Cerebrospinal Fluid Cytokine Levels and Cognitive Impairment in Cerebral Malaria
Chandy C. John,Angela Panoskaltsis-Mortari,Robert O. Opoka,Gregory S. Park,Paul J. Orchard,Anne M. Jurek,Richard Idro,Justus Byarugaba,Michael J. Boivin +8 more
TLDR
Elevated cerebrospinal fluid but not serum TNF-alpha levels on admission were associated with an increased risk of neurologic deficits 3 months later and correlated negatively with age-adjusted scores for attention, working memory, and working memory 6 months later.Abstract:
Cerebrospinal fluid (CSF) and serum levels of 12 cytokines or chemokines important in central nervous system (CNS) infections were measured in 76 Ugandan children with cerebral malaria (CM) and 8 control children. As compared with control children, children with cerebral malaria had higher cerebrospinal fluid levels of interleukin (IL)-6, CXCL-8/IL-8, granulocyte-colony stimulating factor (G-CSF), tumor necrosis factor-alpha (TNF-alpha), and IL-1 receptor antagonist. There was no correlation between cerebrospinal and serum cytokine levels for any cytokine except G-CSF. Elevated cerebrospinal fluid but not serum TNF-alpha levels on admission were associated with an increased risk of neurologic deficits 3 months later (odds ratio 1.55, 95% CI: 1.10, 2.18, P = 0.01) and correlated negatively with age-adjusted scores for attention (Spearman rho, -0.34, P = 0.04) and working memory (Spearman rho, -0.32, P = 0.06) 6 months later. In children with cerebral malaria, central nervous system TNF-alpha production is associated with subsequent neurologic and cognitive morbidity.read more
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Cerebral Malaria: Mechanisms of Brain Injury and Strategies for Improved Neurocognitive Outcome
Richard Idro,Kevin Marsh,Kevin Marsh,Chandy C. John,Charles R. Newton,Charles R. Newton,Charles R. Newton +6 more
TL;DR: Possible mechanisms of brain injury in cerebral malaria are examined, relating this to the pathogenesis of the disease, and prospects for improved neurocognitive outcome are explored.
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Cerebral malaria in children is associated with long-term cognitive impairment
Chandy C. John,Paul Bangirana,Justus Byarugaba,Robert O. Opoka,Richard Idro,Anne M. Jurek,Baolin Wu,Michael J. Boivin +7 more
TL;DR: Cerebral malaria is associated with long-term cognitive impairments in 1 of 4 child survivors and future studies should investigate the mechanisms involved so as to develop interventions aimed at prevention and rehabilitation.
Journal ArticleDOI
The roles of TNF in brain dysfunction and disease.
TL;DR: This review summarizes the burgeoning literature on cytokines, and how the functions of these molecules, particularly TNF, are influencing the outlook of researchers on the pathophysiology of these diseases, including Alzheimer's disease and other encephalopathies.
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Cerebral malaria: why experimental murine models are required to understand the pathogenesis of disease.
TL;DR: The current understanding of the parasitological and immunological events leading to human and experimental cerebral malaria is reviewed, and why it is believed that studies with experimental models of CM are crucial to define the pathogenesis of the condition.
Journal ArticleDOI
Neuroinflammation and synaptic plasticity: theoretical basis for a novel, immune-centred, therapeutic approach to neurological disorders
TL;DR: It is proposed that a more accurate characterization of the mechanisms underlying the immune-mediated control of synaptic plasticity could represent the basis for the development of a novel immune-centred therapeutic approach to neurological disorders.
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