Understanding how the brain recovers from cerebral malaria

Cerebral malaria (CM) is one of the most severe complications of malaria, responsible for hundreds of thousands of deaths, each year. At present the only treatment for CM is anti-malarial drugs, which is a non-specific sub-optimal treatment that fails to prevent death in 20% of cases, with 15-30% of survivors of CM also experiencing long-lasting and life-changing neurological sequela. Brain swelling, due to vasogenic oedema, is a key pathological event in CM that, in severe cases, can cause brain stem herniation and death, or cause structural damage in survivors. Thus, there is increasing recognition that the successful recovery from CM depends upon the rate and effectiveness of oedematous fluid removal from the brain. However, the pathways that control vasogenic oedema clearance during the recovery from CM remain unknown. Moreover, the physiologic systems that ultimately cleanse the brain tissue of noxious blood-derived products concomitant with removal of vasogenic oedema to return the brain to immunological homeostasis during resolution of CM have yet to be addressed.

We will subsequently identify how fluid and macromolecule efflux is interconnected with the influx of CSF into the brain tissue during recovery from ECM, and how CSF influx is essential to clean the brain tissue and reestablish brain function and ameliorate neuroinflammation during recovery from ECM. Our results will transform our understanding of how the brain recovers from CM, identifying new therapies for this devastating syndrome.

Project details

Enabling Technologies & Assays

Jul 2021 — Jul 2024

$728,463

United Kingdom