Central Nervous System Involvement in Experimental Infection With Leishmania (Leishmania) Amazonensis

Abstract

Abstract. We describe the pathologic alterations of the central nervous system (CNS) observed in experimental tegumentary leishmaniasis in BALB/c and Swiss mice. The mice were subcutaneously infected with 10 4 amastigotes of Leishmania (Leishmania) amazonensis. Animals were killed and brains were removed for histologic and immunocytochemical studies. Histologic examination showed that 66.6% of infected mice had a discrete hyperemia and inflammatory infiltrate in the meninges, composed of mononuclear cells and neutrophils with no detectable parasites. However, parasitized macrophages were detected in the cerebral parenchyma, as well as mast cells, lymphocytes, and polymorphonuclear cells. Necrosis in the cerebral parenchyma was also observed. Confocal fluorescence microscopy showed that CD8 + T lymphocytes are the major component of the inflammatory infiltrate in the CNS. In addition to these cells, CD4 + , CD11b, and dendritic cells are present, in small numbers, in the inflammatory processes of the CNS. Thus, L. amazonensis is able to cross the blood-brain barrier and cause significant pathologic changes in the CNS.

Neurologic Manifestations ofLeishmania spp.Infection

“…Reports of neuro-inflammation associated with natural and experimental VL infection [1,33], as well as the presence of Immunoglobulin in aqueous humor and cerebrospinal fluid (CSF) [15] suggest a disruption of the blood-brain barrier (BBB), and the bloodcerebrospinal fluid barrier underlies the CNS manifestation of disease. The BBB functions to exclude microscopic objects and large hydrophilic molecules, and is achieved by endothelial cell specializations including tight junctions between cells, a specialized basal lamina surrounding the vessels in the brain, and an ensheathment of the vessels made of astrocytic endfeet [11].…”

“…Despite this, there is a wealth of clinical information on neurological effects of leishmaniasis in animal models [14,15,37] and human case studies [21], which indicates that both central nervous system (CNS) and ocular manifestations are common and often underreported. There are historical [5] and recent reports [1] of both CNS and ocular alterations with visceral leishmaniasis (VL), particularly. In addition to CNS manifestations, there have been studies indicating localized peripheral nerve deficits with cutaneous leishmaniasis [25].…”

Leishmania amastigotes in the central nervous system of a naturally infected dog

“…The researchers showed nervous parenchyma infection with presence of amastigotes, thus demonstrating the ability of these organisms to reach the brain, and it was suggested that parasites might have arrived to the CNS via loaded leukocytes. 1 In CL, no amastigotes have been observed in CSF. However, in human beings, the migration of parasites into the CSF was reported in a 10-year-old boy suffering from visceral leishmaniasis for more than 2 years.…”

“…20 Microbes seem to use several routes to enter the CNS including pathogen-directed penetration of choroid plexus epithelial cells, leading to the CSF; cerebral capillary endothelial cells, leading to the brain parenchyma; disrupting the blood-brain or blood-CSF barriers; and, finally, being transported across these barriers within infected leukocytes. 18 Researchers in a previous study 1 infected mice with subcutaneous injection of L. amazonensis amastigotes. The researchers showed nervous parenchyma infection with presence of amastigotes, thus demonstrating the ability of these organisms to reach the brain, and it was suggested that parasites might have arrived to the CNS via loaded leukocytes.…”

Destiny and Intracellular Survival ofLeishmania amazonensisin Control and Dexamethasone-treated Glial Cultures: Protozoa-specific Glycoconjugate Tagging and TUNEL Staining

“…In addition to these relatively well-known parasites that invade the neural tissue, others, such as Leishmania , have become objects of concern by virtue of reports on the presence of anti-Leishmania antibodies and/or Leishmania amastigotes in the cerebrospinal fluid or of meningeal affection in naturally infected humans and animals (Garcia-Alonso et al 1996;Nieto et al 1996;Prasad and Sen 1996;Vinuelas et al 2001) plus transmission from infected patients to experimental animals under conditions that simulate needle sharing (Morillas-Marquez et al 2002). More-over, recent work has shown parasitized macrophages in the cerebral parenchyma in experimental tegumentary leishmaniasis in mice (Abreu-Silva et al 2003).…”