TsTx toxin isolated from Tityus serrulatus scorpion venom induces spontaneous recurrent seizures and mossy fiber sprouting

Abstract

Purpose: To characterize the long-term behavioral, electroencephalographic (EEG) and histopathologic features after a single TsTx microinjection into the hippocampus of rats. Method: TsTx, 2 μg, or 1 μl of 0.1 M phosphate buffer was injected into the right dorsal hippocampus of the rat. EEG records and behavioral observations were made over a period of 10 h after injection. For a period of 4 months, the animals were observed for the occurrence of convulsive seizures. At the end of the experiment, the brains were processed by the neo-Timm and Nissi methods. Results: After intrahippocampal TsTx injection, three distinct phases were observed: (a) an immediate period that lasted 1 day, during which the motor and electrographic seizures characteristic of status epilepticus (SE) were seen; (b) a silent period (31-49 days), characterized by normal EEG and behavior; and (c) a period of spontaneous recurrent seizures (SRSs). The seizure frequency was one to two per week. Four months after TsTx injection, hippocampal neuronal loss and mossy fiber sprouting in the supragranular layer of the dentate gyrus were observed. Conclusions: The SRSs observed in this study may be associated with the TsTx-induced SE and brain damage. All animals injected with the toxin showed massive pyramidal neuronal loss in the dorsal hippocampus as well as intense gliosis and atrophy. Mossy fiber sprouting in the supragranular layer of the dentate gyrus was observed in those animals that had SRSs. The effects observed may be due, at least in part, to TsTx-enhanced release of glutamate in hippocampal pathways.