The effects of dexamethasone and acyclovir on a cell culture model of delayed facial palsy

Otol Neurotol. 2014 Apr;35(4):712-8. doi: 10.1097/MAO.0000000000000231.

Abstract

Hypothesis: Pretreatment with antiherpetic medications and steroids decreases likelihood of development of delayed facial paralysis (DFP) after otologic surgery.

Background: Heat-induced reactivation of herpes simplex virus type 1 (HSV1) in geniculate ganglion neurons (GGNs) is thought to cause of DFP after otologic surgery. Antiherpetic medications and dexamethasone are used to treat DFP. Pretreatment with these medications has been proposed to prevent development of DFP.

Methods: Rat GGN cultures were latently infected with HSV1 expressing a lytic protein-GFP chimera. Cultures were divided into pretreatment groups receiving acyclovir (ACV), acyclovir-plus-dexamethasone (ACV + DEX), dexamethasone alone (DEX), or untreated media (control). After pretreatment, all cultures were heated 43°C for 2 hours. Cultures were monitored daily for reactivation with fluorescent microscopy. Viral titers were determined from culture media.

Results: Heating cultures to 43°C for 2 hours leads to HSV1 reactivation and production of infectious virus particles (59 ± 6.8%); heating cultures to 41°C showed a more variable frequency of reactivation (60 ± 40%), compared with baseline rates of 14.4 ± 5%. Cultures pretreated with ACV showed lower reactivation rates (ACV = 3.7%, ACV + DEX = 1.04%) compared with 44% for DEX alone. Viral titers were lowest for cultures treated with ACV or ACV + DEX.

Conclusion: GGN cultures harboring latent HSV1 infection reactivate when exposed to increased temperatures that can occur during otologic surgery. Pretreatment with ACV before heat provides prophylaxis against heat-induced HSV reactivation, whereas DEX alone is associated with higher viral reactivation rates. This study provides evidence supporting the use of prophylactic antivirals for otologic surgeries associated with high rates of DFP.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acyclovir / therapeutic use*
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Antiviral Agents / therapeutic use*
  • Cells, Cultured
  • Dexamethasone / therapeutic use*
  • Facial Paralysis / etiology*
  • Facial Paralysis / prevention & control*
  • Geniculate Ganglion / cytology
  • Hot Temperature
  • Neurons / drug effects
  • Otologic Surgical Procedures / adverse effects*
  • Polymerase Chain Reaction
  • Postoperative Complications / prevention & control*
  • Rats
  • Rats, Sprague-Dawley
  • Viral Load
  • Virus Activation / drug effects
  • Virus Latency

Substances

  • Anti-Inflammatory Agents
  • Antiviral Agents
  • Dexamethasone
  • Acyclovir