Subscribe to RSS
Alive Animal Model for Epilepsy by Intradorsal Striatum Injection of Colchicine
Background Epilepsy is a neural disorder with repeatable seizure attacks. In this article, we used the neurotoxin colchicine, which is derived from the plant Colchicum autumnale, to introduce a low cost but the more valuable alive animal model for epilepsy.
Materials and Methods Wistar rats weighing 250 to 300 g after intraperitoneal injection of ketamine (100 mg/kg) and xylazine (20 mg/kg) were restrained in the stereotaxic apparatus; they were cannulated in the dorsal striatal area (AP: 0.5 mm; L: 3 mm; V: 3.6 mm). One week later, an injection cannula attached to a 5-µ Hamilton syringe by polyethylene tubing guided 0.05 to 25 μg/rat colchicine in the recovered healthy rats once daily for 4 consecutive days. The control group solely received the saline solution. The behavioral signs of all animals were daily recorded. Finally, the brains of rats under deep euthanasia were collected in 10% formalin and examined histopathologically. The dorsal striatal regions were cut coronally into 3 to 4 µm-thick slices, and then stained with hematoxylin-eosin. They were eventually examined under the light microscope to verify the injection placement or possibility of lesions. All data were analyzed by analysis of variance under α = 0.05.
Results Behaviors were quantified based on Racine five-stage scoring and showed the significant epileptic generalized seizures in alive animal treated by intrastriatal injection of colchicine. However, tissue damage was invisible in the target brain area.
Conclusion The colchicine, using injection successively into the dorsal striatal region of rat, can create recurring epileptic convulsions in the animal.
Article published online:
19 June 2021
© 2021. Indian Epilepsy Society. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
- 1 Kandratavicius L, Balista PA, Lopes-Aguiar C. et al Animal models of epilepsy: use and limitations. Neuropsychiatr Dis Treat 2014; 10: 1693-1705
- 2 Grone BP, Baraban SC. Animal models in epilepsy research: legacies and new directions. Nat Neurosci 2015; 18 (03) 339-343
- 3 Sharma AK, Reams RY, Jordan WH, Miller MA, Thacker HL, Snyder PW. Mesial temporal lobe epilepsy: pathogenesis, induced rodent models and lesions. Toxicol Pathol 2007; 35 (07) 984-999
- 4 White HS. Animal models of epileptogenesis. Neurology 2002; 59 (9, Suppl 5) S7-S14
- 5 Zaniani NR, Karami M, Porkhodadad S. Use of colchicine in cortical area 1 of the hippocampus impairs transmission of non-motivational information by the pyramidal cells. Basic Clin Neurosci 2013; 4 (04) 323-328
- 6 Goldschmidt RB, Steward O. Preferential neurotoxicity of colchicine for granule cells of the dentate gyrus of the adult rat. Proc Natl Acad Sci U S A 1980; 77 (05) 3047-3051
- 7 Daniels M. The role of microtubules in the growth and stabilization of nerve fibers. Ann N Y Acad Sci 1975; 253: 535-544
- 8 Porkhodadad S, Karami M, Jalali Nadoushan MR. Positive effect of nitric oxide on morphine-induced place conditioning in Wistar rats treated by colchicine intra-hippocampal CA1. J Clin Toxicol 2011; 1: 102
- 9 Oakley JC, Harneroff SR, Reynolds AF. Colchicine induced seizures: microtubules and epilepsy. Soc Neurosci Abs 1981; 630
- 10 Sutula T, Goldschmidt R, Steward O. Mechanisms of colchicine neurotoxicity in the dentate gyrus: dissociation of seizures and cell death. Exp Neurol 1983; 81 (03) 683-693
- 11 Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates. Orlando, FL: Academic Press 2007
- 12 Racine RJ. Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol 1972; 32 (03) 281-294
- 13 Kalynchuk LE. Long-term amygdala kindling in rats as a model for the study of interictal emotionality in temporal lobe epilepsy. Neurosci Biobehav Rev 2000; 24 (07) 691-704
- 14 Biziere K, Huguet F, Narcisse G, Breteau M. Affinity of thiocolchicoside and thiocolchicoside analogues for the postsynaptic GABA receptor site. Eur J Pharmacol 1981; 75 (2-3) 167-168
- 15 De PL Riu, Rosati G, Sotgiu S, Sechi G. Epileptic seizures after treatment with thiocolchicoside. Epilepsia 2001; 42 (08) 1084-1086
- 16 Cimino M, Marini P, Cattabeni F. Interaction of thiocolchicoside with [3H]strychnine binding sites in rat spinal cord and brainstem. Eur J Pharmacol 1996; 318 (01) 201-204
- 17 Reynolds AF, Oakley JC. The colchicine experimental epileptic focus: an intracellular study. Brain Res 1984; 322 (02) 326-328
- 18 Deransart C, Lê B-T, Marescaux C, Depaulis A. Role of the subthalamo-nigral input in the control of amygdala-kindled seizures in the rat. Brain Res 1998; 807 (1-2) 78-83
- 19 Biraben A, Semah F, Ribeiro M-J, Douaud G, Remy P, Depaulis A. PET evidence for a role of the basal ganglia in patients with ring chromosome 20 epilepsy. Neurology 2004; 63 (01) 73-77
- 20 Turski L, Cavalheiro EA, Bortolotto ZA, Ikonomidou-Turski C, Kleinrok Z, Turski WA. Dopamine-sensitive anticonvulsant site in the rat striatum. J Neurosci 1988; 8 (11) 4027-4037
- 21 Turski L, Diedrichs S, Klockgether T. et al Paradoxical anticonvulsant activity of the aminobutyrate antagonist bicuculline methiodide in the rat striatum. Synapse 1991; 7 (01) 14-20
- 22 La V Grutta, Amato G, Zagami MT. [The importance of the caudate nucleus in the control of convulsive activity in the amygdaloid complex and the temporal cortex of the cat]. Electroencephalogr Clin Neurophysiol 1971; 31 (01) 57-69
- 23 Ono K, Mori K, Baba H, Wada JA. A role of the striatum in premotor cortical seizure development. Brain Res 1987; 435 (1-2) 84-90
- 24 Vuong J, Devergnas A. The role of the basal ganglia in the control of seizure. J Neural Transm (Vienna) 2018; 125 (03) 531-545
- 25 Aroniadou-Anderjaska V, Fritsch B, Qashu F, Braga MF. Pathology and pathophysiology of the amygdala in epileptogenesis and epilepsy. Epilepsy Res 2008; 78 (2-3) 102-116
- 26 Ravelli RB, Gigant B, Curmi PA. et al Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature 2004; 428 (6979) 198-202
- 27 Maday S, Twelvetrees AE, Moughamian AJ, Holzbaur ELF. Axonal transport: cargo-specific mechanisms of motility and regulation. Neuron 2014; 84 (02) 292-309
- 28 Millecamps S, Julien JP. Axonal transport deficits and neurodegenerative diseases. Nat Rev Neurosci 2013; 14 (03) 161-176
- 29 Lu Y, Chen J, Xiao M, Li W, Miller DD. An overview of tubulin inhibitors that interact with the colchicine binding site. Pharm Res 2012; 29 (11) 2943-2971
- 30 Cela E, Sjöström PJ. Novel optogenetic approaches in epilepsy research. Front Neurosci 2019; Doi: DOI: 10.3389/fnins.2019.00947.
- 31 Goudarzi E, Elahdadi Salmani M, Lashkarbolouki T, Goudarzi I. Hippocampal orexin receptors inactivation reduces PTZ induced seizures of male rats. Pharmacol Biochem Behav 2015; 130: 77-83
- 32 Yang J, Woodhall GL, Jones RS. Tonic facilitation of glutamate release by presynaptic NR2B-containing NMDA receptors is increased in the entorhinal cortex of chronically epileptic rats. J Neurosci 2006; 26 (02) 406-410
- 33 Reddy DS, Kuruba R. Experimental models of status epilepticus and neuronal injury for evaluation of therapeutic interventions. Int J Mol Sci 2013; 14 (09) 18284-18318
- 34 Akdogan I, Adiguzel E, Yilmaz I, Ozdemir MB, Sahiner M, Tufan AC. Penicillin-induced epilepsy model in rats: dose-dependant effect on hippocampal volume and neuron number. Brain Res Bull 2008; 77 (04) 172-177