Abstract
Cerebral malaria is characterized by permanent cognitive impairments in Plasmodium-infected children. Antimalarial therapies show little effectiveness to avoid neurological deficits and brain tissue alterations elicited by severe malaria. Melatonin is a well-recognized endogenous hormone involved in the control of brain functions and maintenance of blood–brain barrier integrity. The current study has evaluated the effect of melatonin on the histological alterations, blood–brain barrier leakage, and neurocognitive impairments in mice developing cerebral malaria. Swiss mice infected with Plasmodium berghei ANKA strain was used as cerebral malaria model. Melatonin treatment (5 and 10 mg/kg) was performed for four consecutive days after the infection, and data have shown an increased survival rate in infected mice treated with melatonin. It was also observed that melatonin treatment blocked brain edema and prevented the breakdown of blood–brain barrier induced by the Plasmodium infection. Furthermore, hematoxylin and eosin staining revealed that melatonin mitigates the histological alterations in Plasmodium-infected animals. Melatonin was also able to prevent motor and cognitive impairments in infected mice. Taken together, these results show for the first time that melatonin treatment prevents histological brain damages and neurocognitive alterations induced by cerebral malaria.
Highlights
Malaria is a potentially life-threatening disease affecting an estimated 207 million people each year (WHO, 2017)
Eighty percent of Plasmodium berghei ANKA (PbA)-infected mice succumbed to cerebral malaria (CM) on days 8–11 whereas 20% died on day 15 due to severe malaria (Figure 1A)
At 11 days post-infection, the melatonintreated group exhibited a 57% of survival rate with mice showing no CM neurological symptoms when compared to the PbAinfected group that exhibited a 16% survival rate (Figure 1A)
Summary
Malaria is a potentially life-threatening disease affecting an estimated 207 million people each year (WHO, 2017). Majority of the fatal cases were due to cerebral malaria (CM), which is the most severe neurological complication of Plasmodium falciparum infection that affects mainly children under 5 years of age (WHO, 2000; Idro et al, 2005). Major clinical symptoms of CM include dyspnea, fever, sudden bleeding, disorientation, convulsions, coma, and death. Melatonin Protects Brain From Cerebral Malaria exhibit long-term neurocognitive impairments such as cortical blindness, hearing loss, ataxia, and memory and attention disorders, which is partly due to the fact that antimalarial drugs do not prevent the damages in the central nervous system (CNS) parenchyma (John et al, 2008; Rénia et al, 2012). The mechanism of CM-induced brain injuries is still not fully understood. Data from literature describe the role of proinflammatory cytokines, microglial activation, and oxidative stress on the pathogenicity of CM (Hunt and Grau, 2003)
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