Secretory phospholipase A(2) potentiates glutamate-induced rat striatal neuronal cell death in vivo

The secretory phospholipases A(2) (sPLA(2)) OS2 (10, 20 and 50 pmol) or OS1 , (50 pmol) purified from taipan snake Oxyuranus scutellatus scutellatus ve nom, and the excitatory amino acid glutamate (Glu) (2.5 and 5.0 mu mol) wer e injected into the right striatum of male Wistar rats. Injection of 10 and 20 pmol OS2 caused no neurological abnormalities or tissue damage. OS2 (50 pmol) caused apathy and circling towards the injection side. Histology rev ealed an infarct at the injection site. Injection of 50 pmol OS1 showed ver y little or no signs of neurotoxicity. Injection of 2.5 mu mol Glu caused n o tissue damage or neurological abnormality. After injection of 5.0 mu mol Glu, the animals initially circled towards the side of injection, and gradu ally developed generalized clonic convulsions. These animals showed a well demarcated striatal infarct. When non-toxic concentrations of 20 pmol OS2 a nd 2.5 mu mol Glu were co-injected, a synergistic neurotoxicity was observe d. Extensive histological damage occurred in the entire right hemisphere, a nd in several rats comprising part of the contralateral hemisphere. These a nimals were apathetic in the immediate hours following injection, with circ ling towards the side of injection in the following days. Thus, OS2 greatly potentiates glutamate excitoxicity in vivo. (C) 1999 Elsevier Science Irel and Ltd. All rights reserved.