Theses

Date of Award

2026

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biological Sciences

First Advisor

Dr. Julio Gallego-Delgado

Abstract

Malaria is a tropical parasitic disease transmitted by female Anopheles spp. mosquitos. The most severe neurological complication of malaria is cerebral malaria (CM), caused by Plasmodium falciparum infection. During CM there is a blockage of small blood vessels in the brain caused by the sequestration of P.falciparum infected red blood cells, along with the accumulation of perivascular monocytes, triggering an excessive release of pro-inflammatory cytokines. The cytokine Macrophage migration inhibitory factor (MIF) binds to the CD74 receptor, initiating intracellular signaling, triggering pro-inflammatory pathways. The renin-angiotensin system is a primary regulator of blood volume, electrolyte homeostasis, and is involved in vascular permeability, with Angiotensin II playing a key role. When angiotensin II binds to the angiotensin II type 1 receptor (AT1), it promotes pro-inflammatory effects leading to neurodegeneration. However, when bound to the angiotensin II type 2 receptor (AT2), it promotes anti-inflammatory effects, leading to neuroprotection. It has been demonstrated that blocking the AT1 receptor, and stimulating the AT2 receptor, displays a neuroprotective effect in neurological disorders. This study puts the spotlight on the MIF/CD74 pathway as a potential contributor to cerebral malaria–associated neuroinflammation and suggest mechanistic parallels with other neuroinflammatory disorders, and test whether regulation of the renin-angiotensin system may affect neuroinflammatory signaling during CM.

Available for download on Thursday, March 23, 2028

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