Fig. 3.

Intranasaladministration ofLPS – the proposed pathways of propagation of intranasal inflammation to the brain.

LPS administered via the nasal cavity can activate Toll-like receptor 4 (TLR4) expressed on olfactory epithelial cells, stimulating these cells to produce inflammatory cytokines. Olfactory epithelial cells can also recruit resident immune cells such as macrophages, dendritic cells and mucosal lymphocytes to the inflammatory site (Lane, 2009). Intranasal LPS can activate microglia and astrocytes in the olfactory bulb (OB) located in the CNS and the inflammatory response initiated by olfactory epithelial cells could propagate to the OB through cell to cell interaction between olfactory sensory neurons embedded in olfactory epithelium and neuronal dendrites in the OB (Hasegawa-Ishii et al., 2017; He et al., 2016b). The neurons in the OB project to various regions in the brain such as olfactory cortex (OC) which can propagate inflammation to the substantia nigra (SN) (Doty, 2012). Exacerbated neuroinflammation in the SN could cause degeneration of dopaminergic neurons as outlined in Fig. 1.