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Experimental schizencephaly induced by Kilham strain of mumps virus: pathogenesis of cleft formation
T Takano1, S Takikita, M Shimada
1Department of Pediatrics, Shiga University of Medical Sciences, Seta, Otsu, Japan.
Abstract:
The pathogenesis of cleft formation in schizencephaly was analyzed by examining the brain lesions produced by the infection of the Kilham strain of mumps virus during the period of neuronal migration in hamsters. Mumps virus antigen was detected in the neuroepithelial cells within the ventricular zone, the choroid plexus in the lateral ventricles, and vimentin-immunoreactive radial glial fibers. The main pathological findings were cerebral hemorrhage, neuronal necrosis, microsulci on the cerebral cortex and cleft formation through the entire thickness of the cerebral mantle. The clefts seen in these experiments were lined by embryonal elements such as neuroepithelial cells and germinal cells. Based on these results and the original definition by Yakovlev and Wadsworth, the following two conclusions were suggested. First, the mumps virus localized to the neuroepithelial cells within the ventricular zone and the radial glial fibers may induce a destructive process and subsequent anomalous neuronal migration, resulting in cleft formation. Second, the formation of the ventricular cleft extending to the pial surface, which should be complete before the cortical infolding appears, is necessary in order to produce the characteristic cleft in schizencephaly which is associated with the pial-ependymal seam.
Insights
Mumps virus infection during development can cause schizencephaly, a brain malformation. This study reveals how the virus damages developing brain cells, leading to abnormal neuronal migration and cleft formation.
Area of Science:
- Neuroscience
- Developmental Biology
- Virology
Background:
- Schizencephaly is a congenital brain malformation characterized by clefts in the cerebral hemispheres.
- The precise pathogenesis of schizencephaly, particularly the role of viral infections, remains incompletely understood.
Purpose of the Study:
- To investigate the pathogenesis of cleft formation in schizencephaly using a viral infection model.
- To identify the specific cellular targets and pathological mechanisms induced by mumps virus during critical developmental periods.
Main Methods:
- Induction of brain lesions in hamsters by infecting them with the Kilham strain of mumps virus during neuronal migration.
- Detection of mumps virus antigen using immunohistochemistry.
- Analysis of pathological findings including hemorrhage, neuronal necrosis, and malformations.
Main Results:
- Mumps virus antigen was detected in neuroepithelial cells, choroid plexus, and radial glial fibers.
- Pathological findings included cerebral hemorrhage, neuronal necrosis, microsulci, and full-thickness cleft formation.
- Experimental clefts were lined by embryonal elements, including neuroepithelial and germinal cells.
Conclusions:
- Mumps virus localized in the ventricular zone and radial glia may trigger destructive processes and aberrant neuronal migration, leading to cleft formation.
- The formation of a ventricular cleft extending to the pial surface before cortical folding is crucial for developing characteristic schizencephalic clefts associated with pial-ependymal seams.