Cerebellar anomalies in congenital murine toxoplasmosis.
Gravid Nya:NYLAR mice, infected with Toxoplasma gondii on gestation day 7, experienced embryo resorptions, abortions, stillbirths, and a reduction in average litter size by one-third. Postnatally, all congenitally infected pups showed growth retardation, cachexia, and hind limb weakness. Some pups developed necrotic petechiae on the ears and tail, and a blood-tinged nasal discharge. Coronal sections of the cerebellum at age 1 month revealed developmental abnormalities including: persistence of remnants of an external granular layer; fragmented and disoriented Bergmann glial foot processes; numerous ectopic granule cells stranded in the molecular layer; focal disorganization and edema of the Purkinje cell layer; and thinning of the internal granular layer. Our working hypothesis is that the cerebellar anomalies originated with parasite invasion of the fetal vascular endothelium leading to vasculitis and microcirculatory dysfunction, perivascular edema, perfusion impairment, and tissue anoxia. In the cerebellar folia, the cellular migration defects are attributed to edema-induced swelling and fragmentation of the Bergmann glial foot processes that guide migrating neurons, whereas the focal loss of Purkinje and granule cells is ascribed to hypoxia-ischemia. Although Toxoplasma cysts were detected in the cerebellum, morphologic evidence of parasite association with neuropathology was not obtained.
Stahl
W
W
Department of Infectious Diseases, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan. stahl@is.icc.u-tokai.ac.jp
Sekiguchi
M
M
Kaneda
Y
Y
D000818:Animals; D064026:Calbindins; D002531:Cerebellum / Q000737:chemistry / Q000473:pathology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D064030:S100 Calcium Binding Protein G / Q000032:analysis / Q000276:immunology; D009418:S100 Proteins / Q000032:analysis / Q000276:immunology; D014122:Toxoplasma / Q000472:pathogenicity; D014124:Toxoplasmosis, Animal / Q000473:pathology*; D016781:Toxoplasmosis, Cerebral / Q000473:pathology*; D014125:Toxoplasmosis, Congenital / Q000473:pathology*
D064026:Calbindins; D005904:Glial Fibrillary Acidic Protein; D064030:S100 Calcium Binding Protein G; D009418:S100 Proteins