Spread of Trypanosoma brucei to the nervous system: Early attack on circumventricular organs and sensory ganglia

Abstract

The distribution of Trypanosoma brucei brucei in the nervous system of experimentally infected Sprague-Dawley rats and BALB/c and deer mice was examined with immunohistochemical techniques. The trypanosomes showed an early invasion in areas lacking a so-called blood-brain or blood-nerve barrier, i.e., in sensory ganglia and circumventricular organs including the area postrema, pineal gland, and median eminence. This distribution of trypanosomes may relate to the origin of cardinal symptoms of the disease, e.g., sensory disturbances, nausea, disturbed circadian rhythm, and neuroendocrinological dysfunctions. Trypanosome infections in rodents may provide a model for studies of how an infectious agent or factors released by the immune response may relatively selectively interfere with these functionally defined regions of the nervous system.

Cerebral vessel laminins and IFN-γ define Trypanosoma brucei brucei penetration of the blood-brain barrier

“…brucei brucei invasion of the brain was found to be confined to circumventricular organs at 6 days p.i., as described previously in mice and rats (2), while penetration of the parenchyma commenced around 13 days after infection in WT mice. Similar to our observations in rats (3), parasite invasion occurred by the penetration of intracerebral vessels and not by the spread of parasites from the circumventricular organs through the cerebrospinal fluid, since few parasites were observed close to the ventricles.…”

Biological data and clinical symptoms as predictors of astrogliosis and neurodegeneration in patients with second-stage Trypanosoma brucei gambiense sleeping sickness.

“…Parasites probably enter the brain via areas with a reduced blood-brain barrier and spread into cerebrospinal fluid (CSF) and stromal spaces via the subarachnoid spaces to the perivascular extensions that pass into the brain. [1][2][3][4] This is associated with chronic meningitis that progresses to encephalitis and is accompanied by extensive perivascular cuffing, infiltration and activation of plasma cells, Mott cells, T-cells, and astrocytes, and by neuronal degeneration. 1,[5][6][7][8] Changes in the composition of CSF reflect events in the CNS.…”

Detection of light subunit neurofilament and glial fibrillary acidic protein in cerebrospinal fluid of Trypanosoma brucei gambiense-infected patients.

“…The meningoencephalitis observed in African trypanosomiasis is characterized by parasite invasion of the meninges and choroid plexus, infiltration of the leptomeninges and perivascular areas by IgM producing plasma cells, Mott cells, and T helper/inducer cells, diffuse microglial hyperplasia, astrogliosis in the white matter, and demyelination of neurons. [2][3][4][5][6] A correct stage determination is indispensable since it is directly related to the choice of an optimal treatment with minimal risk for the patient. This is currently carried out by examining the cerebrospinal fluid (CSF) for cell number, protein concentration, and presence of trypanosomes.…”