Diazepam and pentobarbital protect against scorpion venom toxin-induced epilepsy.
We have characterized earlier the long-term behavioural, electroencephalographic and histopatologic features after a single TsTx microinjection, consisting of a neuropeptide isolated from the Tityus serrulatus scorpion venom, into the hippocampus of rats. TsTx was able to induce status epilepticus (SE) and developed later epilepsy. The present study was designed to investigate the outcomes of diazepam plus pentobarbital administered at 30 min, 1, 2 or 6h after the beginning of TsTx-induced SE, on the development of spontaneous recurrent motor seizures (SRMSs), mossy fibre sprouting and hippocampal neurodegeneration in rats. The administration of diazepam (DZ)+pentobarbital (PB) 30 min after the beginning of the TsTx-induced SE was able to markedly reduce the frequency of the SRMSs and prevent the development of mossy fibres sprouting and hippocampal lesion. In the other groups the augment of the extent of hipocampal neurodegeneration, the frequency of SRMSs and degree of aberrant mossy fibre sprouting was directly proportional to the time that the animals were subjected to TsTx-induced SE. In conclusion, our results point out that the early blockade of the TsTx-induced SE with diazepam plus pentobarbital, was effective treatment against later epilepsy development. The effectiveness of this treatment depends on the time that the animals were subjected to the SE. Furthermore, the TsTx model could be a useful tool to study antiepileptogenic drugs in chronic epileptic animals, neuronal degeneration, as well as for the mechanisms underlying epilepsy.
Luongo
Roberta
R
Laboratory of Pharmacology, Butantan Institute, Av. Dr. Vital Brasil, 1500, São Paulo, SP 05503 900, Brazil. roberta rl@hotmail.com
Oliveira
Diana Amaral
DA
Lebrun
Ivo
I
Sandoval
Maria Regina Lopes
MR
D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage*; D002452:Cell Count; D016923:Cell Death; D003975:Diazepam / Q000008:administration & dosage*; D004569:Electroencephalography; D004827:Epilepsy / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000473:pathology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010424:Pentobarbital / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012604:Scorpion Venoms / Q000633:toxicity*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology
D000927:Anticonvulsants; D018696:Neuroprotective Agents; D012604:Scorpion Venoms; D010424:Pentobarbital; D003975:Diazepam