Effect of Intranasally Administered Stem Cell–Derived Exosomes on Rat's Olfactory Bulb Histological Structure After Lead-Oxide Nanoparticle Administration

Abstract Lead is a common heavy metal used in a variety of products. We investigated the effect of lead-oxide nanoparticles (PbO-NPs) on the histological structure of the rat olfactory bulb (OB) and the potential therapeutic effect of stem cell–derived exosomes (EXOs). Forty male rats were included: 8 for EXO isolation and 32 were distributed into 4 groups: control, PbO-NPs group [intranasal (IN) 50 µL PbO-NPs/rat for 3 weeks], recovery group (PbO-NPs for 3 weeks and left for another 4 weeks), and PbO-NP-EXO (PbO-NPs for 3 weeks then IN EXO for another 3 weeks). After 7 weeks, olfactory behavioral tests were done before scarification. OBs were stained with hematoxylin and eosin, toluidine blue, and immunohistochemistry for synaptophysin (SYP), and ionized calcium-binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP). The results were confirmed by histomorphometry and statistical analysis. PbO-NPs and recovery groups showed a significant olfactory dysfunction, significant decrease in the thickness of OB layers and diameter of glomeruli, Nissl's granules of mitral cells and SYP immunostaining, and a significant increase in Iba-1 and GFAP expression compared with control rats. In PbO-NP-EXO, notable regaining of OB structure and function was obvious with reversal of most of the behavioral and morphometric findings compared with the untreated groups. IN EXO administration improved the structure and function of PbO-NP-induced OB neurotoxicity.