Apoptotic changes and aquaporin-1 expression in the choroid plexus of cerebral malaria patients

Abstract

Background Cerebral malaria (CM) is associated with sequestration of parasitized red blood cells (PRBCs) in the capillaries. Often, the association of CM with cerebral oedema is related with high mortality rate. Morphological changes of the choroid plexus (CP) and caspase-3 expression in CM have not been reported. In addition, limited knowledge is known regarding the role of aquaporin (AQP)-1 in CM. The present study evaluated changes in the CP, explored apoptotic changes and AQP-1 expression in CP epithelial cells (CPECs) in fatal CM patients. Methods CP from fatal Plasmodium falciparum malaria patients (5 non-CM [NCM], 16 CM) were retrieved and prepared for histopathological evaluation. Caspase-3 and AQP-1 expressions in CPECs were investigated by immunohistochemistry. Results Histologically, apoptotic changes in CPECs were significantly observed in the CM group compared with the NCM and normal control (NC) groups (p < 0.05). These changes included cytoplasmic and nuclear condensation/shrinkage of CPECs and detachment of CPECs from the basement membrane. The apoptotic changes were positively correlated with caspase-3 expression in the nuclei of CPECs. In addition, AQP-1 expression in CPECs was significantly decreased in the CM group compared with the NCM and NC groups (all p < 0.001). A negative correlation (rs = − 0.450, p = 0.024) was documented between caspase-3 expression in the nuclei of CPECs and AQP-1. Conclusions Apoptotic changes and altered AQP-1 expression may contribute to CPEC dysfunction and subsequently reduce cerebrospinal fluid production, affecting the water homeostasis in the brains of patients with CM.

The Role of Aquaporins in Epileptogenesis—A Systematic Review

“…Moreover, modified AQP1 expression may determine choroid plexus epithelial cell disfunction, leading to alterations in cerebrospinal fluid production and thus affecting the water homeostasis. Interestingly, in their study, Srisook and colleagues demonstrated the role of cerebral malaria (CM) in inducing apoptotic changes to choroid plexus epithelial cells, to define AQP1 as a potential target to reduce brain edema associated with CM [8]. On the other hand, AQP9 represents the only aquaglyceroprotein in the brain.…”