Mouse Model of Bell's palsy Induced by Reactivation of Herpes Simplex Virus Type 1

Abstract

In order to investigate the mechanism of Bell's palsy, we developed an animal model of facial nerve paralysis induced by the reactivation of herpes simplex virus type 1 (HSV-1). Eight weeks after recovery from facial nerve paralysis caused by inoculation with HSV-1, the mice were treated with auricular skin scratch at the site of the previous inoculation, or with intraperitoneal injection of anti-CD3 monoclonal antibody (mAb), or combination of both procedures. No mice developed facial nerve paralysis when they were treated with either auricular scratch or mAb injection alone. In contrast, 20% of mice developed facial nerve paralysis with the combined treatment. With one exception, no mouse treated with either auricular scratch or mAb injection showed HSV-I DNA in their facial nerve tissue, whereas 4 out of 6 mice receiving both treatments showed HSV-1 DNA on day 10 after treatment. Histopathological findings showed neuronal degeneration in the geniculate ganglion and demyelination of the facial motor nerve in paralyzed mice. These findings suggest that a combination of stimuli, local skin irritation, and general immunosuppression is essential for successfully inducing facial nerve paralysis in mice with latent HSV-1 infection.

Role of T-lymphocyte subsets in facial nerve paralysis owing to the reactivation of herpes simplex virus type 1

“…However, the paralysis was caused by a primary infection of the virus and we suspected that the pathogenesis was dissimilar to that of Bell's palsy. More recently [4], we verified that, after recovery from primary paralysis, HSV-1 latency was established in the GG of mice on the side that had received the initial viral inoculum. Furthermore, we developed an animal model of facial paralysis that involved the reactivation of HSV-1 via local skin irritation and general immune suppression.…”

“…The HSV-1 reactivation procedure involved auricular scratching and immunosuppression [4]. Eight weeks after recovery from the primary paralysis, the skin surface of the right auricle where HSV-1 had been inoculated previously was scratched with a 27-gauge needle, and the mice (n 0/69) were injected intraperitoneally with 200 mg of either anti-CD4 mAb (anti-CD4 model; n 0/46) or anti-CD8 mAb (anti-CD8 model; n 0/23).…”

“…The anti-CD4 (GK1.5) and anti-CD8 (2.43) mAbs were produced from TIB207 and TIB210 hybridoma cells (American Type Culture Collection, Rockville, MD), respectively. The mAbs were purified as previously described [4]. The mice were observed daily for the appearance of facial nerve paralysis and changes in general condition.…”

“…injection of anti-CD4 mAb (n 0/4) and anti-CD8 mAb (n 0/4) depleted peripheral CD4'/ and CD8'/ T cells, respectively. The numbers of CD4'/ and CD8'/ T cells in peripheral blood were counted using a FACScan analyzer (Becton-Dickinson, Mansfield, MA) and a Microcell Counter (CC-130A; Sysmex, Kobe, Japan) and then calculated using a previously described method [4]. As a control, we used four mice that had been injected with the same volume of PBS intraperitoneally.…”

Facial paralysis induced by ear inoculation of herpes simplex virus in rat

“…Bell's palsy is mainly caused by the reactivation of HSV-1 [1]. In the mouse model, Takahashi et al successfully produced facial paralysis in mice by reactivation of HSV-1 [23]. A combination of local skin irritation and T-cell suppression using an anti-CD3 monoclonal antibody induced the reactivation of HSV-1 and facial palsy.…”