Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses.

TitleMouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses.
Publication TypeJournal Article
Year of Publication2020
AuthorsLaval, K, Maturana, CJ, Enquist, LW
JournalJ Vis Exp
Date Published2020 06 14
KeywordsAlphaherpesvirinae, Animals, Disease Models, Animal, Ganglia, Spinal, Herpesviridae Infections, Hindlimb, Inflammation, Mice, Mice, Inbred C57BL, Peripheral Nervous System Diseases, Sciatic Nerve, Virus Replication

<p>This protocol describes a footpad inoculation model used to study the initiation and development of neuroinflammatory responses during alphaherpesvirus infection in mice. As alphaherpesviruses are main invaders of the peripheral nervous system (PNS), this model is suitable to characterize the kinetics of viral replication, its spread from the PNS to CNS, and associated neuroinflammatory responses. The footpad inoculation model allows virus particles to spread from a primary infection site in the footpad epidermis to sensory and sympathetic nerve fibers that innervate the epidermis, sweat glands, and dermis. The infection spreads via the sciatic nerve to the dorsal root ganglia (DRG) and ultimately through the spinal cord to the brain. Here, a mouse footpad is inoculated with pseudorabies virus (PRV), an alphaherpesvirus closely related to herpes simplex virus (HSV) and varicella-zoster virus (VZV). This model demonstrates that PRV infection induces severe inflammation, characterized by neutrophil infiltration in the footpad and DRG. High concentrations of inflammatory cytokines are subsequently detected in homogenized tissues by ELISA. In addition, a strong correlation is observed between PRV gene and protein expression (via qPCR and IF staining) in DRG and the production of pro-inflammatory cytokines. Therefore, the footpad inoculation model provides a better understanding of the processes underlying alphaherpesvirus-induced neuropathies and may lead to the development of innovative therapeutic strategies. In addition, the model can guide research on peripheral neuropathies, such as multiple sclerosis and associated viral-induced damage to the PNS. Ultimately, it can serve as a cost-effective in vivo tool for drug development.</p>

Alternate JournalJ Vis Exp
PubMed ID32597850
Grant ListR01 NS033506 / NS / NINDS NIH HHS / United States
R01 NS060699 / NS / NINDS NIH HHS / United States