T h e role o f T -cells in developm ent of experim ental cerebral m alaria w as analysed in C 5 7 B 1 /6 J a n d C 5 7 B l/1 0 m ic e in fected w ith Plasm odium berghei K173 or Plasmodium berghei A N K A b y tre a tm e n t w ith a n ti-C D 4 o r a n ti-C D 8 m A b s. M ic e w ere p ro tected against cerebral m alaria (C M ) w hen a n ti-C D 4 or a n ti-C D 8 m A b s w e re in je c te d b e fo re o r d u rin g in fectio n . E v e n in m ice in en d -stag e disease, i.e. w ith a body te m p e ra tu re below 35-5 °C, tre a tm e n t w ith a n ti-C D 4 o r a n ti-C D 8 a n tib o d ies or th e com bination protected against CM , w h ereas ch lo ro q u in e tre a tm e n t w as c o m p le te ly ineffective in in h ib itin g f u r th e r developm ent of th e cerebral syndrom e.

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Experimental cerebral malaria (ECM) can be induced in C57Bl mice by infection with Plasmodium berghei K173 parasites. Behavioral changes shortly before they die of ECM may reflect disturbance of the integrity of the blood-brain barrier (BBB). Folic acid elicits strong convulsive activity if the permeability of the BBB is increased. Administration of folic acid to mice during development of ECM induced convulsions. Interventions known to prevent fatal outcome from ECM, such as splenectomy or treatment with anti-CD4 or anti-CD8 monoclonal antibodies, also prevented sensitivity to folic acid -induced convulsions. In addition, infected mice with ECM and sensitive to folic acid -induced convulsions, recovered from this sensitivity after treatment with anti -T cell antibodies within 4 h. These data suggest that disturbance of the permeability of the BBB can be reversed and depends on the involvement of T cells.C57Bl mice infected with Plasmodium berghei K173 paraepileptic activity by folic acid treatment if the permeability of the BBB was increased was applied in our model of ECM. sites die of experimental cerebral malaria (ECM) [1]. Mice that develop ECM exhibit behavioral changes during the last 24 hIn this study, we assessed the effect of folic acid treatment on mice with ECM and of interventions by splenectomy with of life that reflect convulsive activity [2]. In this model, ECM is associated with leukocyte adherence to the microvascular anti-CD4 and anti-CD8 monoclonal antibodies (MAbs). endothelium, edema, and petechiae in the brain [3,4] . Using Evans blue or Monastral blue as indicators of the integrity of Materials and Methods the blood-brain barrier (BBB), Thumwood et al. [5] and NeillMice. Female C57Bl/6J mice, ages 6-10 weeks, were oband colleagues [6,7] reported increased vascular permeability tained from specific pathogen-free colonies maintained at the Cenin mice that developed ECM (P. berghei ANKA -infected CBA Convulsions are common in childhood malaria and are assoKretschmar, Tübingen, Germany) has been maintained by weekly ciated with severity of disease and mortality [8]. Recent obsertransfer of parasitized erythrocytes (PE) from infected into naive vations show that childhood convulsions are particularly assomice for ú30 years. Experimental mice were infected intraperitociated with malaria, but not necessarily in combination with neally (ip) with 10 3 PE from blood of infected donors. Parasitemia. Thin blood films were made from tail blood fever, suggesting that Plasmodium falciparum parasites have stained with May-Grünwald and Giemsa solutions, and the proporepileptogenic properties [9]. Sequestration and adherence of P.tion of parasitized red blood cells was determined. falciparum -infected erythrocytes in the cerebral vasculature Detection of ECM. ECM was detected as described by Curfs[10] may disturb the permeability of the BBB [11, 12]