Blood-brain barrier damage in experimental African trypanosomiasis

The nature of microglia fascinated many prominent researchers in the 19th and early 20th centuries, and in a classic treatise in 1932, Pio del Rio-Hortega formulated a number of concepts regarding the function of these resident macrophages of the brain parenchyma that remain relevant to this day. However, a renaissance of interest in microglia occurred toward the end of the 20th century, fueled by the recognition of their role in neuropathogenesis of infectious agents, such as human immunodeficiency virus type 1, and by what appears to be their participation in other neurodegenerative and neuroinflammatory disorders. During the same period, insights into the physiological and pathological properties of microglia were gained from in vivo and in vitro studies of neurotropic viruses, bacteria, fungi, parasites, and prions, which are reviewed in this article. New concepts that have emerged from these studies include the importance of cytokines and chemokines produced by activated microglia in neurodegenerative and neuroprotective processes and the elegant but astonishingly complex interactions between microglia, astrocytes, lymphocytes, and neurons that underlie these processes. It is proposed that an enhanced understanding of microglia will yield improved therapies of central nervous system infections, since such therapies are, by and large, sorely needed

show abstract

“…Later, the BBB is disrupted more diffusely (288). Astrocyte activation is one of the first signs of neurological involvement (162).…”

Section: Parasitesmentioning

confidence: 99%

Role of Microglia in Central Nervous System Infections

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Phenotypically, the glycoconjugate expression of the choroid epithelial and ventricular ependymal cells are such that particular viruses are bound and incorporated intracellularly (Ormerod and Raseroka 1988). Similarly, Trypanosoma brucei, the protozoan agent that causes African sleeping sickness, begins CNS offensive actions by penetrating and disorganizing CP (Philip et al 1994). Trypanosome injection into rodents or goats induces neuropathology akin to the human African trypanosomiasis syndrome (Darsaud et al 2003;Moulton 1986;Poltera et al 1980).…”

Section: Toxico-pathologic Considerations For Choroid Plexuscerebrospmentioning

confidence: 99%

The Distributional Nexus of Choroid Plexus to Cerebrospinal Fluid, Ependyma and Brain

et al. 2010

View full text Add to dashboard Cite

Bordering the ventricular cerebrospinal fluid (CSF) are epithelial cells of choroid plexus (CP), ependyma and circumventricular organs (CVOs) that contain homeostatic transporters for mediating secretion/reabsorption. The distributional pathway (''nexus'') of CP-CSF-ependyma-brain furnishes peptides, hormones, and micronutrients to periventricular regions. In disease/toxicity, this nexus becomes a conduit for infectious and xenobiotic agents. The sleeping sickness trypanosome (a protozoan) disrupts CP and downstream CSF-brain. Piperamide is anti-trypanosomic but distorts CP epithelial ultrastructure by engendering hydropic vacuoles; this reflects phospholipidosis and altered lysosomal metabolism. CP swelling by vacuolation may occlude CSF flow. Toxic drug tools delineate injuries to choroidal compartments: cyclophosphamide (vasculature), methylcellulose (interstitium), and piperazine (epithelium). Structurally perturbed CP allows solutes to penetrate the ventricles. There, CSF-borne pathogens and xenobiotics may permeate the ependyma to harm neurogenic stem cell niches. Amoscanate, an anti-helmintic, potently injures rodent ependyma. Ependymal/brain regions near CP are vulnerable to CSF-borne toxicants; this proximity factor links regional barrier breakdown to nearby periventricular pathology. Diverse diseases (e.g., African sleeping sickness, multiple sclerosis) take early root in choroidal, circumventricular, or perivascular loci. Toxicokinetics informs on pathogen, anti-parasitic agent, and auto-antibody distribution along the CSF nexus. CVOs are susceptible to plasma-borne toxicants/pathogens. Countering the physico-chemical and pathogenic insults to the homeostasis-mediating ventricle-bordering cells sustains brain health and fluid balance.

show abstract

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Lejon

Legros²,

Rosengren³

et al. 2001

The American Journal of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

Abstract. Concentrations of glial fibrillary acidic protein (GFAp) and light subunit neurofilament protein (NFL) in cerebrospinal fluid (CSF) were measured in patients with second-stage Trypanosoma brucei gambiense sleeping sickness. Correlations between GFAp and NFL in CSF as markers for astrogliosis and neurodegeneration, and clinical and biological data were investigated. Abnormal levels of GFAp and NFL were significantly associated with increasing CSF cell number and protein concentration, and with the absence of lymph nodes or the absence of trypanosomes in lymph node aspirate. A significant association was found between abnormal NFL and presence of trypanosomes in CSF, abnormal limb movements, difficulties in gait and coordination, and low Karnofsky index. By multivariate analysis, it was shown that increasing CSF cell number, increasing CSF protein concentration, and the absence of lymph nodes or the absence of trypanosomes in the lymph node aspirate were the best predictors for astrogliosis and neurodegeneration among the variables tested. These results demonstrate the importance of CSF cell count and protein determination in assessment of the severity of central nervous system involvement and reinforces the importance of laboratory diagnosis to assess the stage of the disease. The clinical symptoms studied were less useful in predicting astrogliosis or neurodegeneration.

show abstract

Blood-brain barrier damage in experimental African trypanosomiasis

Cited by 57 publications

References 15 publications

Role of Microglia in Central Nervous System Infections

Role of Microglia in Central Nervous System Infections

The Distributional Nexus of Choroid Plexus to Cerebrospinal Fluid, Ependyma and Brain

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

Contact Info

Product

Resources

About