In vitro study of malaria parasite induced disruption of blood–brain barrier

Treeratanapiboon, Lertyot; Psathaki, Katherina; Wegener, Joachim; Galla, Hans‐Joachim; Udomsangpetch, Rachanee

doi:10.1016/j.bbrc.2005.07.151

Cited by 25 publications

(15 citation statements)

References 19 publications

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“…Parasite proteins were also shown to induce disruption of endothelial barrier function in a Src-family kinase-dependent manner, but surprisingly not the intact infected red blood cells [59]. Yet another mechanism for modulation of the endothelium was identified whereby endothelial permeability was increased following interaction with PBMCs which were previously exposed to parasite proteins [60].…”

Section: Indirect Activation Of Ecsmentioning

confidence: 97%

Host response to cytoadherence inPlasmodium falciparum

Chakravorty

Hughes

Craig

2008

Biochemical Society Transactions

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Cytoadherence of PRBCs (Plasmodium falciparum-infected red blood cells) to host endothelium has been associated with pathology in severe malaria, but, despite extensive information on the primary processes involved in the adhesive interactions, the mechanisms underlying the disease are poorly understood. Endothelial cells have the ability to mobilize immune and pro-adhesive responses when exposed to both PRBCs and TNF (tumour necrosis factor). In addition, there is also an up-regulation by PRBCs and TNF and a concurrent down-regulation of a range of genes involved in inflammation and cell death, by PRBCs and TNF. We propose that the balance between positive and negative regulation will contribute to endothelial pathology during malarial infection. Apposition of PRBCs has been shown by a number of groups to activate signalling pathways. This is dependent, at least in part, on the cytoadherence characteristics of the invading isolate, such that the avidity of the PRBC for the receptor on host endothelium is proportional to the level of activation of the signalling pathways. An understanding of the post-adhesive processes produced by cytoadherence may help us to understand the variable pathology seen in malaria and to design appropriate therapies to alleviate severe disease.

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Section: Indirect Activation Of Ecsmentioning

confidence: 97%

Host response to cytoadherence inPlasmodium falciparum

Chakravorty

Hughes

Craig

2008

Biochemical Society Transactions

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“…Consistently in various types of human brain endothelium, including HMBEC primary cultures and HBEC-5i or hCMEC/D3 cell lines, iRBCs were also shown to increase ICAM-1 expression [93,99,104,105], to reduce TEER [56,101,102], to alter tight junction expression and distribution [56,105], and to enhance BBB permeability to 70-kDa dextran [101]. Interestingly, platelets were suggested to play a key role in iRBC-dependent increase in BBB permeability, releasing microparticles and causing cell apoptosis in TNF-α- and LT-α-activated HBEC-5i [101].…”

Section: Introductionmentioning

confidence: 99%

“…As discussed below and summarized in Table 1, evidence showing differential phenotypes between neural and non-neural endothelial cells after co-culture with Plasmodium iRBCs comes from several in vitro studies [56,93,99-108]. …”

Section: Introductionmentioning

confidence: 99%

“…First, the effects of P. falciparum infection were investigated in a BBB model of cultured primary porcine brain capillary endothelial cells (PBCECs) [99]. In this study, membrane-associated malaria antigens obtained from lysed P. falciparum schizont-iRBCs increased endothelial E-selectin and ICAM-1 expression, reduced the trans-endothelial electrical resistance (TEER), and promoted the disruption of tight junctions, indicative of increased BBB permeability.…”

Section: Introductionmentioning

confidence: 99%

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

Polimeni

Prato

2014

Fluids Barriers CNS

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Cerebral malaria (CM) is a life-threatening complication of falciparum malaria, associated with high mortality rates, as well as neurological impairment in surviving patients. Despite disease severity, the etiology of CM remains elusive. Interestingly, although the Plasmodium parasite is sequestered in cerebral microvessels, it does not enter the brain parenchyma: so how does Plasmodium induce neuronal dysfunction? Several independent research groups have suggested a mechanism in which increased blood–brain barrier (BBB) permeability might allow toxic molecules from the parasite or the host to enter the brain. However, the reported severity of BBB damage in CM is variable depending on the model system, ranging from mild impairment to full BBB breakdown. Moreover, the factors responsible for increased BBB permeability are still unknown. Here we review the prevailing theories on CM pathophysiology and discuss new evidence from animal and human CM models implicating BBB damage. Finally, we will review the newly-described role of matrix metalloproteinases (MMPs) and BBB integrity. MMPs comprise a family of proteolytic enzymes involved in modulating inflammatory response, disrupting tight junctions, and degrading sub-endothelial basal lamina. As such, MMPs represent potential innovative drug targets for CM.

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“…Erythrocytes infected by the P. falciparum E8B strain and free parasites showed significant adherence to confluent human brain microvascular endothelial cells (HBMECs) in an in vitro BBB model (Figure 6). Although in this particular experiment no obvious alteration of tight junctions was observed, other studies performed under different conditions indicated disruption of the BBB induced by the malaria parasite [25]. …”

Section: Cerebral Malaria and Integrity Of The Blood–brain Barriermentioning

confidence: 54%

Possible Roles of Amyloids in Malaria Pathophysiology

et al. 2015

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The main therapeutic and prophylactic tools against malaria have been locked for more than a century in the classical approaches of using drugs targeting metabolic processes of the causing agent, the protist Plasmodium spp., and of designing vaccines against chosen antigens found on the parasite's surface. Given the extraordinary resources exhibited by Plasmodium to escape these traditional strategies, which have not been able to free humankind from the scourge of malaria despite much effort invested in them, new concepts have to be explored in order to advance toward eradication of the disease. In this context, amyloid-forming proteins and peptides found in the proteome of the pathogen should perhaps cease being regarded as mere anomalous molecules. Their likely functionality in the pathophysiology of Plasmodium calls for attention being paid to them as a possible Achilles’ heel of malaria. Here we will give an overview of Plasmodium-encoded amyloid-forming polypeptides as potential therapeutic targets and toxic elements, particularly in relation to cerebral malaria and the blood–brain barrier function. We will also discuss the recent finding that the genome of the parasite contains an astonishingly high proportion of prionogenic domains.

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In vitro study of malaria parasite induced disruption of blood–brain barrier

Cited by 25 publications

References 19 publications

Host response to cytoadherence inPlasmodium falciparum

Host response to cytoadherence inPlasmodium falciparum

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

Possible Roles of Amyloids in Malaria Pathophysiology

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