神经系统疾病

Investigation of an Optimized Protocol for Brucine-Induced Seizure Model

Abstract

Xinxin Fan, Tinglei Li, Jinmei Li, Yingying Li and Dan Chen

Object: Strychnine has been reported to develop seizure models. As its analogue, brucine may also have such property. The aim of the study was to create a chemoconvulsant model of seizures by fractionated administration of brucine.

Methods: Healthy male Sprague-Dawley rats (n=140) were allocated randomly into three groups: experimental group， normal saline control group and alcohol control group. Rats in experimental group were then randomly divided into six groups during the kindling process: three of the six subgroups were single-dose subgroups, while another three were fractionated-dose subgroups. Rats from three single-dose subgroups (n=20 for each subgroup) received single injection of brucine at three various dose levels (91 mg/kg, 100 mg/kg and 110 mg/kg, respectively); rats from the other three fractionated-dose subgroups (n=20 for each subgroup) received fractionated injections of brucine by three times with one third of the total dose each time. Rats from normal saline and alcohol control group were given normal saline and solvent injection (n=10 for each group). Seizure frequency and intensity (rated as stage 1-5 according to Racine scale), duration and electroencephalographic activity were recorded. Seizures were observed in all single-dose and fractionated-dose subgroups.

Results: As dose increased, higher frequency and intensity of seizures were observed. At the dose of 110mg/kg, all rats died after stage 5 seizures in both single and fractionated dose subgroups. At doses of 91mg/kg and 100mg/kg，in single-dose subgroups, 75.00-95.00% rats were observed stage 5 seizures, but the mortality was 75.00%-95.00%; In fractionated-dose subgroups, 50.00%-100.00% rats were observed stage 5 seizures, while the mortality was 0.00%-30.00%.

Conclusion: The study has provided a novel chemoconvulsant model of seizures induced by brucine, and established an appropriate method to develop the model that had not been found in previous literature review.