Antioxidants can prevent cerebral malaria in Plasmodium berghei-infected mice

A/J and CBA/H mice infected with Plasmodium berghei ANKA, a murine model of cerebral malaria, were used to see whether antioxidants influenced the outcome of this disease. Untreated, infected mice died 7 to 9 days after infection, often with cerebral symptoms. Haemorrhages, mononuclear infiltration and oedema were present in the central nervous system (CNS). Feeding a diet containing 0.75% (w/w) butylated hydroxyanisole (BHA) greatly altered the course of this disease. Death was delayed by up to 2 weeks and mice appeared healthy at parasitaemias that would have caused cerebral symptoms and death had they been on a conventional diet. BHA-fed mice showed few or no cerebral symptoms at a time at which control mice were clearly affected, and greatly reduced haemorrhages, mononuclear infiltration and oedema when the CNS was examined. Similar, but more consistent, protective effects were seen after administration of BHA by repeated injections or in osmotic pumps. The combination of superoxide dismutase and catalase, coupled to polyethylene glycol, when administered intravenously also protected mice against death from cerebral complications. Permeability of the blood-brain barrier was monitored by the use of 125I-labelled bovine serum albumin, 51Cr-labelled erythrocytes and the dye Evans blue, all of which are normally excluded from the CNS. Infected mice on control diet showed an increase in Evans blue staining and 125I and 51Cr retention in the CNS tissue itself. Feeding the diet containing BHA reduced these indices of increased blood-brain barrier permeability. In view of the potent radical scavenging activity of BHA in many other systems it is likely, but unproven, that this is its main role here. The protective effect of superoxide dismutase and catalase lends support to the idea that reactive oxygen species are involved in the pathology of experimental cerebral malaria.