Brain cells can detect the presence of malaria parasites in the blood, according to researchers from the Instituto Gulbenkian de Ciência (IGC). They claimed that endothelial cells in the brain play a crucial part in early malaria parasite infection detection, as stated in their study, which was published in Proceedings of the National Academy of Sciences

Malaria Parasite Connecting to Human Red Blood Cell
(Photo: NIAID/Wikimedia Commons)
Malaria Parasite Connecting to Human Red Blood Cell


What is Cerebral Malaria?

The severe type of P. falciparum malaria that results in brain symptoms is referred to as cerebral malaria by the World Health Organization (WHO). Patients with cerebral malaria frequently go into a coma after a seizure that lasts longer than 30 minutes. This may be the case, but patients should still be treated for severe malaria if they exhibit any level of altered awareness or other symptoms of brain dysfunction.

According to News Medical Sciences, cerebral malaria is a severe neurological consequence of Plasmodium falciparum infection that affects 1% of children under five. According to WHO, there were an estimated 241 million cases of malaria worldwide in 2020,

Endothelial cells and interferon-β 

Endothelial cells, specialized cells from the inner lining of blood vessels, construct a barrier between the blood and the brain to stop specific substances and cells from entering. However, when an uncontrolled inflammatory response to infection happens, considerable changes in this barrier lead to cerebral malaria. 

In recent years, experts in this field have focused on a chemical called interferon-β that appears to be connected to this degenerative process. This extremely inflammatory chemical has two opposing functions. It can either protect tissues or destroy them. For instance, certain concentrations and infection stages might lead to lung injury. Cerebral malaria is hypothesized to have a similar dynamic.

Researchers employed mice that simulate various malaria symptoms in humans and a genetic engineering approach that allowed them to remove this sensor in several cell types to come to these conclusions. They concluded that the animal's symptoms were less severe and that the infection caused fewer deaths when they eliminated this sensor in brain endothelial cells. At that point, they understood how significantly these brain cells contributed to the pathophysiology of cerebral malaria.

Cerebral Malaria Dynamic

The researchers asserted that they believed brain endothelial cells functioned later. However, as a result of their experiments, they eventually realized that the brain cells were participants from the start. Teresa Pais, a post-doctoral researcher at the IGC and the study's first author, provided this explanation.

According to Pais, immune system cells are typically associated with this initial stage of the response to an infection.  However, because they have the same sensors, brain cells and possibly other organs can detect infections.

But they were taken aback by the factor, a consequence of the parasite's action, that turned on the sensor and started the cell reaction. According to scientists, the parasite multiplies after entering the bloodstream and invading the host's red blood cells. Then it digests hemoglobin to obtain nutrition.

A chemical known as heme is created during this process, and endothelial cells can carry it in the blood in the form of minute particles. Heme serves as an alert for the immune system when this occurs. The researcher said that they weren't expecting heme to enter cells in this manner and initiate this reaction involving interferon-β in endothelial cells.

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Future Study to Prevent Cerebral Malaria 

According to Carlos Penha Gonçalves, the group's chief investigator, the next step will be to attempt to suppress the function of this sensor inside the endothelial cells to ascertain whether it may influence the host's reaction and halt brain pathology in its early stages.

He said that if they could utilize inhibitors of the sensor in tandem with antiparasitic medications, perhaps they could stop the loss of neural function and avoid sequelae, which are a significant issue for children who survive cerebral malaria.

 

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