Hormone limits brain-damage caused by malaria
Research in Africa has found that high levels of a hormone produced in response to anaemia may help protect children from long-term brain damage caused by severe malaria.
An international team led by Dr Climent Casals-Pascual working at the MRC Laboratories in The Gambia and Professor Charles Newton of the KEMRI- Wellcome Trust Programme in Kenya has found that children whose blood contains high levels of the hormone erythropoietin (Epo) recover from cerebral malaria better than those who have less. An artificial version of Epo is a banned substance in athletics as it can boost performance.
When the malaria parasite Plasmodium falciparum moves into the brain, a condition known as cerebral malaria, it becomes even more deadly. Almost one in five children who develop cerebral malaria die. Of those who survive one in ten have neurological problems that cause impaired vision, speech and or movement that are apparent when they leave hospital. Nearly a quarter of surviving children have serious neurological problems and epilepsy when assessed years later.
What prompts the spread of malaria into the brain and how it causes such damage isn’t fully understood. But progress has been made on what influences whether or not a child has long-lasting neurological problems after recovering from cerebral malaria.
‘‘The malaria parasite sticks to brain blood vessels and blocks them. This reduces the oxygen supply to brain tissue and destroys neurones, the brain cells. This is what causes the brain damage associated with cerebral malaria. Epo rescues these cells just before they die,’’ explains Dr Casals-Pascual.
Epo is made by the kidney in response to low oxygen levels in the blood. It encourages multiplication and production of new red blood cells. The molecule is one of a group produced by the body when oxygen levels drop. Epo has been shown to help protect nerve cells in the brain from long-term damage.
The team hypothesised that high levels of Epo could prevent lasting brain damage in children who develop cerebral malaria. To test this idea, they measured how much Epo and VEGF were present in blood and spinal fluid samples from 124 children admitted to hospital with cerebral malaria in Kenya. They then compared the levels from those who developed brain damage with those who didn’t.
They found that a high-level of erythropoietin helps to protect a child against the damage caused when malaria infects the brain but that this protective effect is influenced by age. Children less than two years old with high concentration of erythropoietin were least likely to suffer neurological problems after cerebral malaria.
The results suggest that future treatments based on erythropoietin might help to reduce damage to the brain, Dr Casals-Pascual explains:
“These results are very encouraging and clearly indicate the potential of erythropoietin as a therapy for cerebral malaria. It suggests it could be used as an adjuvant, an agent used in addition to standard therapy to improve outcome. In this context, new erythropoietin derivatives that directly target the brain may be promising candidates to improve the outcome of children with cerebral malaria. However, before we study the efficacy of these molecules to prevent brain damage in children with cerebral malaria, we must study the optimal timing and dosing of Epo to achieve protection. We are also planning to study the protective effect of Epo in other populations where cerebral malaria is an important cause of death. ”
The research was a collaboration between scientists working in Kilifi, Kenya as part of the KEMRI- Wellcome Trust Programme and at the University of Oxford through the National Blood Service at the John Radcliffe Hospital in Oxford.
Original research paper: High levels of erythropoietin are associated with protection against neurological sequelae in African children with cerebral malaria is published online in the Proceedings of the National Academy of Sciences 2008 Feb 8; Electronic publication ahead of print.
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