Lymphocytic Choriomeningitis Virus-Induced Mortality in Mice Is Triggered by Edema and Brain Herniation
Open accessAbstract
Although much is known about lymphocytic choriomeningitis virus (LCMV) infection and the subsequent immune response in its natural murine host, some crucial aspects of LCMV-mediated pathogenesis remain undefined, including the underlying basis of the characteristic central nervous system disease that occurs following intracerebral (i.c.) challenge. We show that the classic seizures and paresis that occur following i.c. infection of adult, immunocompetent mice with LCMV are accompanied by anatomical and histological changes that are consistent with brain herniation, likely of the uncal subtype, as a causative basis for disease and precipitous death. Both by water weight determinations and by magnetic resonance imaging of infected brain tissues, edema was detected only at the terminal stages of disease, likely caused by the leakage of cerebrospinal fluid from the ventricles into the parenchyma. Furthermore, death was accompanied by unilateral pupillary dilation, which is indicative of uncal herniation. While immunohistochemical analysis revealed periventricular inflammation and a loss of integrity of the blood-brain barrier (BBB), these events preceded seizures by 2 to 3 days. Moreover, surviving perforin knockout mice showed barrier permeability equivalent to that of moribund, immunocompetent mice; thus, BBB damage does not appear to be the basis of LCMV-induced neuropathogenesis. Importantly, brain herniation can occur in humans as a consequence of injuries that would be predicted to increase intracranial pressure, including inflammation, head trauma, and brain tumors. Thus, a mechanistic dissection of the basis of LCMV neuropathogenesis may be informative for the development of interventive therapies to prevent this typically fatal human condition.
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During LCMV meningitis, recruited CD8+ T cells and myelomonocytic cells damage meningeal vasculature and the walls of the ventricular system, causing severe edema and brainstem herniation.
“During this disease, recruited CD8+ T cells and myelomonocytic cells damage meningeal vasculature and the walls of the ventricular system, causing severe edema and brainstem herniation (154, 155).”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [155]
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- Authors
- Matullo, C. M., O'Regan, K. J., Hensley, H., Curtis, M., & Rall, G. F.
- Affiliations
- Fox Chase Cancer Center (US)
- Program in Immune Cell Development and Host Defense, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, Pennsylvania 19111
- Thomas Jefferson University (US)
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2010-01
- Volume
- 84
- Issue
- 1
- Pages
- 312-320
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC2798401
- OpenAlex
- W2101404690
- Cited by
- 27
- References
- 34
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 2 · 2022: 1 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2013: 2 · 2012: 6
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Virology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (P30CA006927)
- National Institute of Neurological Disorders and Stroke (R01NS060701, R01NS040500, R01 NS40500)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Vectors
- Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- lymphocytic choriomeningitis virus, brain herniation, uncal herniation, cerebral edema, central nervous system disorders, neuropathogenesis, blood-brain barrier integrity, perforin, cerebrospinal fluid leak, seizures, intracerebral infection, intracranial pressure, mouse model
- MeSH terms
- Animals, Blood-Brain Barrier, Edema, Encephalocele, Inflammation, Lymphocytic Choriomeningitis, Lymphocytic choriomeningitis virus, Magnetic Resonance Imaging, Mortality, Paresis, Seizures, Mice, Knockout, Mice, Perforin
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