A Neuropharmacological Analysis of PTZ-Induced Kindling in Mice
Depto. de Farmacologia, Universidade Federal do Rio Grande do Sul, RS, Brazil. General Pharmacology
08/1998; 31(1):47-50. DOI: 10.1016/S0306-3623(97)00423-0
1. Glutamate seems to play a central role in epilepsy, and kindling is considered the most useful experimental model in revealing plastic changes associated with epileptic features. 2. The aim of this study was to optimize pentylenetetrazol (PTZ)-kindling conditions in mice and analyze glutamatergic changes associated with this phenomena. 3. A significant increase (85.7%) in seizuring animals was observed after four PTZ administrations, with all subjects presenting full seizures after five administrations. 4. PTZ kindling, but not acute seizure, significantly increased (169.8%) the specific binding of [3H]glutamate in the cerebral cortex. 5. The development of PTZ-induced kindling in mice was prevented by the coadministration of phenobarbital or diazepam. 6. This study indicates that mice can be used in a reliable model of PTZ-induced kindling and that, as in rats, the kindling increases the specific [3H]glutamate binding in the cerebral cortex, therefore allowing for screening new drugs that can interfere in the plastic changes believed to underlie epileptic phenomena.
Available from: Mohd Makmor-Bakry
- "Electrical kindling usually stimulates a specific brain region, such as amygdala, hippocampus or other brain regions, via chronically implanted depth electrodes (32, 142, 143). Chemical kindling, such as pentylenetetrazoleis ultilized in some studies, but this method has been much less utilized than electrical kindling (144, 145). Pentylenetetrazole kindling involves repeated injection of pentylenetetrazole to cause gradual seizure development as a result of which a significant neuronal loss in hippocampus CA1 and CA3 structures have been observed (144). "
[Show abstract] [Hide abstract]
ABSTRACT: Epilepsy is one of the most common chronic disorders affecting individuals of all ages. A greater understanding of pathogenesis in epilepsy will likely provide the basis fundamental for development of new antiepileptic therapies that aim to prevent the epileptogenesis process or modify the progression of epilepsy in addition to treatment of epilepsy symptomatically. Therefore, several investigations have embarked on advancing knowledge of the mechanism underlying epileptogenesis, understanding in mechanism of pharmacoresistance and discovering antiepileptogenic or disease-modifying therapy. Animal models play a crucial and significant role in providing additional insight into mechanism of epileptogenesis. With the help of these models, epileptogenesis process has been demonstrated to be involved in various molecular and biological pathways or processes. Hence, this article will discuss the known and postulated mechanisms of epileptogenesis and challenges in using the animal models.
Iranian Journal of Basic Medical Science 11/2013; 16(11):1119-1132. · 1.23 Impact Factor
Available from: Daniela Dimer Leffa
- "During the behavioral assessment, the following parameters were registered: latency to the first seizure severity score III, duration of the first seizure severity score III (both in seconds), and the number of seizures. Additionally, convulsive behavior was rated according to the following scale (adapted from Da Silva et al., 1998): 0 = no convulsive behavior; I = jerks of short duration; II = clonic forelimb convulsions lasting less than 3 s; III = clonic forelimb convulsions lasting more than 3 s; IV = generalized convulsions with tonic extension episodes and full status epilepticus; V = death. In the present study, we used in behavioral and biochemical assays only those animals which presented seizures at a severity score rate ≥ III. "
[Show abstract] [Hide abstract]
ABSTRACT: Neuropeptide S (NPS) and its receptor were recently discovered in the central nervous system. In rodents, NPS promotes hyperlocomotion, wakefulness, anxiolysis, anorexia, and analgesia and enhances memory when injected intracerebroventricularly (i.c.v.). Herein, NPS at different doses (0.01, 0.1 and 1nmol) was i.c.v. administered in mice challenged with pentylenetetrazole (PTZ; 60mg/kg) repeatedly injected. Aiming to assess behavioral alterations and oxidative damage to macromolecules in the brain, NPS was injected 5min prior to the last dose of PTZ. The administration of NPS only at 1nmol increased the duration of seizures evoked by PTZ, without modifying frequency and latency of seizures. Biochemical analysis revealed that NPS attenuated PTZ-induced oxidative damage to proteins and lipids in the hippocampus and cerebral cortex. In contrast, the administration of NPS to PTZ-treated mice increased DNA damage in the hippocampus, but not cerebral cortex. In conclusion, this is the first evidence of the potential proconvulsive effects of NPS in mice. The protective effects of NPS against lipid and protein oxidative damage in the mouse hippocampus and cerebral cortex evoked by PTZ-induced seizures are quite unexpected. The present findings were discussed analyzing the paradoxical effects of NPS: facilitation of convulsive behavior and protection against oxidative damage to lipids and proteins.
Pharmacology Biochemistry and Behavior 09/2012; 103(2):197-203. DOI:10.1016/j.pbb.2012.09.001 · 2.78 Impact Factor
Available from: Giovambattista De Sarro
- "The development of chemical kindling induces permanent changes in mouse brain (Ekonomou et al., 2001; da Silva et al., 1998; De Luca et al., 2005). The amino acid level modifications in brain during seizure itself could result from both the kindling process and the physiological shock induced by the seizure. "
[Show abstract] [Hide abstract]
ABSTRACT: Inducible nitric oxide synthase knock-out (iNOS(-/-)) mice are valid models of investigation for the role of iNOS in patho-physiological conditions. There are no available data concerning neuroactive amino acid levels of iNOS(-/-) mice and their behaviour in response to pentylenetetrazole (PTZ). We found no significant differences in the convulsive dose 50 (CD(50)) between iNOS(-/-) and control (iNOS(+/+)) mice, however, iNOS(-/-) mice reach the kindled status more slowly than control, suggesting that in basal condition the GABA-benzodiazepine inhibitory inputs are unaltered by iNOS mutation. Clear differences between iNOS(+/+) and iNOS(-/-) mice amino acid concentrations were evident both in basal conditions and after kindling. Our results show that aspartate was significantly lower in all brain areas studied except the brain stem whereas glutamate and glutamine were significantly higher in the cortex, hippocampus and brain stem. GABA was slightly and not significantly higher in the cortex, hippocampus and brain stem, whereas taurine was significantly higher in all areas except diencephalon and glycine was significantly lower in the diencephalon and cerebellum. In this context, the inability of iNOS(-/-) mice to increase the NO levels following PTZ administrations indicate that NO might play a pro-epileptogenic role in the genesis and development of some types of epilepsy. Since there is no correlation between neurotransmitter levels and the development of kindling, it is possible to exclude that the difference between the two strains is due to an imbalance between the considered neurotransmitters, and it is then possible that this difference is due to the presence of iNOS, which might be involved in long term plasticity of the brain.
Pharmacology Biochemistry and Behavior 01/2007; 85(4):804-12. DOI:10.1016/j.pbb.2006.11.016 · 2.78 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.