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Table 2 Evidence of blood–brain barrier (BBB) impairment in animal models with cerebral malaria (CM)

From: Host matrix metalloproteinases in cerebral malaria: new kids on the block against blood–brain barrier integrity?

Animal source

Plasmodium strain

Method to evaluate BBB integrity

Degree of impairment

Reference

Rhesus monkey (Macaca mulatta)

P. knowlesi

Examination of movement of proteins across the BBB by radiometric and fluorimetric methods

Increase of BBB permeability

[109111]

Rhesus monkey (Macaca mulatta)

P. fragile

Electron microscopy, immunohistochemical analysis (CD36, thrombospondin, ICAM-1), formation of rosettes

Parasitized red blood cells sequestration and adherence to endothelial cells in the cerebral microvessels, neurological symptoms similar to humans

[112]

Rhesus monkey (Macaca mulatta)

P. coatneyi

Clinical observation

Anemia, coagulopathy, and renal and metabolic dysfunction

[113]

Rhesus monkey (Macaca mulatta)

P. coatneyi

Tissue samples from the brain (cortex and white matter of the cerebrum, cerebellum, and midbrain) collected for quantitation of mRNA expression of cytokines, adhesion molecules, and iNOS

Expression of pro-inflammatory and T helper-1 cytokines, adhesion molecules, and iNOS appears to predominate in the cerebellum of infected rhesus monkeys

[114]

A/J and CBA/H mice

P. berghei (ANKA)

Detection of the movement of the dye Evans blue, radioisotope labelled albumin and erythrocytes

Breakdown of BBB

[115]

mouse

P. berghei (K173)

Histochemical and histological evaluation of cerebral lesions and their distribution

Progressive deterioration of BBB integrity

[116118]

CBA/T6, Balb/c and DBA/2 J mice

P. berghei (ANKA and K173)

Evaluation of neurological signs (ataxia, hemiplegia and coma)

Increased permeability of BBB

[119]

Mouse

P. berghei (ANKA)

Multimodal magnetic resonance techniques (imaging, diffusion, perfusion, angiography, spectroscopy).

BBB breakdown

[120]

CM- resistant BALB/c mice

P. berghei (ANKA)

Evaluation of pro-inflammatory cytokines produced

BBB breakdown

[121]

C57BL/6 and BALB/c mice

P. berghei (NK65)

Histopathological analysis of cerebral tissue

Increased permeability of BBB

[122]

TNF-α-and LT-α-deficient mice

P. berghei (ANKA)

Histochemical and histological evaluation

Neurological signs of CM, associated with perivascular brain haemorrhage in TNF-α -/- mice; completely resistant to CM in LT-α -/- mice

[47]

Mouse

P. berghei (ANKA)

Examination of the outcome of TGF-β and TNF-α production in the context of splenocyte apoptosis

Critical balance between TGF-β and TNF-α might have a key role in BBB breakdown

[123]

Different murine models: CBA/CaJ and Swiss Webster mice (CM sensitive), Balb/c and A/J mice (CM resistant)

P. berghei (ANKA) P. yoelii (17XL) P. berghei (NK65) and P. yoelii (YM)

Examination of histopathological alterations, BBB dysfunction, or neurological signs

CM related to the opening of paracellular-junctional and transcellular-vesicular fluid transport pathways at the neuroimmunological BBB

[124]