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Spread of herpes simplex virus to the cerebrospinal fluid and the meninges in experimental mouse encephalitis
R H Boerman1, A C Peters, B R Bloem
1Department of Neurology, University Hospital Leiden, The Netherlands.
Abstract:
The development of the inflammatory response within the brain, meninges and cerebrospinal fluid (CSF) compartment has been studied for the first time simultaneously in experimental herpes simplex virus (HSV) encephalitis after inoculation via the cornea. Two major viral pathways were found from the eye to the brain: one through the trigeminal nerve to the brain stem and one through the nasolacrimal duct to the olfactory system. Viral antigen was found to be present in the CNS before there were clinical signs or cellular infiltration of brain tissue. Subsequently, the virus spread to all parts of the trigeminal brain stem complex. This phenomenon was accompanied by severe inflammation of the meninges covering the trigeminal root near its entry into the brain stem. The meninges near the entry of the olfactory fila also contained antigen. However, HSV-1 did not spread along meningeal rami of the trigeminal nerve and, consequently, is--at least in this experimental model--not a route to reach the inferior frontal and temporal lobes. The development of CSF changes followed the histopathological development of meningitis and encephalitis closely. HSV-DNA could be detected in the CSF from day 4 post inoculation (p.i.) and HSV-1-specific immunofluorescence in CSF cells was convincingly present on day 5 p.i.; on the same days (4 and 5 p.i.) inflammatory cells were found in apposition to infected cells in the brain. We postulate that HSV is carried to the CSF by infected leukocytes rather than a direct spread to the CSF by simple extension of the encephalitic process to the meningeal surface.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
This study reveals two main pathways for herpes simplex virus (HSV) to reach the brain from the eye, causing encephalitis. Inflammation and viral DNA in cerebrospinal fluid (CSF) appear after initial brain infection.
Area of Science:
- Neuroscience
- Virology
- Immunology
Background:
- Herpes simplex virus (HSV) encephalitis is a serious neurological condition.
- Understanding the early spread of HSV within the central nervous system (CNS) is crucial for treatment.
Purpose of the Study:
- To simultaneously investigate the inflammatory response in the brain, meninges, and cerebrospinal fluid (CSF) during experimental HSV encephalitis.
- To identify the primary viral pathways from the eye to the CNS.
Main Methods:
- Experimental inoculation of the cornea with HSV in a model system.
- Tracking viral antigen, DNA, and inflammatory cell infiltration in the CNS, meninges, and CSF.
- Histopathological analysis of brain tissue and meninges.
Main Results:
- Identified two distinct viral entry routes to the brain: via the trigeminal nerve and the nasolacrimal duct/olfactory system.
- Viral antigen detected in the CNS prior to clinical signs or significant cellular infiltration.
- Inflammation in the meninges and changes in CSF closely followed encephalitis development, with HSV DNA detectable by day 4 post-inoculation.
Conclusions:
- HSV spreads to the brain through specific neural pathways, with early CNS presence before overt symptoms.
- Cerebrospinal fluid (CSF) changes reflect the progression of meningitis and encephalitis.
- Infected leukocytes likely transport HSV to the CSF, rather than direct spread from meningeal surfaces.