Avaliação dos níveis extracelulares de GABA e glutamato no sistema nervoso central de camundongos infectados com Plasmodium berghuei ANKA

Abstract

Cerebral malaria (CM) caused by Plasmodium falciparum results in high mortality, especially in children under 5, with up to 25% of survivors experiencing neurological sequelae such as cognitive impairment and seizures. The neurochemical mechanisms behind these impairments are not well understood. This study aimed to characterize changes in the levels of the neurotransmitters glutamate (GLU) and γ-Aminobutyric acid (GABA) in the central nervous system (CNS) during experimental cerebral malaria (ECM). ECM was induced in Swiss mice with Plasmodium berghei ANKA (PbA), and the animals were monitored for parasitemia, survival, and neurological impairments using the Rapid Murine Coma and Behavior Scale (RMCBS). On the 7th day post-infection (d.p.i), blood-brain barrier (BBB) disruption was assessed using Evans Blue dye, and glial cell evaluation was performed by immunofluorescence. Results showed that PbA-infected mice began to succumb to CM by the 6th d.p.i, with 100% mortality by the 10th d.p.i. Behavioral impairments were observed from the early stages of infection. Significant BBB permeability changes and increased expression of glial activation markers were noted in infected mice. There was a marked increase in GLU levels in the brain and cerebellum on days 3, 5, and 7 post-infection. GABA levels increased on days 3 and 5, returning to control levels by day 7. These findings indicate significant neurochemical alterations in GABAergic and glutamatergic neurotransmission, accompanied by neurological and vascular impairments, suggesting their involvement in the development of neurological symptoms in CM.