Researchers may have uncovered a novel treatment pathway in patients with neurological antibiotic-refractive Lyme disease symptoms, according to a recent study published by Parthasarathy in Frontiers in Immunology. Previous research has determined that, in response to live Borrelia burgdorferi, fibroblast growth factor receptors (FGFR) may contribute to inflammatory mediator output from primary rhesus microglia. However, nonviable B burgdorferi may have potentially greater pathogenicity as live bacteria in central and peripheral nervous system tissues. In the recent study, researchers used rhesus frontal cortex and dorsal root ganglion tissue explants to examine whether live or nonviable B burgdorferi could induce FGFR expression; they also analyzed the bacteria’s neuronal and astrocyte localization. They discovered that FGFR2 was the most prevalently expressed receptor in the rhesus frontal cortex tissue explants, followed by FGFR3 and then FGFR1. Nonviable B burgdorferi upregulated FGFR3 more frequently than live bacteria; live bacteria upregulated FGFR1 more frequently than nonviable bacteria; and FGFR2 was least modulated by either bacterium. The researchers noted that FGFR1 showed higher expression in astrocytes, whereas FGFR2 and FGFR3 showed higher expression in neurons. For dorsal root ganglion tissue explants, FGFR1, FGFR2, and FGFR3 receptors were expressed but could not be distinguished from medium controls using immunofluorescence. The researchers also assessed whether FGFR inhibitors could reduce inflammatory output and apoptosis in response to live or nonviable bacteria. They found that the FGFR1 inhibitor PD166866 downregulated inflammation and apoptosis in the rhesus frontal cortex and dorsal root ganglion tissue explants in response to live or nonviable B burgdorferi. The FGFR3 inhibitor AZD4547 downregulated inflammation and apoptosis in the rhesus frontal cortex and dorsal root ganglion tissue explants in response to live bacteria; but with sonicated remnants, this effect was observed in 50% (n = 1/2) of the rhesus frontal cortex tissue explants and 67% (n = 2/3) of the dorsal root ganglion tissue explants. The researchers revealed that CCL2 and interleukin 6 were the most downregulated mediators in rhesus frontal cortex tissue explants, and CXCL8 and interleukin 6 were the most downregulated mediators in dorsal root ganglion tissue explants. The study authors concluded: “Our findings open the door to new research approaches that can help us support patients [experiencing] the lasting effects of Lyme disease. [W]e hope to develop treatments that can improve the quality of life for those affected by this debilitating condition.”