Neurological damage in
Herpes simplex type 1
encephalitis results from neuronal cell death secondary to viral invasion, and from inflammatory changes and cerebral oedema secondary to the immune response to the virus.
Corticosteroids could have an important role in the management of
Herpes simplex encephalitis because their anti-inflammatory action reduces cerebral oedema. However their use has been limited by concerns that their immunosuppressive actions could increase viral replication and spread. The present study examined this issue in a rat model in which injection of HSV-1 into the cervical vagus nerve produced a well-defined focal
encephalitis, characterised by an orderly progression of the virus through central neural pathways connected with vagal afferent termination sites in the medulla oblongata. After injection of HSV-1, rats were treated twice a day, either with vehicle (saline, 400 microl i.p.), with
acyclovir (30 mg/kg i.p.), with
dexamethasone (5 mg/kg i.p.), or with both
acyclovir and
dexamethasone. Animals were sacrificed after 72 h, and viral load in different brain regions was quantified by computer-assisted measurement of the area occupied by immunohistochemical reaction product. Treatment with
acyclovir reduced viral load to 17 +/- 5% of the saline value (P < 0.01). After
dexamethasone treatment, the viral load (63 +/- 13% of the saline value) was also reduced (P < 0.05). Treatment with both
acyclovir and
dexamethasone reduced viral load to 26 +/- 8% of the saline value (P < 0.01 compared with saline, and P > 0.05 compared to
acyclovir alone). Our results confirm the effectiveness of
acyclovir in a new model of HSV-1
infection, and provide evidence that
corticosteroids do not inhibit the
antiviral action of
acyclovir. In addition
corticosteroids may decrease the extent of
infection in their own right. The acute time course studied in our model parallels the time course of acute
Herpes simplex encephalitis in humans. Our data suggests that
corticosteroids are not detrimental when combined with
acyclovir in the management of this condition.