Blood-brain barrier function in cerebral malaria in Malawian children.

Abstract

Abstract. Cerebral malaria (CM) is a serious complication of Plasmodium falciparum infection. Binding of parasitized erythrocytes to cerebral endothelium plays a key role in disease pathogenesis. Central nervous system signs and symptoms (coma, seizures, raised intracranial pressure) predominate in African children, whereas in adults, multiorgan system failure is more common. In this study we investigated whether changes in blood-brain barrier (BBB) structure and function are compatible with the signs and symptoms observed in Malawian children with CM. Immunohistochemistry on autopsy brain tissues from eight cases of CM showed activation of endothelial cells and macrophages, and disruption of endothelial intercellular junctions in vessels containing sequestered parasitized erythrocytes, but no gross leakage of plasma proteins. Examination of the partition of albumin between circulating plasma and the cerebrospinal fluid from 72 cases of CM showed subtle but measurable changes compatible with impaired BBB function in malaria. These findings suggest that BBB breakdown occurs in areas of parasite sequestration in CM in African children.

Review Article: Blood-brain barrier in falciparum malaria*

“…The CSF albumin and IgG and IgM were not raised in Zairean children with CM compared with Swiss controls. However, in a more recent study from Malawi, the partition of albumin between circulating plasma and CSF showed subtle but measurable changes suggesting impairment of the BBB (Brown et al 2001). These findings have been confirmed in Kenyan children with CM (Mturi et al 2003) but the Kenyan study also found that the BBB was mildly impaired in children with malaria and seizures or those with a less severe degree of unconsciousness, suggesting that impairment of the BBB is not unique for CM.…”

“…This study found gaps between the ECs (Figure 3), with PRBC and non-PRBC in the brain parenchyma, but this only occurred in haemorrhages and there was no difference between those with CM and non-CM cases. Immunochemistry has shown distribution of the cell junction proteins occludin, vinculin and ZO-1 were altered in Vietnamese adults (Brown et al 1999) and Malawian children with CM (Brown et al 1999(Brown et al , 2001). In the perivascular space, there was a widespread macrophage activation suggesting that these cells had been exposed to plasma proteins.…”

Effect of malaria components on blood mononuclear cells involved in immune response

“…TGF-β mRNA and protein were expressed in CM post-mortem brain tissue from Malawian children infected with P. falciparum malaria [46] . TGF-β was also elevated in the CSF of Vietnamese patients with CM [47] . Furthermore, Thai patients with malaria had low levels of serum TGF-β, which were noted to increase after treatment with artesunate and mefloquine [48] .…”

Pediatric Cerebral Malaria: A Scourge of Africa

“…In autopsy-derived samples from children with CM, there are conflicting results with one group showing loss of tight junction proteins and a lack of transendothelial leakage of fibrinogen, whereas a more recent report shows significant leakage of fibrinogen into the brain parenchyma [26,27]. Assessment of the integrity of the BBB can be determined in vivo with the use of retinal fluorescein angiography.…”