Glial activation and matrix metalloproteinase release in cerebral malaria.
Although neurological symptoms associated with cerebral malaria (CM) are largely reversible, recent studies suggest that lasting neurological sequelae can occur. This may be especially true for children, in whom persistent deficits include problems with memory and attention. Because the malaria parasite is not thought to enter the brain parenchyma, lasting deficits are likely related to factors including the host response to disease. Studies with a rodent model, and with human postmortem tissue, suggest that glial activation occurs with CM. In this review, the authors will highlight studies focused on such activation in CM. Likely causes will be discussed, which include ischemia and activation of blood brain barrier endothelial cells. The potential consequences of glial activation will also be discussed, highlighting the possibility that glial-derived proteinases contribute to structural damage of the central nervous system (CNS). Of note, for the purposes of this focused review, glial activation will refer to the activation of astrocytes and microglial cells; discussion of oligodendroglial cells will not be included. In addition, although events thought to be critical to the pathogenesis of CM and glial activation will be covered, a comprehensive review of cerebral malaria will not be presented. Excellent reviews are already available, including Coltel et al (2004; Curr Neurovasc Res 1: 91-110), Medana and Turner (2006; Int J Parasitol 36: 555-568), and Hunt et al (2006; Int J Parasitol 36: 569-582).
Szklarczyk
A
A
Departments of Neurology, Johns Hopkins University, Baltimore, Maryland 21287, USA.
Stins
M
M
Milward
E A
EA
Ryu
H
H
Fitzsimmons
C
C
Sullivan
D
D
Conant
K
K
D000818:Animals; D002490:Central Nervous System / Q000276:immunology* / Q000473:pathology; D002494:Central Nervous System Infections / Q000134:cerebrospinal fluid* / Q000503:physiopathology; D004789:Enzyme Activation; D006801:Humans; D016779:Malaria, Cerebral / Q000201:enzymology* / Q000276:immunology / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000134:cerebrospinal fluid; D017628:Microglia / Q000166:cytology / Q000502:physiology*
D020780:Matrix Metalloproteinase 9