Mefloquine and Artequin are two effective antimalarial drugs currently in use in the treatment of uncomplicated malaria. This study was to investigate the hippocampal glial degenerative potentials of these drugs in adult Wistar rats. Forty-nine adult Wistar rats weighing 200？g were divided into groups 1–7. Group 1 served as the control that received distilled water, while groups 2–7 received oral doses of 0.86/1.07？mg/kg, 1.71/2.14？mg/kg, and 3.24/4.28？mg/kg of Artequin and 1.07？mg/kg, 2.14？mg/kg, and 4.28？mg/kg of Mefloquine. The treatment lasted for three days, and on day 4 the animals were sacrificed. Their hippocampi were preserved in neutral formal saline and processed by silver impregnation method. The histomorphology of the hippocampal sections of rats in the groups treated with 2.14？mg/kg and 4.28？mg/kg of Mefloquine and 0.86/1.07？mg/kg, 1.71/2.14？mg/kg, and 3.24/4.28？mg/kg of Artequin showed large and dense populations of astrocytes and astrocytes’ processes, with either loss or reduction in the population of oligodendrocytes. There was also loss in the population of pyramidal neurons all compared with the control group. In conclusion, Mefloquine and Artequin administration induced dose-dependent reactive astrocytes and astrocytes’ processes formation in the hippocampus. This may impair the uptake of neurotransmitter and alter neuronal environment thus altering the hippocampal function. 1. Introduction Malaria is one of the tropical diseases caused by the Plasmodium species, falciparum, vivax, and malaria [1]. Despite efforts to control or completely eradicate the disease, malaria continues to be a major cause of human morbidity in the tropics particularly in Southeast Asia and Sub-Saharan Africa with a worldwide prevalence estimated to be in the order of 300–500 clinical cases each year [2]. The treatment of Plasmodium falciparum malaria in Africa is increasingly difficult as resistance to cheap efficient antimalarial drugs such as chloroquine now poses an increasing threat [3]. This is because the emergence of resistance to the malarial parasites is bound to have high impacts on mortality in many African regions [4]. It was as a result of the reported cases of drug resistance that the World Health Organization recommended the introduction of the combination of drugs to replace the single therapeutic drug treatment against Plasmodium falciparum malaria. The use of drug combinations containing the peroxide antimalaria Artemisia which is derived from the herb Artemisia annua was recommended. This combination known as Artemisinin Based
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