellurium / Q000633:toxicity
D008055:Lipids; D013185:Squalene; D013691:Tellurium