期刊
ISCIENCE
卷 25, 期 6, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.isci.2022.104407
关键词
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资金
- National Institutes of Health [NIH/NINDS R01NS091616, R01NS125775-01]
- NIH/RCMI [(2U54) MD007602-31]
- NIH/FIC [1K01TW010282, 5R25TW009340]
- NIH/NCATS [TL1TR002382]
- Georgia Clinical and Translational Science Alliance (GCTSA)
Human cerebral malaria is a severe complication of Plasmodium falciparum infection that leads to capillary occlusions, blood-brain barrier rupture, cellular injury, and brain swelling. The parasite-derived HRP2 plays a role in inducing brain injury and inflammation, while the neuroprotective factor NRG1 shows potential as a therapy against HRP2 effects.
Human cerebral malaria (HCM) is a severe complication of Plasmodium falciparum (P.f.) infection that is characterized by capillary occlusions, rupture of the blood-brain barrier (BCC), perivascular cellular injury, and brain swelling. P.f.histidine-rich protein 2 (HRP2), a byproduct of parasitized red blood cell (pRBC) lysis, crosses the BBB when compromised to cause brain injury. We hypothesized that HRP2-induced neuronal damage can be attenuated by Neuregulin-1 (NRG1), an anti. inflammatory neuroprotective factor. Using brain cortical organoids, we determined that HRP2 upre6Alated cell death and inflammatory markers and disorganized brain organoid tissue. We identified toll-like receptors (TLR1 and 2) as potential mediators of HRP2-induced cellular damage and inflamation. Exogenous acute treatment of organoids with P4G1 atte lated effects. The results indicate that HRP2 metes malaria-associated HRP2-induced brain injury and inflammation and that NRG1 may be an effective therapy against HRP2 effects in the brain.
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