Cerebellar anomalies in congenital murine toxoplasmosis

Abstract

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.

The Importance of Toxoplasma Gondii Infection in Diseases Presenting With Headaches. Headaches and Aseptic Meningitis May Be Manifestations of the Jarisch-Herxheimer Reaction

“…Because T. gondii tachyzoites have special predilection to these anatomical structures, one cannot exclude that these eventually lethal clinical courses of IIH resulted from a complication of untreated recurrent reactivations of CT (Ryan et al, 1993). This suggestion may be supported by the fact that in congenital murine toxoplasmosis, coronal sections of the cerebrum revealed marked periventricular edema, subependymal nodules bulging into the ventricles, and loss of subependymal germinal cells (Stahl & Kaneda, 1998). One may therefore speculate that other forms of brain neoplasia, such as recurrent intracranial ependymoma and myxopapillary ependymoma presenting with or without intracranial hypertension (Drozdowski & Pogorzelski, 2005;Good et al, 2001;Labauge, Gros, Pages, Benezech, & Salvaing, 1984;Philippon, Poisson, & Bleibel, 1980;Tseng, Hsu, Jung, & Chen, 2004;Warnick et al, 1993), glioblastoma multiforme masquerading as PTC (Aroichane, Miller, & Eggenberger, 1993), gliomatosis (Weston & Lear, 1995), and gliomas associated with epilepsy (Schlehofer et al, 1999;Schwartzbaum et al, 2005), food production or processing (Schlehofer et al, 2005), or occupations of women in agricultural services and farming (Zheng, Cantor, Zhang, Keim, & Lynch, 2001), have been caused by chronic untreated inflammation process due to recurrent reactivation of latent CT.…”

Materno-FÅ“tal Transmission of Murine Toxoplasmosis after Oral Infection

“…These results are supported by those of Thouvenin et al, (1997) who showed that in mice infected by 20 cysts of the strain PRU on the 11 th day of gestation, the cerebral and pulmonary parasite loads were much greater than those of mice who were non pregnant. Likewise, the intravascular transfer of the parasite into the brain during a congenital transmission following infection of mice with T. gondii on the 7 th day of pregnancy, entails a number of inflammatory lesions in the foetus (Stahl and Kaneda, 1998). When infection preceded mating except for the two mice who died during pregnancy, the rest of the females were either not pregnant (6 mice) or they gave birth to viables litters (24 mice).…”

“…On the other hand, some stages in certain of these studies are devoted to this aspect and allow us to compare our results. Thus by inoculating cysts of T. gondii intraperitoneally into NYLAR mice on the 7 th day of gestation, Stahl et al, (2002) have shown a clear reduction in the number and survival of the neonates per pregnancy. Likewise, oral infection of nonimmunized BALB/c mice (control group) with 4 cysts of the strain P between the 10 th and 14th day of pregnancy has permitted to obtain a high percentage of infected litters by congenital transmission of the parasite (Elsaid et al, 2001).…”

“…In experimental toxoplasmosis, the mouse is often used as a model for immunologic (Eisenhauer et al, 1988;Chardes et al, 1990, Hafid et al, 1991as well as parasitologic (Dubey, 1998), pathophysiologic (Dubey, 1997;Zenner et al, 1998) and pharmacologic studies (Isamida et al, 1998). As for vertical transmission studies of the parasite using animals, there are a few studies done using the oocysts, cysts and trophozoites of different T. gondii strains in order to understand the mode of transmission and the consequences in the mother as well as in the foetus and the neonate (Stahl and Kaneda, 1998;Stahl et al, 2002). Several vaccination studies have also been done in this animal using different formes of the parasite as well as protein and nucleic acid extracts administered by the intraperitoneal, intradermal or nasal routes (Ali et al, 2003;Bonenfant et al, 200;Letscher-Bru et al, 2003;Hafid et al, 2004).…”

Congenital LCMV virus

“…Additional evidence suggesting a central role of the immune system in inducing developmental brain disorders can be seen by looking at the cerebellar pathology that results in animals neonatally infected with a range of pathogens. Cerebellar pathology has been described in many different neonatal/congenital infections including Tamiami virus, Borna virus and toxoplasmosis in the mouse, parvovirus infection in the hamster and cat, Fowl glioma inducing virus in the chicken, feline panleukopenia virus in kittens, Akabane Bunyviridae virus in calves, bovine virus diarrhea virus (BVDV) in pigs, hog cholera virus in hogs, and the virus that causes shaking mink syndrome in mink [214][215][216][217][245][246][247][248]. Not all of these viruses target the same neuronal population in the brain.…”