Persistent cognitive and motor deficits after successful antimalarial treatment in murine cerebral malaria.
Human cerebral malaria causes neurological and behavioral deficits which persist long after resolution of infection and clearance of parasites with antimalarial drugs. Previously, we demonstrated that during active infection, mice with cerebral malaria demonstrated negative behavioral outcomes. Here we used a chloroquine treatment model of cerebral malaria to determine whether these abnormal outcomes would be persistent in the mouse model. C57BL/6 mice were infected with Plasmodium berghei ANKA, and treated for ten days. After cessation of chloroquine, a comprehensive assessment of cognitive and motor function demonstrated persistence of abnormal behavioral outcomes, 10 days after successful eradication of parasites. Furthermore, these deficits were still evident forty days after cessation of chloroquine, indicating persistence long after successful treatment, a hallmark feature of human cerebral malaria. Thus, cognitive tests similar to those used in these mouse studies could facilitate the development of adjunctive therapies that can ameliorate adverse neurological outcomes in human cerebral malaria.
Dai
Minxian
M
Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St Johns University, Queens, NY 11439, USA.
Reznik
Sandra E
SE
Spray
David C
DC
Weiss
Louis M
LM
Tanowitz
Herbert B
HB
Gulinello
Maria
M
Desruisseaux
Mahalia S
MS
D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage*; D002738:Chloroquine / Q000008:administration & dosage; D003072:Cognition Disorders / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D016779:Malaria, Cerebral / Q000150:complications* / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D016472:Motor Neuron Disease / Q000503:physiopathology*; D010962:Plasmodium berghei / Q000472:pathogenicity*
D000962:Antimalarials; D002738:Chloroquine
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