Premium
Secreted phospholipase A 2 ‐induced neurotoxicity and epileptic seizures after intracerebral administration: An unexplained heterogeneity as emphasized with paradoxin and crotoxin
Author(s) -
Dorandeu Frédéric,
PernotMarino Irmine,
Veyret Josette,
Perrichon Christophe,
Lallement Guy
Publication year - 1998
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19981215)54:6<848::aid-jnr13>3.0.co;2-a
Subject(s) - epilepsy , neurotoxicity , pharmacology , phospholipase a2 , medicine , neuroscience , biology , toxicity , biochemistry , enzyme
After intracerebral injection, some toxic secreted phospholipases A 2 (sPLA 2 ) 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 sPLA 2 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 sPLA 2 from pancreas and PLA 2 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 sPLA 2 s 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 sPLA 2 s 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, hsp 70 and c‐ fos mRNA detection) did not provide satisfactory clues to explain these large differences. Further studies are strongly required. J. Neurosci. Res. 54:848–862, 1998. © 1998 Wiley‐Liss, Inc.