scholarly journals Experimental models of epilepsy

2004 ◽  
Vol 57 (7-8) ◽  
pp. 359-362 ◽  
Author(s):  
Olivera Stanojlovic ◽  
Dragana Zivanovic

Introduction An epileptic seizure is a clinical event and epilepsy is rather a group of symptoms than a disease. The main features all epilepsies have in common include: spontaneous occurrence, repetitiveness, and ictal correlation within the EEG. Epilepsies are manifested with distinct EEG changes, requiring exact clinical definition and consequential treatment. Current data show that 1% of the world's population (approximately 50 million people) suffers from epilepsy, with 25% of patients being refractory to therapy and requiring search for new substances in order to decrease EEG and behavioral manifestations of epilepsies. Material and methods In regard to discovery and testing of anticonvulsant substances the best results were achieved by implementation of experi- mental models. Animal models of epilepsy are useful in acquiring basic knowledge regarding pathogenesis, neurotransmitters (glutamate), receptors (NMDA/AMPA/kainate), propagation of epileptic seizures and preclinical assessment of antiepileptics (competitive and non-competitive NMDA antagonists). Results and conclusions In our lab, we have developed a pharmacologic model of a (metaphit, NMDA and remacemide-cilastatin) generalized, reflex, and audiogenic epilepsy. The model is suitable for testing various anticonvulsant substances (e.g. APH, APV, CPP, Mk-801) and potential antiepileptics (e.g. DSIP, its tetra- and octaanalogues).

2012 ◽  
Vol 64 (3) ◽  
pp. 1207-1216 ◽  
Author(s):  
D. Hrncic ◽  
Aleksandra Rasic-Markovic ◽  
Jelica Bjekic-Macut ◽  
Veselinka Susic ◽  
D. Mladenovic ◽  
...  

Epilepsy is one of the leading neurological disorders and affects 1-2% of the world?s population. Generally, it is a result of an imbalance between excitatory and inhibitory phenomena in the central nervous system (CNS), but the mechanisms of its initiation and propagation still require further investigations. Experimental models represent one of the most powerful tools to better understand the mechanisms of epileptogenesis. Nitric oxide (NO) is gaseous molecule with pleiotropic physiological and pathological effects in almost all organ systems and intriguing biological relevance, especially in the CNS where it acts as a gaseous neurotransmitter. The role of NO in the generation of epilepsy is highly contradictory, since there is evidence of its anticonvulsive, as well as proconvulsive properties. Therefore, we will discuss in this review the involvement of NO-mediated signaling pathways in the mechanisms of epileptogenesis, taking into account the findings revealed in experimental studies on animal models of epilepsy.


Neurology ◽  
2019 ◽  
Vol 93 (13) ◽  
pp. e1248-e1259 ◽  
Author(s):  
Julie Uchitel ◽  
Ashley Helseth ◽  
Lyndsey Prange ◽  
Melissa McLean ◽  
Ryan Ghusayni ◽  
...  

ObjectiveTo report our experience and investigate 5 original hypotheses: (1) multiple types of epileptic seizures occur in alternating hemiplegia of childhood (AHC), and these can be the initial presentation; (2) epileptiform abnormalities often appear well after clinical seizures; (3) nonepileptic reduced awareness spells (RAS) occur frequently; (4) epilepsy is commonly drug resistant but may respond to vagal nerve stimulation (VNS); and (5) status epilepticus (SE) is common and is usually refractory and recurrent.MethodsWe analyzed a cohort of 51 consecutive patients with AHC.ResultsThirty-two of 51 patients had epilepsy: 18 focal seizures, frontal more frequently than temporal, and then posterior. Eleven had primary generalized seizures (tonic-clonic, myoclonic, and/or absence). Epileptic seizures preceded other AHC paroxysmal events in 8 (lag 5.63 ± 6.55 months; p = 0.0365). In 7 of 32, initial EEGs were normal, with the first epileptiform EEG lagging behind by 3.53 ± 4.65 years (p = 0.0484). RAS occurred equally in patients with epilepsy (16 of 32) and patients without epilepsy (10 of 19, p = 1.0). Twenty-eight patients had video-EEG; captured RAS showed no concomitant EEG changes. Nineteen patients (59%) were drug resistant. VNS resulted in >50% reduction in seizures in 5 of 6 (p < 0.04). Twelve patients (38%) had SE (9 of 12 multiple episodes), refractory/superrefractory in all (p < 0.001), and 4 of 12 had regression after SE.ConclusionsEpilepsy in AHC can be focal or generalized. Epileptic seizures may be the first paroxysmal symptom. EEG may become epileptiform only on follow-up. Epilepsy, although frequently drug resistant, can respond to VNS. RAS are frequent and nonepileptic. SE often recurs and is usually refractory/superrefractory. Our observations are consistent with current data on AHC-ATP1A3 pathophysiology.


2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Soomaayeh Heysieattalab ◽  
Leila Sadeghi

Abstract Background The role of neuroplasticity in epilepsy has been widely studied in experimental models and human brain samples. However, the results are contradictory and it remains unclear if neuroplasticity is more related to the cause or the consequence of epileptic seizures. Clarifying this issue can provide insights into epilepsy therapies that target the disease mechanism and etiology rather than symptoms. Therefore, this study was aimed to investigate the dynamic changes of structural plasticity in a pilocarpine rat model of epilepsy. Methods A single acute dose of pilocarpine (380 mg/kg, i.p.) was injected into adult male Wistar rats to induce status epilepticus (SE). Animal behavior was monitored for 2 h. Immunohistochemical staining was performed to evaluate neurogenesis in the CA3 and dentate gyrus (DG) regions of hippocampus using biomarkers Ki67 and doublecortin (DCX). The Golgi-Cox method was performed to analyze dendritic length and complexity. All experiments were performed in control rats (baseline), at 24 h after SE, on day 20 after SE (latent phase), after the first and 10th spontaneous recurrent seizures (SRS; chronic phase), and in non-epileptic rats (which did not manifest SRS 36 days after pilocarpine injection). Results SE significantly increased the number of Ki67 and DCX-positive cells, suggesting neurogenesis during the latent phase. The dendritic complexity monitoring showed that plasticity was altered differently during epilepsy and epileptogenesis, suggesting that the two processes are completely separate at molecular and physiological levels. The numbers of spines and mushroom-type spines were increased in the latent phase. However, the dendritogenesis and spine numbers did not increase in rats that were unable to manifest spontaneous seizures after SE. Conclusion All parameters of structural plasticity that increase during epileptogenesis, are reduced by spontaneous seizure occurrence, which suggests that the development of epilepsy involves maladaptive plastic changes. Therefore, the maladaptive plasticity biomarkers can be used to predict epilepsy before development of SRS in the cases of serious brain injury.


2021 ◽  
Vol 22 (9) ◽  
pp. 4557
Author(s):  
Alessio Gerussi ◽  
Ambra Natalini ◽  
Fabrizio Antonangeli ◽  
Clara Mancuso ◽  
Elisa Agostinetto ◽  
...  

Drug-induced liver injury (DILI) is a challenging clinical event in medicine, particularly because of its ability to present with a variety of phenotypes including that of autoimmune hepatitis or other immune mediated liver injuries. Limited diagnostic and therapeutic tools are available, mostly because its pathogenesis has remained poorly understood for decades. The recent scientific and technological advancements in genomics and immunology are paving the way for a better understanding of the molecular aspects of DILI. This review provides an updated overview of the genetic predisposition and immunological mechanisms behind the pathogenesis of DILI and presents the state-of-the-art experimental models to study DILI at the pre-clinical level.


2021 ◽  
Vol 9 (4) ◽  
pp. 868
Author(s):  
Max Maurin ◽  
Florence Fenollar ◽  
Oleg Mediannikov ◽  
Bernard Davoust ◽  
Christian Devaux ◽  
...  

SARS-CoV-2 is currently considered to have emerged from a bat coronavirus reservoir. However, the real natural cycle of this virus remains to be elucidated. Moreover, the COVID-19 pandemic has led to novel opportunities for SARS-CoV-2 transmission between humans and susceptible animal species. In silico and in vitro evaluation of the interactions between the SARS-CoV-2 spike protein and eucaryotic angiotensin-converting enzyme 2 (ACE2) receptor have tentatively predicted susceptibility to SARS-CoV-2 infection of several animal species. Although useful, these data do not always correlate with in vivo data obtained in experimental models or during natural infections. Other host biological properties may intervene such as the body temperature, level of receptor expression, co-receptor, restriction factors, and genetic background. The spread of SARS-CoV-2 also depends on the extent and duration of viral shedding in the infected host as well as population density and behaviour (group living and grooming). Overall, current data indicate that the most at-risk interactions between humans and animals for COVID-19 infection are those involving certain mustelids (such as minks and ferrets), rodents (such as hamsters), lagomorphs (especially rabbits), and felines (including cats). Therefore, special attention should be paid to the risk of SARS-CoV-2 infection associated with pets.


2017 ◽  
Vol 75 ◽  
pp. 56-59 ◽  
Author(s):  
Muhammad Usama Ashhar ◽  
Mohd. Zubair Ahmad ◽  
Vikas Jain ◽  
Nidhi B. Agarwal ◽  
Farhan J. Ahmad ◽  
...  

Author(s):  
Ludmyla Kandratavicius ◽  
Priscila Balista ◽  
Cleiton Lopes-Aguiar ◽  
Rafael Ruggiero ◽  
Eduardo Umeoka ◽  
...  

2019 ◽  
Vol 10 (4) ◽  
pp. 26-38
Author(s):  
G. G. Avakyan ◽  
T. A. Voronina ◽  
L. N. Nerobkova ◽  
G. N. Avakyan

The aimis to develop an antiepileptic drug based on polymer nanoparticles with 2-ethyl-6-methyl-3-oxypyridine succinate to facilitate the drug transport through the blood-brain barrier.Materials and methods.The nano-drug was created using the biologically active substance 2-ethyl-6-methyl-3-hydroxypyridine succinate and polybutyl cyanoacrylate (PBCA) nanoparticles. The advantages of this nano-form over the active ingredient of the same drug were studied using experimental models: the maximum electroshock test (MES), the antagonism test with corazol, models with a cobaltinduced epileptic focus and secondary generalized convulsions, and models of status epilepticus.Results.The antiseizure effects of the nanoform on the experimental models of epilepsy are identified.Conclusion.The nano-drug reduces the number of secondary generalized clonic-tonic seizures by 7.8 times; it also reduces 10-fold the animal mortality and diminishes the seizure manifestations that occur in the interictal period of the epileptic status.


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