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Epilepsy
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Donald C. Barr, Andres M. Kanner
The pathophysiology of human epilepsy is very complex and is not completely understood. Experimental studies in animal models of epilepsy have elucidated a variety of potential pathophysiologic mechanisms of the epileptogenic process. For example, kindling, is a process by which repeated subthreshold electrical stimulation of specific neuroanatomical structures (e.g. amygdala) lead to the development of focal electrographic followed by electroclinical seizures, which over time worsen in severity to the equivalent of generalized seizures. The kindling model has been used to study epileptogenesis in focal epilepsy (e.g. posttraumatic epilepsy and focal epilepsy associated with mesial temporal sclerosis).42 In this model, following a causative event (e.g. significant head trauma), there may be a latent period (and sometimes a second “hit”) before the clinical development of seizures.
Absence seizures in the GAERS model: subthalamic nucleus stimulation
Published in Hans O Lüders, Deep Brain Stimulation and Epilepsy, 2020
Alim-Louis Benabid, Laurent Vercueil, Karine Bressand, Maurice Dematteis, Abdelhamid Benazzouz, Lorella Minotti, Philippe Kahane
Only selected animal models of epilepsy emulate human epilepsy. These include status epilepticus injury causing partial-onset epilepsy, several genetic epilepsy models of generalized epilepsy, and models of cortical dysgenesis. Many human disorders associated with seizures do not have animal models.
Pharmacokinetic/Pharmacodynamic Correlations of Anticonvulsants
Published in Hartmut Derendorf, Günther Hochhaus, Handbook of Pharmacokinetic/Pharmacodynamic Correlation, 2019
Meindert Danhof, Rob A. Voskuyl
Over the years several animal models of epilepsy have been developed.9–12 In these models epileptiform phenomena can occur spontaneously (genetic models of epilepsy) or as the result of the application of an external stimulus (e.g., electrical stimulation or the administration of a convulsive agent like pentylenetetrazol). In addition a further differentiation can be made between (1) models based on the development of maximal seizures, which consist of a characteristic pattern of tonic flexion and extension followed by clonic activity (e.g., the maximal electroshock model); (2) models using threshold seizures, which are characterized by the occurrence of a short period of clonic activity only (e.g., the subcutaneous pentylenetetrazol test); and (3) models based on kindling, which emphasize the developmental aspects of epilepsy.
The 5-HT7 receptor antagonist SB-269970 alleviates seizure activity and downregulates hippocampal c-Fos expression in pentylenetetrazole-induced kindled rats
Published in Neurological Research, 2022
Bilal Sahin, Ercan Ozdemir, Erkan Gumus, Mustafa Ergul, Ahmet Sevki Taskiran
Animal models of epilepsy and epileptic seizures are crucial to understanding the basic mechanisms involved in epileptogenesis. Pentylenetetrazole (PTZ) is a selective antagonist of GABAA chloride ionophore complex and stimulates epileptogenic activity by inhibiting GABA-mediated transmission [15]. Anatomically, it has been shown that the 5-HT7 receptor is expressed in all subfields of the hippocampus, especially in the CA3 and dentate gyrus regions [16]. Moreover, evidence show that 5-HT7 receptors modulate GABAergic transmission in rat hippocampal CA1 area [17]. These data suggest that GABAergic activity may play a role in the effects of the 5-HT7 receptor on seizure control. Besides, in the rat hippocampus, PTZ increased the expression of c-Fos, an immediate early gene, which is an indicator of increased neuronal activity [18]. Therefore, the aim of this study was to investigate the effect of SB-269970, a 5-HT7 antagonist, on seizure parameters, c-Fos expression and GABA levels in hippocampus in PTZ-induced fully kindled rats.
Advancements in neuroactive peptides in seizures
Published in Expert Review of Neurotherapeutics, 2022
Slobodan M. Janković, Miralem Đešević
Numerous neuroactive peptides with pro- or anti-convulsant properties are numerous, and it is likely that this group will receive new members in the future. Since the structure and function of receptors for the great majority of neuroactive peptides are known, with modern technical aids available (in silico drug discovery tools, DNA-encoded solid-phase synthesis, high-throughput screening techniques, etc.) large scale synthesis of new non-peptide agonists and antagonists of receptors for neuropeptides seems feasible. Testing of new agonists and antagonists in vitro and in animal models of epilepsy is also technically possible, since these experimental methods are well established and validated many times. Insufficient funding of research in this area is probably the only obstacle in the way of preparing new candidate molecules for clinical trials involving patients with therapy resistant epilepsy.
Cognitive impairment profile differences in patients with psychogenic non-epileptic seizures and epilepsy patients with generalized seizures
Published in Neurological Research, 2020
Özgül Karaaslan, Mehmet Hamamcı
The MoCA test has a sensitivity of 90% in detecting cognitive impairment [22]. Hyperactive neurons require high energy to produce a continuously synchronized activation during seizures. Therefore, during seizure activity, the basal oxygen level must exceed 200% in order to meet the oxygen demand of the neurons [23]. Gualtieri et al. [24] found that HIF-1α levels increased in cells exposed to hypoxia as a result of recurrent seizures, and HIF-1α levels increased in surgical material of patients with drug-resistant temporal lobe epilepsy. At the same time, they demonstrated that HIF-1α activates the caspase system and causes apoptosis in neurons. Other animal models of epilepsy support the evidence that epilepsy and seizures have negative effects on brain structure and behaviours [25]. The degree of brain damage depends on the number, duration, and severity of the seizures [26]. Although ictal and postictal cognitive dysfunction is reversible, a commonly held position is that it may lead to a progressive mental decline due to a higher frequency of seizures and the presence of chronic and uncontrolled epilepsy [27]. On the other hand, another animal study conducted after this study reported that pre-exposure of the brain to hypoxia reduces the loss of neurons in subsequent seizures and that cognitive impairment is less common [28]. When the results of our study were evaluated together with the results of the other studies, we found that perhaps the brain is more affected by hypoxia since it is not yet accustomed to it at the first seizure. Although recurrent and resistant seizures cause an increase in substances that stimulate the mechanism of apoptosis, exposure to recurrent hypoxia can also activate the brain’s self-protection mechanisms and cause less damage in subsequent seizures.