Apoptotic changes and aquaporin-1 expression in the choroid plexus of cerebral malaria patients
Charit Srisook1, Supattra Glaharn1, Chuchard Punsawad2
1Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok, 10400, Thailand.
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.
Insights
Cerebral malaria (CM) causes apoptosis in choroid plexus epithelial cells (CPECs), decreasing aquaporin-1 (AQP-1) expression. This may impair cerebrospinal fluid production and brain water balance in CM patients.
Area of Science:
- Neurology
- Pathology
- Cell Biology
Background:
- Cerebral malaria (CM) involves parasitized red blood cell sequestration and is linked to high mortality, often due to cerebral edema.
- Morphological changes in the choroid plexus (CP) and the role of aquaporin-1 (AQP-1) in CM remain understudied.
- Caspase-3 expression, a marker of apoptosis, has not been previously investigated in the context of CM within the CP.
Purpose of the Study:
- To investigate morphological and apoptotic changes in the choroid plexus (CP) of fatal cerebral malaria (CM) patients.
- To evaluate the expression of caspase-3 and aquaporin-1 (AQP-1) in CP epithelial cells (CPECs) of CM patients.
- To explore the potential role of AQP-1 and apoptosis in the pathophysiology of CM.
Main Methods:
- Histopathological evaluation of CP tissue from fatal Plasmodium falciparum malaria patients (16 CM, 5 non-CM [NCM]) and normal controls (NC).
- Immunohistochemistry was employed to detect and quantify caspase-3 and AQP-1 expression in CPECs.
- Statistical analysis was performed to compare expression levels and identify correlations.
Main Results:
- Significant apoptotic changes, including cytoplasmic and nuclear condensation and cell detachment, were observed in CPECs of CM patients compared to NCM and NC groups (p < 0.05).
- Apoptotic changes in CPECs positively correlated with increased nuclear caspase-3 expression.
- AQP-1 expression in CPECs was significantly reduced in CM patients compared to NCM and NC groups (p < 0.001), with a negative correlation between caspase-3 and AQP-1 expression (r=-0.450, p=0.024).
Conclusions:
- Apoptotic alterations in CPECs, indicated by increased caspase-3 expression, are a feature of cerebral malaria.
- Reduced AQP-1 expression in CPECs of CM patients suggests impaired water transport function.
- CPEC dysfunction due to apoptosis and altered AQP-1 may contribute to reduced cerebrospinal fluid production and disrupted water homeostasis in the brain during CM.
