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

Fluids and Barriers of the CNS

Mauro Prato¹  Manuela Polimeni² 

[1] Dipartimento di Scienze della Sanità Pubblica e Pediatriche, Università di Torino, Torino, Italy;Dipartimento di Oncologia, Università di Torino, Torino, Italy

关键词: Inflammation;    Matrix metalloproteinases (MMPs);    Blood–brain barrier (BBB);    Plasmodium;    Cerebral malaria (CM);   

Others  :  806159
DOI  :  10.1186/2045-8118-11-1

 received in 2013-11-25, accepted in 2014-01-24,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Polimeni and Prato; licensee BioMed Central Ltd.

【 图 表 】

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