Research Projects

Cerebral malaria (CM) is a severe neurological illness affecting children under five years of age in Sub-Saharan African countries. Despite successful anti-malarial treatment, over one-fourth of the children develop severe neurocognitive impairment and epilepsy. Children prone to CM during their neurodevelopmental period suffer from long-term cognitive deficits. Early imaging studies showed increased intracranial pressure and brain swelling, occurring after seizures in children diagnosed with CM. Brainstem signs include posture decerebrate, decorticate and opisthotonic posturing, impaired executive functions language and hearing disability, and motor impairment. Disturbance in one function worsens the other due to various secondary events involved in cognitive functioning. Human post-mortem studies revealed sequestration of infected RBCs in the brain endothelium and endothelial activation as a critical event followed by a sequence of events altering the BBB integrity causing haemorrhages, inadequate oxygen supply to the brain, and edema. The focal rupture of the BBB leads to inflammatory processes inside and around brain capillaries. Crosstalk between multiple pathologic mechanisms intravascular and perivascular changes plays a role in the pathogenesis. One critical transmembrane protein, β-Dystroglycan, a central component of the DGC complex Dystrophin glycoprotein complex, plays a crucial role in central synapses, potentially causing cognitive impairment. It also helps modulate a subgroup of GABAergic inhibitory synapses predominantly present in brain regions with the highest synaptic plasticity. This study aims to advance knowledge on disease pathogenesis using an experimental mice model to decipher the pathological processes underlying human infection. Brain tissue will be homogenized on ice, centrifuged, and layered with sucrose. Electrophysiological recordings will be made from brains removed after decapitation and placed in oxygenated ACSF. Icariin will be administered orally at a concentration of 5 mg/kg, and rescue therapy will be used with second-line therapy drug such as artemether along with Icariin and only artemether.