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Auteur : Grafiati
Publié le 11 mars 2023

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1

Габова, А. В., К. Ю. Саркисова, Е. А. Федосова, А. Б. Шацкова et А. А. Морозов. « ВОЗРАСТНЫЕ ИЗМЕНЕНИЯ ПИК-ВОЛНОВЫХ РАЗРЯДОВ У КРЫС ЛИНИИ WAG/Rij С ГЕНЕТИЧЕСКОЙ АБСАНСНОЙ ЭПИЛЕПСИЕЙ, "Российский физиологический журнал им. И.М. Сеченова" ». Российский физиологический журнал им. И. М. Сеченова, no 10 (2018) : 1176–89. http://dx.doi.org/10.7868/s0869813918100052.

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Крысы линии WAG/Rij являются моделью генетической абсансной эпилепсии, характеризующейся наличием пик-волновых разрядов (ПВР) на ЭЭГ. Известно, что первые ПВР у крыс линии WAG/Rij возникают в возрасте 2-3 месяцев, а в дальнейшем их число и длительность увеличиваются. Однако эволюция ПВР в процессе прогрессивного развития абсансной эпилепсии у крыс линии WAG/Rij остается неисследованной. Цель настоящей работы - выяснить возрастные изменения частотно-временной динамики, частотного спектра и морфологических характеристик ПВР у крыс линии WAG/Rij. Для достижения этой цели у одних и тех же крыс в возрасте от 2 до 12 месяцев исследовали эволюцию ПВР. Установлено, что ПВР формируются в возрасте 2-4 месяцев, в дальнейшем наблюдают морфологические изменения ПВР. Показано, что в процессе прогрессивного развития абсансной эпилепсии ПВР проходят 3 стадии «созревания». Предполагается, что связанная с возрастом эволюция ПВР у крыс линии WAG/Rij является отражением прогрессивных электрофизиологических изменений в соматосенсорной коре - области мозга, с которой связывают генерацию и генерализацию ПВР.
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Zhuravlev, Maxim, Anastasiya Runnova, Kirill Smirnov et Evgenia Sitnikova. « Spike-Wave Seizures, NREM Sleep and Micro-Arousals in WAG/Rij Rats with Genetic Predisposition to Absence Epilepsy : Developmental Aspects ». Life 12, no 4 (12 avril 2022) : 576. http://dx.doi.org/10.3390/life12040576.

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The current study was done in Wistar Albino Glaxo Rijswijk (WAG/Rij) rats, which are genetically prone to develop spontaneous spike-wave discharges (SWDs) and are widely used as a genetic model of absence epilepsy. Here, we examined functional links between sleep and spike-wave epilepsy in aging WAG/Rij rats using advanced techniques of EEG analysis. SWDs, periods of NREM sleep and micro-arousals were automatically detected in three-channel epidural EEG recorded in freely moving WAG/Rij rats consequently at the age 5, 7 and 9 months. We characterized the developmental profile of spike-wave epilepsy in drug-naïve WAG/Rij rats and defined three epi-phenotypes—severe, mild and minor epilepsy. Age-related changes of SWDs were associated with changes in NREM sleep. Several signs of NREM sleep fragmentation were defined in epileptic WAG/Rij rats. It seems that spike-wave epilepsy per se promotes micro-arousals during NREM sleep. However, subjects with a higher number of micro-arousals (and NREM sleep episodes) at the age of 5 months were characterized by a reduction of SWDs between 5 and 7 months of age.
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Ilbay, Gul, Aymen Balıkcı, Sibel Köktürk, Melda Yardımoglu Yılmaz, Nurbay Ates, Canan Baydemır et Sibel Balcı. « Neonatal Tactile Stimulation Downregulates Dendritic Spines in Layer V Pyramidal Neurons of the WAG/Rij Rat Somatosensory Cortex ». Neural Plasticity 2022 (12 avril 2022) : 1–9. http://dx.doi.org/10.1155/2022/7251460.

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Objective. The aim of our study is to examine the effects of neonatal tactile stimulations on the brain structures that previously defined as the focus of epilepsy in the Wistar-Albino-Glaxo from Rijswijk (WAG/Rij) rat brain with genetic absence epilepsy. Methods. In the present research, morphology and density of dendritic spines were analyzed in layer V pyramidal neurons of the somatosensory cortex (SoCx) of WAG/Rij rats (nonstimulated control, tactile-stimulated, and maternal separated rats) and healthy Wistar (nonepileptic) rats. To achieve this, a Golgi-Cox method was used. Results. Dendritic spine number in layer V of the SoCx has been detected significantly higher in adult WAG/Rij rats at postnatal day 150 in comparison to nonepileptic adult control Wistar rats ( p < 0.001 ). Moreover, quantitative analyses of dendrite structure in adult WAG/Rij rats showed a decrease in dendrite spine density of pyramidal neurons of SoCx which occurred in early neonatal exposure to maternal separation (MS) and tactile stimulation (TS) ( p < 0.001 ). Conclusions. Our findings provide the first evidence that tactile stimulations during the early postnatal period have a long-term impact on dendrite structure in WAG/Rij rat’s brain and demonstrate that neonatal tactile stimulation can regulate dendritic spines in layer V in pyramidal neurons of SoCx in epileptic brains.
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Musina, L. A., S. S. Baigil'din et Z. R. Khismatullina. « Morphological study of the retina of WAG/Rij rats with pigmentary degeneration in postnatal ontogenesis ». Journal of Anatomy and Histopathology 9, no 3 (10 octobre 2020) : 42–48. http://dx.doi.org/10.18499/2225-7357-2020-9-3-42-48.

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The aim of the study was to detect morphofunctional features of the retina of WAG/Rij rats during postnatal development from the 1st to the 360th day after birth.Material and methods. The study included retina of the inbred WAG/Rij rats (60 eyeballs from 30 rats totally) from the 1st to the 360th day of life. Standard histological studies were performed on paraffin sections stained with hematoxylin and eosin. Immunohistochemical method was used to determine the expression of acidic glial fibrillar protein GFAP in the rat retina. Mouse monoclonal antibodies (Santa Cruz Biotechnology) and a universal secondary detection system (NovocastraTM) were used for imaging. The degree of protein expression in the retina of WAG/Rij rats was compared in different age groups.Results. It was found that after birth, the retina of rat models of the WAG/Rij line is formed in the same way as the retina of rats of other strains and acquires a definitive structure only by the end of the second week (correlates with the opening of the eyes). On the 20th day, the first signs of dystrophic and destructive processes appear in the retina of WAG / Rij rats progressing as they grow older and leading to retinal gliosis. The increase in the expression of acidic glial fibrillar protein GFAP begins from the 30th day and increases with age as destructive processes in the retina increase. Conclusion. The early postnatal development of the retina of the WAG/Rij rats, which correlates in character with the postnatal retina development of rats of other strains, is interrupted by the launch of destructive processes in the retina soon after its complete differentiation. The further intensifying cascade of degeneration over time leads to the death of retinal neurons and their replacement by glial cells.
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Celikyurt, Ipek Komsuoglu, Guner Ulak, Oguz Mutlu, Furuzan Yildiz Akar, Faruk Erden et Sezer Sener Komsuoglu. « Lamotrigine effects sensorimotor gating in WAG/Rij rats ». Journal of Neurosciences in Rural Practice 03, no 02 (mai 2012) : 126–30. http://dx.doi.org/10.4103/0976-3147.98207.

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ABSTRACTIntroduction: Prepulse inhibition (PPI) is a measurable form of sensorimotor gating. Disruption of PPI reflects the impairment in the neural filtering process of mental functions that are related to the transformation of an external stimuli to a response. Impairment of PPI is reported in neuropsychiatric illnesses such as schizophrenia, Huntington’s disease, Parkinson’s diseases, Tourette syndrome, obsessive compulsive disorder, and temporal lobe epilepsy with psychosis. Absence epilepsy is the most common type of primary generalized epilepsy. Lamotrigine is an antiepileptic drug that is preferred in absence epilepsy and acts by stabilizing the voltage-gated sodium channels. Aim: In this study, we have compared WAG-Rij rats (genetically absence epileptic rats) with Wistar rats, in order to clarify if there is a deficient sensorimotor gating in absence epilepsy, and have examined the effects of lamotrigine (15, 30 mg/kg, i.p.) on this phenomenon. Materials and Methods: Depletion in PPI percent value is accepted as a disruption in sensory-motor filtration function. The difference between the Wistar and WAG/Rij rats has been evaluated with the student t test and the effects of lamotrigine on the PPI percent have been evaluated by the analysis of variance (ANOVA) post-hoc Dunnett’s test. Results: The PPI percent was low in the WAG/Rij rats compared to the controls (P<0.0001, t:9,612). Although the PPI percent value of the control rats was not influenced by lamotrigine, the PPI percent value of the WAG/Rij rats was raised by lamotrigine treatment (P<0.0001, F:861,24). Conclusions: As a result of our study, PPI was disrupted in the WAG/Rij rats and this disruption could be reversed by an antiepileptic lamotrigine.
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Ilbay, Gul, Zeynep Ikbal Dogan, Aymen Balıkcı, Seyda Erdogan et Akfer Karaoglan Kahilogulları. « Effects of Postnatal Caffeine Exposure on Absence Epilepsy and Comorbid Depression : Results of a Study in WAG/Rij Rats ». Brain Sciences 12, no 3 (8 mars 2022) : 361. http://dx.doi.org/10.3390/brainsci12030361.

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The present study aims to investigate effect of early caffeine exposure on epileptogenesis and occurrence of absence seizures and comorbid depression in adulthood. For this purpose, Wistar Albino Glaxo from Rijswijk (WAG/Rij) rats were enrolled in a control and two experimental groups on the 7th day after the delivery. The rats in experimental groups received either 10 or 20 mg/kg caffeine subcutaneously while animals in control group had subcutaneous injections of 0.9% saline. The injections started at postnatal day 7 (PND7) and were continued each day for 5 days. At 6–7 months of age, electroencephalogram (EEG) recordings and behavioral recordings in the forced swimming test, sucrose consumption/preference test and locomotor activity test were carried out. At 6 months of age, 10 mg/kg and 20 mg/kg caffeine-treated WAG/Rij rats showed increased immobility latency and active swimming duration in forced swimming test when compared with the untreated controls. In addition, 20 mg/kg caffeine treatment decreased immobility time. In sucrose preference/consumption tests, WAG/Rij rats in 10 mg/kg caffeine group demonstrated higher sucrose consumption and preference compared to untreated controls. The rats treated with 20 mg/kg caffeine showed higher sucrose preference compared to control rats. The exploratory activity of rats in the 10 mg/kg caffeine-treated group was found to be higher than in the 20 mg/kg caffeine-treated and control groups in the locomotor activity test. At 7 months of age, caffeine-treated animals showed a decreased spike-wave discharge (SWD) number compared to the control animals. These results indicate that postnatal caffeine treatment may decrease the number of seizure and depression-like behaviors in WAG/Rij rats in later life. Caffeine blockade of adenosine receptors during the early developmental period may have beneficial effects in reducing seizure frequency and depression-like behaviors in WAG/Rij rat model.
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De Miguel, M., J. M. Fernández-Santos, I. Trigo-Sánchez, I. Matera, I. Ceccherini, I. Martín, G. Romeo et H. Galera-Davidson. « The Ret proto-oncogene in the WAG/Rij rat strain : an animal model for inherited C-cell carcinoma ? » Laboratory Animals 37, no 3 (1 juillet 2003) : 215–21. http://dx.doi.org/10.1258/002367703766453065.

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WAG/Rij rat strain has been suggested as an animal model for the study of inherited human medullary thyroid carcinoma (MTC), due to its high incidence of spontaneous C-cell thyroid tumours. Although the role of the Ret proto-oncogene mutations, as responsible for human MTC, is well established, nothing has been published concerning this putative animal model. Based upon the previously reported rat Ret sequence, exons 10, 11, 13, 14, 15, and 16, known to carry activating mutations in humans, have been analysed in the WAG/Rij rat by PCR, single strand conformational polymorphism (SSCP) and direct sequencing. Neither the germline nor MTC samples showed any Ret sequence difference in the exons when analysed in comparison to a non-MTC-susceptible rat strain. Our results indicate that Ret exons relevant in humans are not involved in WAG/Rij rat MTC, as expected, and this questions the validity of this strain as a model for the human disease, and suggests there must be additional mechanisms for the genesis and progression of rat MTC.
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Poolos, Nicholas P. « H-Channel Dysfunction in Generalized Epilepsy : It Takes Two ». Epilepsy Currents 6, no 3 (mai 2006) : 88–90. http://dx.doi.org/10.1111/j.1535-7511.2006.00107.x.

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Impaired Regulation of Thalamic Pacemaker Channels Through an Imbalance of Subunit Expression in Absence Epilepsy Budde T, Caputi L, Kanyshkova T, Staak R, Abrahamczik C, Munsch T, Pape HC J Neurosci 2005;25(43):9871–9882 The role of hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channel isoforms and hyperpolarization-activated cation current ( Ih) for seizure-related burst firing in thalamocortical (TC) neurons was investigated in a rat genetic model of absence epilepsy [Wistar Albino Glaxo rats, bred in Rijswijk (WAG/Rij)]. Burst discharges in TC neurons locked to seizure activity in vivo were prolonged during blockade of Ih by Cs+ and ZD7288 (4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium chloride). In vitro analyses revealed a hyperpolarizing shift of half-maximal Ih activation ( Vh) in WAG/Rij ( Vh = −93.2 mV) compared with nonepileptic controls [August × Copenhagen-Irish (ACI) ( Vh = −88.0 mV)]. This effect is explained by a shift of the responsiveness of Ih to cAMP toward higher concentrations in TC neurons from WAG/Rij, as revealed by application of 8-bromo-cAMP and the phosphodiesterase inhibitor IBMX. During blockade of adenylyl cyclase activity, Ih activation was similar in the two strains, whereas the difference in cAMP responsiveness persisted, thereby voting against different ambient cAMP levels between strains. Increasing the intracellular cAMP level and shifting Ih activation led to a change from burst to tonic firing mode in WAG/Rij but not in ACI rats. Furthermore, HCN1 expression was significantly increased on mRNA and protein levels, with no changes in HCN2–4 expression. In conclusion, there is an increase in HCN1 expression in the epileptic thalamus, associated with a decrease in cAMP responsiveness of Ih in TC neurons and resulting impairment to control the shift from burst to tonic firing, which, in turn, will prolong burst activity after recruitment of Ih during absence seizures.
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Sitnikova, Evgenia, Alexander E. Hramov, Vadim Grubov et Alexey A. Koronovsky. « Age-Dependent Increase of Absence Seizures and Intrinsic Frequency Dynamics of Sleep Spindles in Rats ». Neuroscience Journal 2014 (23 juin 2014) : 1–6. http://dx.doi.org/10.1155/2014/370764.

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The risk of neurological diseases increases with age. In WAG/Rij rat model of absence epilepsy, the incidence of epileptic spike-wave discharges is known to be elevated with age. Considering close relationship between epileptic spike-wave discharges and physiologic sleep spindles, it was assumed that age-dependent increase of epileptic activity may affect time-frequency characteristics of sleep spindles. In order to examine this hypothesis, electroencephalograms (EEG) were recorded in WAG/Rij rats successively at the ages 5, 7, and 9 months. Spike-wave discharges and sleep spindles were detected in frontal EEG channel. Sleep spindles were identified automatically using wavelet-based algorithm. Instantaneous (localized in time) frequency of sleep spindles was determined using continuous wavelet transform of EEG signal, and intraspindle frequency dynamics were further examined. It was found that in 5-months-old rats epileptic activity has not fully developed (preclinical stage) and sleep spindles demonstrated an increase of instantaneous frequency from beginning to the end. At the age of 7 and 9 months, when animals developed matured and longer epileptic discharges (symptomatic stage), their sleep spindles did not display changes of intrinsic frequency. The present data suggest that age-dependent increase of epileptic activity in WAG/Rij rats affects intrinsic dynamics of sleep spindle frequency.
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ÇELİK, Zülfinaz Betül, Emre Soner TİRYAKİ, Elif TÜRKDÖNMEZ, M. Nusret ÇİÇEKLİ, Ahmet ALTUN et Caner GÜNAYDIN. « Parallel changes in the promoter methylation of voltage-gated T-type calcium channel alpha 1 subunit G and histone deacetylase activity in the WAG/Rij model of absence epilepsy ». Journal of Health Sciences and Medicine 6, no 1 (12 janvier 2023) : 92–98. http://dx.doi.org/10.32322/jhsm.1207399.

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Objective: In the last two decades, research on epigenetic mechanisms has expanded dramatically. Recent studies demonstrated that epigenetic mechanisms regulate epilepsy and epileptogenic pathologies. In this study, we aimed to investigate changes in the promoter methylation status of the voltage-gated T-type calcium channel alpha 1 subunit G (CACNA1G) gene and total histone deacetylase activity in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats which is one of the commonly used genetic absence rat models of epilepsy in the three different age groups (3, 6, and 9 months old) on both sexes. Material and Method: Evaluation of changes in the spike-wave discharges (SWDs) was performed with electrocorticography (ECoG). The promoter methylation status of the CACNA1G gene was determined by methylation-specific PCR (MSP), and histone deacetylase (HDAC) activity was determined spectrophotometrically. Results: Our results demonstrated that the number of SWDs increased time-dependent in WAG/Rij. Additionally, it was observed that CACNA1G promoter methylation decreased, and total HDAC activity increased with age in both sexes. Conclusion: Our results provide further support for epigenetic regulation in the absence epilepsy phenotype and suggest that the underlying mechanism behind the increase in the number of SWDs with age in the WAG/Rij animals might be regulated by CACNA1G promoter methylation or HDAC activity.
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Sarkisova, Karine Yu, Ekaterina A. Fedosova, Alla B. Shatskova, Margarita M. Rudenok, Vera A. Stanishevskaya et Petr A. Slominsky. « Maternal Methyl-Enriched Diet Increases DNMT1, HCN1, and TH Gene Expression and Suppresses Absence Seizures and Comorbid Depression in Offspring of WAG/Rij Rats ». Diagnostics 13, no 3 (21 janvier 2023) : 398. http://dx.doi.org/10.3390/diagnostics13030398.

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The reduced expression of the HCN1 ion channel in the somatosensory cortex (SSC) and mesolimbic dopamine deficiency are thought to be associated with the genesis of spike-wave discharges (SWDs) and comorbid depression in the WAG/Rij rat model of absence epilepsy. This study aimed to investigate whether the maternal methyl-enriched diet (MED), which affects DNA methylation, can alter DNMT1, HCN1, and TH gene expression and modify absence seizures and comorbid depression in WAG/Rij offspring. WAG/Rij mothers were fed MED (choline, betaine, folic acid, vitamin B12, L-methionine, zinc) or a control diet for a week before mating, during pregnancy, and for a week after parturition. MED caused sustained suppression of SWDs and symptoms of comorbid depression in the offspring. Disease-modifying effects of MED were associated with increased expression of the DNMT1 and HCN1 genes in the SSC and hippocampus, as well as DNMT1, HCN1, and TH genes in the nucleus accumbens. No changes in gene expression were detected in the hypothalamus. The results indicate that maternal MED can suppress the genetic absence epilepsy and comorbid depression in offspring. Increased expression of the DNMT1, HCN1, and TH genes is suggested to be a molecular mechanism of this beneficial phenotypic effect.
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Sitnikova, E. Yu, K. S. Smirnov, V. V. Grubov et A. E. Hramov. « Diagnostic principles of immature epileptic (proepileptic) EEG activity in rats with genetic predisposition to absence epilepsy ». Information and Control Systems, no 1 (19 février 2019) : 89–97. http://dx.doi.org/10.31799/1684-8853-2019-1-89-97.

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Introduction:Absence epilepsy is a specific neurological disorder characterized by brief episodes of loss of consciousness (absence) accompanied by high-amplitude “spike-wave” discharges in the electroencephalogram (EEG). WAG/Rij rats with a genetic predisposition to absence epilepsy are used as a reliable model of this disease. This model is beneficial for investigating basic mechanisms of absence epilepsy, including the development of spike-wave seizures.Purpose:Establishing diagnostic principles for immature forms of spikewave activity in EEG (so-called proepileptic activity) of WAG/Rij rats.Results:Diagnostic criteria are proposed for proepileptic EEG activity in rats, based on time-frequency analysis with the continuous wavelet transform and skeletons of wavelet surfaces. The algorithm was tested in “epileptic” and “asymptomatic” individuals. Rats with the “epileptic” phenotype demonstrated a decrease in number of proepileptic patterns between 5 and 7 months of age in parallel to an increase in the number of epileptic discharges that might relate to the transformation of proepileptic activity to epileptic. In rats with the “asymptomatic” phenotype, the age-related decline in the number of proepileptic patterns was not accompanied by the occurrence of spike-wave discharges. A decrease in the instantaneous frequency was found in a larger number of proepileptic patterns in “epileptic” WAG/Rij rats as compared to “asymptomatic” individuals.Practical relevance:A similar approach can be used for early diagnosis of absence epilepsy at the preclinical stage in patients with genetic predisposition.
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Tolmacheva, Elena A., Serguei A. Chepurnov, Nina E. Chepurnova, Yakov A. Kochetkov et Gilles van Luijtelaar. « Absence seizures during pregnancy in WAG/Rij rats ». Physiology & ; Behavior 81, no 4 (juin 2004) : 623–27. http://dx.doi.org/10.1016/j.physbeh.2004.02.028.

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Луїджтелаар, Дж. ван, et Дж. ван Ойджен. « СУЧАСНІ ПРИНЦИПИ ТА ТЕХНІЧНЕ ЗАБЕЗПЕЧЕННЯ ДОСЛІДЖЕНЬ НА МОДЕЛІ ГЕНЕТИЧНОЇ ФОРМИ АБСАНСНОЇ ЕПІЛЕПСІЇ ». Medical Informatics and Engineering, no 1 (22 juin 2020) : 45–65. http://dx.doi.org/10.11603/mie.1996-1960.2020.1.11129.

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Визначення валідної експериментальної моделі абсансної епілепсії є важливим як по відношенню до вивчення механізмів заховарювання, так і обґрунтування методів його лікування. Генетичні моделі WAG/Rij та GAERS створено як моделі генералізованої генетично детермінованої форми епілепсії, що відображають особливості абсансної епілепсії дитячого віку та на сьогодні являються провідними щодо визначення причин походження абсансної епілепсії. В огляді літератури наведено узагальнення 40-річного досвіду роботи з питань вивчення експериментальної абсансної епілепсії з метою визначення найбільш оптимального протоколу оцінювання методів лікування, впливу лікарських засобів на електроенцефалограму в щурів лінії WAG/Rij. Зазначені моделі описано у восьмидесяті роки минулого сторіччя, коли й визначено їхню валідність щодо відтворення особливостей абсансної епілепсії. Наразі вказані моделі використовують для визначення ефектів антиепілептичних препаратів та інших засобів припинення епілептичної активності, а також для вивчення нейробіологічних механізмів розвитку спайк-хвильвоих розрядів та епілептогенезу. Хоча для визначення діагнозу абсансної епілепсії ключовими є реєстрація електроенцефалограми, електрокортикограми важливим залишається також дослідження відповідних поведінкових проявів. У роботі наведено протоколи дослідження ефективністі лікарських засобів, зокрема вейвлет аналіз і різні методи застосування нейронних мереж, необхідність моніторингу та кількісного оцінювання поведінки під час реєстрації електроенцефалограм, застереження щодо аналізу результатів, а також новітні методи електроенцефалограм-технологій. Генетичні моделі витіснили моделі судом, викликані лікарськими засобами, що дозволяє проводити дослідження за умов вихідної епілептизації мозку та з розумінням внеску моделей викликаних іншими засобами. Предиктивна ефективність генетичних моделей перевищує таку в моделей, викликаних епілептогенними чинниками. Комбінована електроенцефалограма та поведінкова реєстрація у WAG/Rij щурів незалежно від їхньої статі має високий потенціал визначення про- та антиепілептогенної ефективності досліджуваних методів експериментального лікування.
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Knowles, Juliet K., Haojun Xu, Caroline Soane, Ankita Batra, Tristan Saucedo, Eleanor Frost, Lydia T. Tam et al. « Maladaptive myelination promotes generalized epilepsy progression ». Nature Neuroscience 25, no 5 (mai 2022) : 596–606. http://dx.doi.org/10.1038/s41593-022-01052-2.

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AbstractActivity-dependent myelination can fine-tune neural network dynamics. Conversely, aberrant neuronal activity, as occurs in disorders of recurrent seizures (epilepsy), could promote maladaptive myelination, contributing to pathogenesis. In this study, we tested the hypothesis that activity-dependent myelination resulting from absence seizures, which manifest as frequent behavioral arrests with generalized electroencephalography (EEG) spike-wave discharges, promote thalamocortical network hypersynchrony and contribute to epilepsy progression. We found increased oligodendrogenesis and myelination specifically within the seizure network in two models of generalized epilepsy with absence seizures (Wag/Rij rats and Scn8a+/mut mice), evident only after epilepsy onset. Aberrant myelination was prevented by pharmacological seizure inhibition in Wag/Rij rats. Blocking activity-dependent myelination decreased seizure burden over time and reduced ictal synchrony as assessed by EEG coherence. These findings indicate that activity-dependent myelination driven by absence seizures contributes to epilepsy progression; maladaptive myelination may be pathogenic in some forms of epilepsy and other neurological diseases.
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Yildiz, Ozlem Kayim, Caglar Yildiz, Nedim Durmus, Sefa Gulturk, Selim Benek et Ali Cetin. « Ovariectomy enhances spike-wave discharges in WAG/Rij rats ». Neurology, Psychiatry and Brain Research 17, no 3 (septembre 2011) : 67–70. http://dx.doi.org/10.1016/j.npbr.2011.06.005.

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Саркисова, К. Ю., М. А. Куликов, В. С. Кудрин, В. Б. Наркевич, И. С. Мидзяновская, Л. М. Бирюкова, А. А. Фоломкина et А. С. Базян. « Нейрохимические механизмы депрессивноподобного поведения у крыс линии WAG/RIJ ». Журнал высшей нервной деятельности им. И. В. Павлова 63, no 3 (2013) : 303–15. http://dx.doi.org/10.7868/s0044467713030106.

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Renier, W. O., et A. M. L. Coenen. « Human absence epilepsy : The WAG/Rij rat as a model ». Neuroscience Research Communications 26, no 3 (2000) : 181–91. http://dx.doi.org/10.1002/1520-6769(200005/06)26:3<181 ::aid-nrc6>3.0.co;2-f.

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Malyshev, A. V., A. M. Zakharov, K. Yu Sarkisova et V. A. Dubynin. « Reversal Learning in WAG/Rij Rats with Depression-Like Behavior ». Neuroscience and Behavioral Physiology 44, no 1 (20 décembre 2013) : 36–43. http://dx.doi.org/10.1007/s11055-013-9869-y.

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Nersesyan, Hrachya, Fahmeed Hyder, Douglas L. Rothman et Hal Blumenfeld. « Dynamic fMRI and EEG Recordings during Spike-Wave Seizures and Generalized Tonic-Clonic Seizures in WAG/Rij Rats ». Journal of Cerebral Blood Flow & ; Metabolism 24, no 6 (juin 2004) : 589–99. http://dx.doi.org/10.1097/01.wcb.0000117688.98763.23.

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Generalized epileptic seizures produce widespread physiological changes in the brain. Recent studies suggest that “generalized” seizures may not involve the whole brain homogeneously. For example, electrophysiological recordings in WAG/Rij rats, an established model of human absence seizures, have shown that spike-and-wave discharges are most intense in the perioral somatosensory cortex and thalamus, but spare the occipital cortex. Is this heterogeneous increased neuronal activity matched by changes in local cerebral blood flow sufficient to meet or exceed cerebral oxygen consumption? To investigate this, we performed blood oxygen level-dependent functional magnetic resonance imaging (fMRI) measurements at 7T with simultaneous electroencephalogram recordings. During spontaneous spike-wave seizures in WAG/Rij rats under fentanylhaloperidol anesthesia, we found increased fMRI signals in focal regions including the perioral somatosensory cortex, known to be intensely involved during seizures, whereas the occipital cortex was spared. For comparison, we also studied bicuculline-induced generalized tonic-clonic seizures under the same conditions, and found fMRI increases to be larger and more widespread than during spike-and-wave seizures. These findings suggest that even in regions with intense neuronal activity during epileptic seizures, oxygen delivery exceeds metabolic needs, enabling fMRI to be used for investigation of dynamic cortical and subcortical network involvement in this disorder.
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21

Tsyba, Evgeniya T., Inna S. Midzyanovskaya, Lidia M. Birioukova, Leena M. Tuomisto, Gilles van Luijtelaar et Kenul R. Abbasova. « Striatal Patchwork of D1-like and D2-like Receptors Binding Densities in Rats with Genetic Audiogenic and Absence Epilepsies ». Diagnostics 13, no 4 (5 février 2023) : 587. http://dx.doi.org/10.3390/diagnostics13040587.

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Binding densities to dopamine D1-like and D2-like receptors (D1DR and D2DR) were studied in brain regions of animals with genetic generalized audiogenic (AGS) and/or absence (AbS) epilepsy (KM, WAG/Rij-AGS, and WAG/Rij rats, respectively) as compared to non-epileptic Wistar (WS) rats. Convulsive epilepsy (AGS) exerted a major effect on the striatal subregional binding densities for D1DR and D2DR. An increased binding density to D1DR was found in the dorsal striatal subregions of AGS-prone rats. Similar changes were seen for D2DR in the central and dorsal striatal territories. Subregions of the nucleus accumbens demonstrated consistent subregional decreases in the binding densities of D1DR and D2DR in epileptic animals, irrespective of epilepsy types. This was seen for D1DR in the dorsal core, dorsal, and ventrolateral shell; and for D2DR in the dorsal, dorsolateral, and ventrolateral shell. An increased density of D2DR was found in the motor cortex of AGS-prone rats. An AGS-related increase in binding densities to D1DR and D2DR in the dorsal striatum and motor cortex, areas responsible for motor activity, possibly reflects the activation of brain anticonvulsive loops. General epilepsy-related decreases in binding densities to D1DR and D2DR in the accumbal subregions might contribute to behavioral comorbidities of epilepsy.
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22

Luijtelaar, G., et M. Zobeiri. « Progress and Outlooks in a Genetic Absence Epilepsy Model (WAG/Rij) ». Current Medicinal Chemistry 21, no 6 (31 janvier 2014) : 704–21. http://dx.doi.org/10.2174/0929867320666131119152913.

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LaVail, M. M., D. S. Papermaster, C. D. B. Bridges, L. M. Rapp, F. Gonzalez-Fernandez et Joe G. Hollyfield. « Absence of an inherited retinal degeneration in the WAG/Rij rat ». Experimental Eye Research 44, no 3 (janvier 1987) : 465–69. http://dx.doi.org/10.1016/s0014-4835(87)80180-x.

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Midzyanovskaya, Inna S., Galina D. Kuznetsova, Liudmila V. Vinogradova, Alla B. Shatskova, Anton M. L. Coenen et Gilles van Luijtelaar. « Mixed forms of epilepsy in a subpopulation of WAG/Rij rats ». Epilepsy & ; Behavior 5, no 5 (octobre 2004) : 655–61. http://dx.doi.org/10.1016/j.yebeh.2004.06.021.

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Aker, Rezzan Gulhan, Hasan Raci Yananli, Ayten Azizova Gurbanova, Aydan Ergun Ozkaynakci, Nurbay Ates, Gilles Luijtelaar et Filiz Yilmaz Onat. « Amygdala Kindling in the WAG/Rij Rat Model of Absence Epilepsy ». Epilepsia 47, no 1 (janvier 2006) : 33–40. http://dx.doi.org/10.1111/j.1528-1167.2006.00367.x.

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Przewłocka, B., W. Lasoń, H. Machelska, G. van Luijtelaar, A. Coenen et R. Przewłocki. « Kappa opioid receptor agonists suppress absence seizures in WAG/Rij rats ». Neuroscience Letters 186, no 2-3 (février 1995) : 131–34. http://dx.doi.org/10.1016/0304-3940(95)11303-e.

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Midzyanovskaya, I., M. Kopilov, E. Fedotova, G. Kuznetsova et L. Tuomisto. « Dual effect of pyrilamine on absence seizures in WAG/Rij rats ». Inflammation Research 54, S1 (avril 2005) : S40—S41. http://dx.doi.org/10.1007/s00011-004-0418-6.

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Саркисова, К. Ю., А. В. Габова, М. А. Куликов, Е. А. Федосова, А. Б. Шацкова et А. А. Морозов. « ВОСПИТАНИЕ ПРИЕМНОЙ МАТЕРЬЮ Wistar С ВЫСОКИМ УРОВНЕМ ПРОЯВЛЕНИЯ МАТЕРИНСКОЙ ЗАБОТЫ ПРЕПЯТСТВУЕТ РАЗВИТИЮ НАСЛЕДСТВЕННОЙ АБСАНСНОЙ ЭПИЛЕПСИИ И КОМОРБИДНОЙ ДЕПРЕССИИ У КРЫС ЛИНИИ WAG/Rij, "Доклады Академии наук" ». Доклады Академии Наук, no 2 (2017) : 246–49. http://dx.doi.org/10.7868/s086956521708028x.

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Впервые показано, что воспитание приемной матерью Wistar с высоким уровнем проявления материнской заботы (МЗ) подавляет выраженность наследственной абсансной эпилепсии (АЭ) и коморбидной депрессии: уменьшает число, длительность, индекс пик-волновых разрядов (ПВР) и время иммобилизации в тесте вынужденного плавания, а также существенно влияет на морфологию и частотно-временную динамику ПВР у крыс линии WAG/Rij. Предполагается, что усиление МЗ в раннем возрасте может быть использовано для предотвращения эпилептогенеза и коморбидной депрессии у людей с генетической предрасположенностью к АЭ.
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Brunner, Brigitta, Enikő Rauch, Csilla Ari, Dominic P. D’Agostino et Zsolt Kovács. « Enhancement of Ketone Supplements-Evoked Effect on Absence Epileptic Activity by Co-Administration of Uridine in Wistar Albino Glaxo Rijswijk Rats ». Nutrients 13, no 1 (15 janvier 2021) : 234. http://dx.doi.org/10.3390/nu13010234.

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Both uridine and exogenous ketone supplements decreased the number of spike-wave discharges (SWDs) in a rat model of human absence epilepsy Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. It has been suggested that alleviating influence of both uridine and ketone supplements on absence epileptic activity may be modulated by A1 type adenosine receptors (A1Rs). The first aim was to determine whether intraperitoneal (i.p.) administration of a specific A1R antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 0.2 mg/kg) and a selective adenosine A2A receptor antagonist (7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo [1,5-c]pyrimidine) (SCH 58261; 0.5 mg/kg) have a modulatory influence on i.p. 1000 mg/kg uridine-evoked effects on SWD number in WAG/Rij rats. The second aim was to assess efficacy of a sub-effective dose of uridine (i.p. 250 mg/kg) combined with beta-hydroxybutyrate salt + medium chain triglyceride (KSMCT; 2.5 g/kg, gavage) on absence epilepsy. DPCPX completely abolished the i.p. 1000 mg/kg uridine-evoked alleviating effect on SWD number whereas SCH 58261 was ineffective, confirming the A1R mechanism. Moreover, the sub-effective dose of uridine markedly enhanced the effect of KSMCT (2.5 g/kg, gavage) on absence epileptic activity. These results demonstrate the anti-epilepsy benefits of co-administrating uridine and exogenous ketone supplements as a means to treat absence epilepsy.
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Helderman, Roxan F. C. P. A., Mauricio Tobón Restrepo, Hans M. Rodermond, Gregor G. W. van Bochove, Daan R. Löke, Nicolaas A. P. Franken, H. Petra Kok, Pieter J. Tanis, Johannes Crezee et Arlene L. Oei. « Non-Invasive Imaging and Scoring of Peritoneal Metastases in Small Preclinical Animal Models Using Ultrasound : A Preliminary Trial ». Biomedicines 10, no 7 (6 juillet 2022) : 1610. http://dx.doi.org/10.3390/biomedicines10071610.

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Background: The peritoneum is a common site for the formation of metastases originating from several gastrointestinal and gynecological malignancies. A representative preclinical model to thoroughly explore the pathophysiological mechanisms and to study new treatment strategies is important. A major challenge for such models is defining and quantifying the (total) tumor burden in the peritoneal cavity prior to treatment, since it is preferable to use non-invasive methods. We evaluated ultrasound as a simple and easy-to-handle imaging method for this purpose. Methods: Peritoneal metastases were established in six WAG/Rij rats through i.p. injections of the colon carcinoma cell line CC-531. Using ultrasound, the location, number and size of intraperitoneal tumor nodules were determined by two independent observers. Tumor outgrowth was followed using ultrasound until the peritoneal cancer index (PCI) was ≥8. Interobserver variability and ex vivo correlation were assessed. Results: Visible peritoneal tumor nodules were formed in six WAG/Rij rats within 2–4 weeks after cell injection. In most animals, tumor nodules reached a size of 4–6 mm within 3–4 weeks, with total PCI scores ranging from 10–20. The predicted PCI scores using ultrasound ranged from 11–19 and from 8–18, for observer 1 and 2, respectively, which was quite similar to the ex vivo scores. Conclusions: Ultrasound is a reliable non-invasive method to detect intraperitoneal tumor nodules and quantify tumor outgrowth in a rat model.
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DEMİRTAŞ ŞAHİN, Tuğçe, Tijen UTKAN, Ayşe KARSON, Yusufhan YAZIR et Erdal KARAOZ. « Genetik absans epilepsili WAG/Rij sıçanlarda kardiyovasküler değişiklikler : Kronik etosüksimid tedavisinin etkileri ». Cukurova Medical Journal 45, no 3 (30 septembre 2020) : 769–77. http://dx.doi.org/10.17826/cumj.724491.

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Mishra, Asht M., Xiaoxiao Bai, Joshua E. Motelow, Matthew N. DeSalvo, Nathan Danielson, Basavaraju G. Sanganahalli, Fahmeed Hyder et Hal Blumenfeld. « Increased resting functional connectivity in spike-wave epilepsy in WAG/Rij rats ». Epilepsia 54, no 7 (juillet 2013) : 1214–22. http://dx.doi.org/10.1111/epi.12227.

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Bouwman, Brigitte M., et Clementina M. van Rijn. « Effects of levetiracetam on spike and wave discharges in WAG/Rij rats ». Seizure 13, no 8 (décembre 2004) : 591–94. http://dx.doi.org/10.1016/j.seizure.2004.02.001.

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Sitnikova, Evgenia, Taras Dikanev, Dmitry Smirnov, Boris Bezruchko et Gilles van Luijtelaar. « Granger causality : Cortico-thalamic interdependencies during absence seizures in WAG/Rij rats ». Journal of Neuroscience Methods 170, no 2 (mai 2008) : 245–54. http://dx.doi.org/10.1016/j.jneumeth.2008.01.017.

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Horbach, G. J. M. Jean, Stephen K. Durham, Sing Hiem Yap et Cornelis F. A. Van Bezooijen. « Albumin elimination in female WAG/Rij rats with age : A longitudinal study ». Mechanisms of Ageing and Development 43, no 2 (mai 1988) : 137–52. http://dx.doi.org/10.1016/0047-6374(88)90042-5.

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Peeters, B. W. M. M., C. M. Rijn van, J. M. H. Vossen et A. M. L. Coenen. « Involvement of NMDA receptors in non-convulsive epilepsy in WAG/Rij rats ». Life Sciences 47, no 6 (janvier 1990) : 523–29. http://dx.doi.org/10.1016/0024-3205(90)90612-u.

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Ates, Nurbay, Deniz Sahin et Gül Ilbay. « Theophylline, a methylxanthine derivative, suppresses absence epileptic seizures in WAG/Rij rats ». Epilepsy & ; Behavior 5, no 5 (octobre 2004) : 645–48. http://dx.doi.org/10.1016/j.yebeh.2004.06.001.

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Sitnikova, Evgenia, et Gilles van Luijtelaar. « Cortical and thalamic coherence during spike–wave seizures in WAG/Rij rats ». Epilepsy Research 71, no 2-3 (octobre 2006) : 159–80. http://dx.doi.org/10.1016/j.eplepsyres.2006.06.008.

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Akman, Ozlem, Tamer Demiralp, Nurbay Ates et Filiz Yilmaz Onat. « Electroencephalographic differences between WAG/Rij and GAERS rat models of absence epilepsy ». Epilepsy Research 89, no 2-3 (mai 2010) : 185–93. http://dx.doi.org/10.1016/j.eplepsyres.2009.12.005.

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Cillino, Salvatore, Rosa Guameri, Patrizia Guarneri, Calogero Pennica, Giovanni Chichi, Federico Piccoli et Francesco Ponte. « Electroretinographic Response in WAG/Rij Rats after Low-Intensity Cyclic Light Exposure ». Ophthalmic Research 25, no 3 (1993) : 137–44. http://dx.doi.org/10.1159/000267282.

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Aygun, Hatice, Mustafa Ayyildiz et Erdal Agar. « Swimming exercise decreases the absence-like epileptic activity in WAG/Rij rats ». Behavioural Brain Research 363 (mai 2019) : 145–48. http://dx.doi.org/10.1016/j.bbr.2019.01.060.

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Coenen, A. M. L., et E. L. J. M. Van Luijtelaar. « The WAG/Rij rat model for absence epilepsy : age and sex factors ». Epilepsy Research 1, no 5 (septembre 1987) : 297–301. http://dx.doi.org/10.1016/0920-1211(87)90005-2.

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Nersesyan, Hrachya, Peter Herman, Ersan Erdogan, Fahmeed Hyder et Hal Blumenfeld. « Relative Changes in Cerebral Blood Flow and Neuronal Activity in Local Microdomains during Generalized Seizures ». Journal of Cerebral Blood Flow & ; Metabolism 24, no 9 (septembre 2004) : 1057–68. http://dx.doi.org/10.1097/01.wcb.0000131669.02027.3e.

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There is broad agreement that generalized tonic–clonic seizures (GTCS) and normal somatosensory stimulation are associated with increases in regional CBF. However, the data regarding CBF changes during absence seizures are controversial. Electrophysiologic studies in WAG/Rij rats, an established animal model of absence seizures, have shown spike-wave discharges (SWD) that are largest in the perioral somatosensory cortex while sparing the visual cortex. Recent functional magnetic resonance imaging (fMRI) studies in the same model have also shown localized increases in fMRI signals in the perioral somatosensory cortex during SWD. Because fMRI signals are only indirectly related to neuronal activity, the authors directly measured CBF and neuronal activity from specific microdomains of the WAG/Rij cortex using a specially designed probe combining laser-Doppler flowmetry and extracellular microelectrode recordings under fentanyl/haloperidol anesthesia. Using this approach, parallel increases in neuronal activity and CBF were observed during SWD in the whisker somatosensory (barrel) cortex, whereas the visual cortex showed no significant changes. For comparison, these measurements were repeated during somatosensory (whisker) stimulation, and bicuculline-induced GTCS in the same animals. Interestingly, whisker stimulation increased neuronal activity and CBF in the barrel cortex more than during SWD. During GTCS, much larger increases that included both the somatosensory and visual cortex were observed. Thus, SWD in this model produce parallel localized increases in neuronal activity and CBF with similar distribution to somatosensory stimulation, whereas GTCS produce larger and more widespread changes. The normal response to somatosensory stimulation appears to be poised between two abnormal responses produced by two physiologically different types of seizures.
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Dunaway, G. A., et T. Kasten. « Are the rat tissue/organ proportions of 6-phosphofructo-1-kinase subunits strain-specific ? » Biochemical Journal 237, no 1 (1 juillet 1986) : 157–61. http://dx.doi.org/10.1042/bj2370157.

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Recent studies suggest that the tissue/organ proportions of 6-phosphofructo-1-kinase (PFK) subunits from diverse strains of rat may be drastically different. To test this possibility rigorously, the PFK isoenzyme populations and subunit contents in muscle, liver, brain and heart were examined in the following strains: Wistar, ACI, Long Evans, Norway Brown and Wag/Rij. Regardless of the strain, adult muscle possessed only the M-type subunit; adult liver contained predominantly the L-type subunit as well as M-type and C-type subunits; and the adult brain and heart exhibited all three subunit types.
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Midzyanovskaya, I. S., G. D. Kuznetsova et L. Tuomisto. « Brain histamine in the WAG/Rij rat, an animal model of absence epilepsy ». Inflammation Research 51, S1 (avril 2002) : 49–50. http://dx.doi.org/10.1007/pl00022442.

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Velioglu, Sibel K., Oznur Gedikli, Mehmet Yıldırım et Ahmet Ayar. « Epilepsy may cause increased pain sensitivity : Evidence from absence epileptic WAG/Rij rats ». Epilepsy & ; Behavior 75 (octobre 2017) : 146–50. http://dx.doi.org/10.1016/j.yebeh.2017.07.007.

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Przewłocka, B., W. Lasoń, J. Turchan, N. de Bruin, G. van Luijtelaar, R. Przewłocki et A. Coenen. « Anatomical and functional aspects of μ opioid receptors in epileptic WAG/Rij rats ». Epilepsy Research 29, no 2 (janvier 1998) : 167–73. http://dx.doi.org/10.1016/s0920-1211(97)00081-8.

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Leo, Antonio, Carmen De Caro, Valentina Nesci, Ernesto Palma, Martina Tallarico, Michelangelo Iannone, Andrew Constanti, Giovambattista De Sarro, Emilio Russo et Rita Citraro. « Antiepileptogenic effects of Ethosuximide and Levetiracetam in WAG/Rij rats are only temporary ». Pharmacological Reports 71, no 5 (octobre 2019) : 833–38. http://dx.doi.org/10.1016/j.pharep.2019.04.017.

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ROMIJN, S., J. HENDRIKS, B. VANPUTTE, J. WEYLER, G. GUETENS, G. DEBOECKG, E. DEBRUIJN et P. VANSCHIL. « Anterograde versus retrograde isolated lung perfusion with melphalan in the WAG-Rij rat ». European Journal of Cardio-Thoracic Surgery 27, no 6 (juin 2005) : 1083–85. http://dx.doi.org/10.1016/j.ejcts.2005.02.015.

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Peeters, B. W. M. M., G. M. J. Ramakers, J. M. H. Vossen et A. M. L. Coenen. « The WAG/Rij Rat Model for Nonconvulsive Absence Epilepsy : Involvement of NonNMDA Receptors ». Brain Research Bulletin 33, no 6 (janvier 1994) : 709–13. http://dx.doi.org/10.1016/0361-9230(94)90236-4.

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