TY - JOUR
T1 - Persistent cognitive and motor deficits after successful antimalarial treatment in murine cerebral malaria
AU - Dai, Minxian
AU - Reznik, Sandra E.
AU - Spray, David C.
AU - Weiss, Louis M.
AU - Tanowitz, Herbert B.
AU - Gulinello, Maria
AU - Desruisseaux, Mahalia S.
PY - 2010/12
Y1 - 2010/12
N2 - 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.
AB - 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.
KW - Brain pathology
KW - Chloroquine treatment
KW - Motor coordination
KW - Object recognition
KW - Plasmodium berghei ANKA
KW - Spatial memory
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U2 - 10.1016/j.micinf.2010.08.006
DO - 10.1016/j.micinf.2010.08.006
M3 - Article
C2 - 20800692
AN - SCOPUS:78649902110
SN - 1286-4579
VL - 12
SP - 1198
EP - 1207
JO - Microbes and Infection
JF - Microbes and Infection
IS - 14-15
ER -