Abstract
BackgroundCerebral malaria (CM) is a syndrome characterized by neurological signs, seizures and coma. Despite the fact that CM presents similarities with cerebral stroke, few studies have focused on new supportive therapies for the disease. Hyperbaric oxygen (HBO) therapy has been successfully used in patients with numerous brain disorders such as stroke, migraine and atherosclerosis.Methodology/Principal FindingsC57BL/6 mice infected with Plasmodium berghei ANKA (PbA) were exposed to daily doses of HBO (100% O2, 3.0 ATA, 1–2 h per day) in conditions well-tolerated by humans and animals, before or after parasite establishment. Cumulative survival analyses demonstrated that HBO therapy protected 50% of PbA-infected mice and delayed CM-specific neurological signs when administrated after patent parasitemia. Pressurized oxygen therapy reduced peripheral parasitemia, expression of TNF-α, IFN-γ and IL-10 mRNA levels and percentage of γδ and αβ CD4+ and CD8+ T lymphocytes sequestered in mice brains, thus resulting in a reduction of blood-brain barrier (BBB) dysfunction and hypothermia.Conclusions/SignificanceThe data presented here is the first indication that HBO treatment could be used as supportive therapy, perhaps in association with neuroprotective drugs, to prevent CM clinical outcomes, including death.
Highlights
Cerebral malaria (CM) causes 1–2 million deaths annually; mainly in sub-Saharan African children aged 2–6
We show that in conditions suitable for human use, Hyperbaric oxygen (HBO) therapy prevents CM clinical symptoms in C57BL/6 mice infected with P. berghei ANKA, a model widely used for experimental cerebral malaria (ECM) [31]
Because we observed that HBO had a significant effect on the parasite burden in the infections of Plasmodium berghei ANKA (PbA) and P. berghei NK-65 (PbNK-65), we addressed the question as to whether pressurized oxygen therapy could damage normal red blood cells or inhibit parasite development directly
Summary
Cerebral malaria (CM) causes 1–2 million deaths annually; mainly in sub-Saharan African children aged 2–6. CM is a multi-factorial syndrome characterized by neurological signs, seizures and coma, which can, in turn, lead to death. This syndrome can be associated with a loss of cerebrospinal fluid spaces and ischemia [3], alterations in cerebral blood flow velocity [4], a decrease in cerebral oxygen consumption in CM comatose patients [5] and an increase in the lactate levels of the cerebrospinal fluid [6] which decreases after patients recover consciousness [7]. Recent immunological analyses have shown that, unlike individuals with mild and severe non-cerebral malaria, CM patients present elevated levels of a specific cluster of cytokines, which include TGF-b, TNF-a, IL-1b and IL-10 [16]. Hyperbaric oxygen (HBO) therapy has been successfully used in patients with numerous brain disorders such as stroke, migraine and atherosclerosis
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