After intracerebral injection, some toxic
secreted phospholipases A2 (
sPLA2) can induce epileptic
seizures which bases are currently ill known. We undertook the detailed study of the central neurotoxicity of
paradoxin (PDX), an analog of
taipoxin, in rodents. Since literature strongly suggests a high variability in the
sPLA2 epileptogenic properties, we compared, in an acute model, PDX with
crotoxin (CTX), known to induce
seizures and that may bind to similar neuronal receptors. Related toxic
enzymes (
ammodytoxin A, ATX A, and CTX subunit CB) and the non neurotoxic
sPLA2 from pancreas and PLA2 analog
ammodytin L (AML) were also tested. Despite being highly neurotoxic, PDX did not induce either convulsions or long-lasting seizure fits. The results obtained with the other
enzymes showed that toxic
sPLA2s can effectively be differentiated based on two criteria: the presence of cortically recorded epileptic paroxysmal discharges (E) and convulsions (C). We thus propose to classify the toxic
sPLA2s into different groups depending on their epileptogenic properties: E-C-(PDX), E+C+ (CTX, CB), and E-C+ (ATX A). The non toxic AML and pancreatic
enzyme were E-C-. Moreover, the results obtained with AML, and preliminarily with chemically inhibited CB, suggested that
phospholipid hydrolysis is important to trigger
seizures and convulsions. However, PDX and CTX that possess highly different epileptogenic properties exerted comparable, although slightly different, catalytic activities. Similarly, histological evaluations of the brain of PDX and CTX-treated rats (H&E staining, GFAP immunodetection, hsp70 and c-fos
mRNA detection) did not provide satisfactory clues to explain these large differences. Further studies are strongly required.