Epileptic Rat Model Research Articles

Advances on genetic rat models of epilepsy.

Considering the suitability of laboratory rats in epilepsy research, we and other groups have been developing genetic models of epilepsy in this species. After epileptic rats or seizure-susceptible rats were sporadically found in outbred stocks, the epileptic traits were usually genetically-fixed by selective breeding. So far, the absence seizure models GAERS and WAG/Rij, audiogenic seizure models GEPR-3 and GEPR-9, generalized tonic-clonic seizure models IER, NER and WER, and Canavan-disease related epileptic models TRM and SER have been established. Dissection of the genetic bases including causative genes in these epileptic rat models would be a significant step toward understanding epileptogenesis. N-ethyl-N-nitrosourea (ENU) mutagenesis provides a systematic approach which allowed us to develop two novel epileptic rat models: heat-induced seizure susceptible (Hiss) rats with an Scn1a missense mutation and autosomal dominant lateral temporal epilepsy (ADLTE) model rats with an Lgi1 missense mutation. In addition, we have established episodic ataxia type 1 (EA1) model rats with a Kcna1 missense mutation derived from the ENU-induced rat mutant stock, and identified a Cacna1a missense mutation in a N-Methyl-N-nitrosourea (MNU)-induced mutant rat strain GRY, resulting in the discovery of episodic ataxia type 2 (EA2) model rats. Thus, epileptic rat models have been established on the two paths: ‘phenotype to gene’ and ‘gene to phenotype’. In the near future, development of novel epileptic rat models will be extensively promoted by the use of sophisticated genome editing technologies.

Effects of neuropeptide Y gene transfection on seizure in rat and the expression of phosphorylated Tau protein in the rat hippocampus

Objective To discuss the effect of gene transfection of rAAV2/1-NPY- EGFP on KA-induced rat seizures, EEG and the expression of hippocampal phosphorylated Tau protein. Methods Altogether 72 healthy male Wistar adult rats were randomly divided into three groups : control group, KA group and NPY group(n=24). The epileptic models were established by the injection of KA 2 μl (0.4 μg/μl) five times to the right side of the hippocampus CA3 area every three days. rAAV2/1-NPY-EGFP group, in which 10 μl of rAAV2/1-NPY-EGFP (titer 5×1011 v. g./ml) was injected to the lateral ventricle in successful rats chronic model, while KA group was injected with an equal dose of saline. The control group was injected with an equal dose of saline both in the hippocampal CA3 area and the lateral ventricle. The seizure situation, the onset latency and EEG were observed at 2 weeks and 4 weeks after vector injection. Then the expression of phosphorylated Tau protein in hippocampus were detected with Western blotting. Results (1) Scale and latency of each seizure onset in rats of rAAV2/1-NPY-EGFP group (12.13±8.06)had no significant difference at 2 weeks(P>0.05) compared with KA group(12.10±8.07). The scale of seizure in rats of rAAV2/1-NPY-EGFP group(6.06±3.78) significantly reduced at 4 weeks(P<0.05). Latency of seizure onset (79.06±8.83min) significantly increased at 4 weeks(P<0.05), EEG epileptic discharge frequency and wave amplitude decreased (P<0.05) at 4 weeks.The control group had no seizures. (2) Compared with the control group, the expression of phosphorylated Tau protein in KA group and NPY group significantly increased(P <0.05) at 2 weeks and 4 weeks, and the expression of phosphorylated Tau protein in the NPY group (1.15±0.16 RQ value) at 4 weeks significantly decreased (P <0.05) compared with the KA group(1.87±0.23 RQ value). Conclusion rAAV2/1-NPY-EGFP gene transfection significantly reduces scale of seizure onset and prolongs latency of seizure onset in KA-induced rat model. rAAV2/1-NPY-EGFP gene transfection may play anti-epileptic and neuroprotective effects through inhibiting the expression of phosphorylated Tau protein in hippocampus of KA-induced epileptic rat model. Key words: Neuropeptide Y; Epilepsy; Gene transfection; Phosphorylated Tau protein

Functional recovery and neuronal regeneration of a rat model of epilepsy by transplantation of Hes1-down regulated bone marrow stromal cells

Gamma-amino butyric acid (GABA)ergic cells play an important inhibitory role in epilepsy. Until now, there are no reports on promoting transplanted bone marrow stromal cells (BMSCs) to differentiate into GABAergic cells for treatment of epilepsy. In this study, hairy and enhancer of split 1 (Hes1)-down regulated BMSCs (H-BMSCs) were transplanted into an epileptic rat model to induce GABAergic cells differentiation to improve the function recovery and neuronal regeneration. First, Hes1 expression in isolated BMSCs was down regulated by Hes1 siRNA. Then, the H-BMSCs were labeled with 5-bromo-2′-deoxyuridine (BrdU) and transplanted into the lateral ventricle of pilocarpine-induced epileptic rats. To evaluate the therapeutic effects, behavior and electroencephalography (EEG) of the recipient rats were monitored in the following 4weeks, followed by histological confirmation. The results showed that the rate of mortality, frequency of spontaneous recurrent seizures (SRS) and incidence of epileptiform waves presented a tendency to decrease after H-BMSCs transplantation. The histology results showed that (1) the transplanted H-BMSCs which migrated to the adjacent parahippocampal cortical areas expressed glutamate decarboxylase (GAD) 67, neuron-specific enolase (NSE) and some glial fibrillary acidic protein (GFAP), and (2) the neuronal density of corresponding cortical areas was significantly increased (P<0.01 VS. experimental group I or positive control group). Given these results and other advantages of BMSCs, such as easy harvest and minimal immunogenicity, transplantation of H-BMSCs could be a promising approach to improve the functional recovery and neuronal regeneration of epileptic model in the early stage.

Scorpion ethanol extract and valproic acid effects on hippocampal glial fibrillary acidic protein expression in a rat model of chronic-kindling epilepsy induced by lithium chloride-pilocarpine.

The present study analyzed the effects of ethanol extracts of scorpion on epilepsy prevention and hippocampal expression of glial fibrillary acidic protein in a lithium chloride-pilocarpine epileptic rat model. Results were subsequently compared with valproic acid. Results showed gradually-increased hippocampal glial fibrillary acidic protein expression following model establishment; glial fibrillary acidic protein mRNA expression was significantly increased at 3 days, reached a peak at 7 days, and then gradually decreased thereafter. Ethanol extracts of scorpion doses of 580 and 1 160 mg/kg, as well as 120 mg/kg valproic acid, led to a decreased number of glial fibrillary acidic protein-positive cells and glial fibrillary acidic protein mRNA expression, as well as decreased seizure grades and frequency of spontaneously recurrent seizures. The effects of 1 160 mg/kg ethanol extracts of scorpion were equal to those of 120 mg/kg valproic acid. These results suggested that the anti-epileptic effect of ethanol extracts of scorpion were associated with decreased hippocampal glial fibrillary acidic protein expression in a rat model of lithium chloride-pilocarpine induced epilepsy.

Increased expression of histone deacetylases 2 in temporal lobe epilepsy: A study of epileptic patients and rat models

Histone deacetylases 2 (HDAC2) is expressed in the central nervous system; it has multiple functions in neural plasticity. However, we do not know if HDAC2 is also involved in the pathology of epilepsy. Here we report that HDAC2 was expressed in the brain tissues of both control and temporal lobe epilepsy (TLE) patients. Results from immunofluorescence and immunohistochemistry showed that HDAC2 was primarily located in the nucleus and that TLE patients exhibit significantly more HDAC2 positive cells than control. Western blotting showed that HDAC2 protein levels were significantly higher in TLE than in control brain. Moreover, in the rat model of TLE, there was a sustained enhancement of HDAC2 expression in rat models of TLE. HDAC2 was significantly increased in both the acute (1 day) and chronic (60 days) animals compared with control group. These results suggest that HDAC2 play an important role in the pathogenesis of human TLE.

Up-regulation of apelin in brain tissue of patients with epilepsy and an epileptic rat model

Prolonged epileptic seizures or SE can cause neuronal cell death. However, the exact role of neuroprotectant against brain injury during epileptic seizure needs to be further elucidated. The aim of this study was to investigate the expression of the apelin, a novel neuroprotective peptide, in brain tissues of the patients with temporal lobe epilepsy (TLE) and experimental rats using immunohistochemistry, immunofluorescence and Western blotting analysis and to discuss the possible role of apelin in TLE. Thirty temporal neocortical tissue samples from the patients with drug-refractory TLE underwent surgical therapy and nine histologically normal temporal lobes tissues as controls were used in our study. Fifty-six Sprague–Dawley rats were randomly divided into seven groups, including one control group and six groups with epilepsy induced by lithium–pilocarpine. Hippocampus and adjacent cortex were taken from the controls and epileptic rats at 1, 3, 7, 14, 30, and 60 days after onset of seizures. Apelin was mainly expressed in the neurons of TLE patients and controls, and was significantly increased in TLE patients compared with the controls. Apelin was also expressed in the neurons of experimental and control rats, it was gradually increased in the experimental rat post-seizure and reached a stable high level in chronic epileptic phase. Our results demonstrated that the increased expression of apelin in the brain may be involved in human TLE.

Closed-loop seizure control on epileptic rat models

In this paper numerous alternative treatments in addition to pharmacological therapy are proposed for their use in epileptic patients. Epileptic animal models can play a crucial role in the performance evaluation of new therapeutic techniques. The objective of this research is to first develop various epileptic rat models; second, develop a portable wireless closed-loop seizure controller including on-line seizure detection and real-time electrical stimulation for seizure elimination; and third, apply the developed seizure controller to the animal models to perform on-line seizure elimination. The closed-loop seizure controller was applied to three Long-Evans rats with spontaneous spike–wave discharges (non-convulsive) and three Long-Evans rats with epileptiform activities induced by pentylenetetrazol (PTZ) injection (convulsive) for evaluation. The seizure detection accuracy is greater than 92% (up to 99%), and averaged seizure detection latency is less than 0.6 s for both spontaneous non-convulsive and PTZ-induced convulsive seizures. The average false stimulation rate is 3.1%. Near 30% of PTZ-induced convulsive seizures need more than two times of 0.5 s electrical stimulation for suppression and 90% of the non-convulsive seizures can be suppressed by only one 0.5 s electrical stimulation.

Effect of intracranial administration of ethosuximide in rats with spontaneous or pentylenetetrazol-induced spike-wave discharges

Generalized absence seizures are characterized by bilateral spike-wave discharges (SWDs), particularly in the frontoparietal cortical region. In WAG/Rij and GAERS rats with absence epilepsy, recent evidence indicates that SWDs arise first from the lateral somatosensory cortex (LSC), that is, the cortical focus theory. To further understand the cortical role in SWD generation, two epileptic rat models were assessed. Two models, Long-Evans rats with spontaneous SWDs and Wistar rats with low-dose pentylenetetrazol-induced SWDs (20 mg/kg, i.p.), were administered intracortical or intrathalamic ethosuximide (ESM) or saline. Electroencephalographic recordings were analyzed before and after intracranial microinfusion to evaluate onset, frequency, and duration of SWDs. In both epileptic rat models, ESM in the LSC significantly reduced SWD number, shortened SWD duration, and delayed SWD onset compared to saline. By contrast, ESM in the medial somatosensory cortex had little effect compared to saline. Intrathalamic infusion of ESM only delayed SWD onset. These findings suggest that the LSC may be essential for the occurrence of SWDs. Our data support the cortical focus theory for the generation of absence seizures.

Comparison of MMP-9 activation in different absence epileptic rat models: brain zymography study

Event Abstract Back to Event Comparison of MMP-9 activation in different absence epileptic rat models: brain zymography study E. Szodorai1*, E. Takács1, Z. Kovács2, A. K. Kékesi3, A. Czurkó1 and G. Juhász1 1 Eötvös Lorand University, Institute of Biology, Hungary 2 University of West Hungary, Department of Zoology, Hungary 3 Eötvös Lorand University, Department of Physiology and Neurobiology, Hungary There are two widely used genetic models of absence epilepsy: the GAERS strain is a selected strain from Wistars and the WAG/Rij strain is a selected single rat pair origin strain. The question is as follows: Are the two strains identical in terms of molecular mechanisms of seizure genesis? MMP-9 is an inducible metalloproteinase locating in the synapses and its role is the molecular tuning of synaptic transmission via protein degradation. In the present study we compared parietal and prefrontal cortices and the thalamus as well as hippocampus of 4 NEC, 4 GAERS, 4 WAG/Rij rats applying brain tissue zymography that showed the changes of pro-MMP-9, active-MMP-9 and MMP-2. We did not observed any changes in MMP-2 indicating the accuracy of protein quantification. In WAG/Rij rats we found higher level of active-MMP-9 in the cortical structures and also elevated pro-MMP-9 level in the thalamus and the cortex. Since the number of seizures is lower in WAG/Rij rats than in GAERS, we suggest that the elevated MMP activation in the cortical genesis sites of seizures could modulate the seizure genesis in WAG/Rij rats but not in GAERS. Our suggestion is supported by the fact that inhibiting MMP-9 activation by doxycycline in WAG/Rij rats increases the number of seizures. Thus we claim that significant differences can be in the molecular mechanisms of seizure genesis of the two strains developed by different selection methods. Keywords: disorders, Neuroscience Conference: 13th Conference of the Hungarian Neuroscience Society (MITT), Budapest, Hungary, 20 Jan - 22 Jan, 2011. Presentation Type: Abstract Topic: Disorders Citation: Szodorai E, Takács E, Kovács Z, Kékesi AK, Czurkó A and Juhász G (2011). Comparison of MMP-9 activation in different absence epileptic rat models: brain zymography study. Front. Neurosci. Conference Abstract: 13th Conference of the Hungarian Neuroscience Society (MITT). doi: 10.3389/conf.fnins.2011.84.00047 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 03 Mar 2011; Published Online: 23 Mar 2011. * Correspondence: Dr. E. Szodorai, Eötvös Lorand University, Institute of Biology, Budapest, Hungary, editszodorai@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers E. Szodorai E. Takács Z. Kovács A. K Kékesi A. Czurkó G. Juhász Google E. Szodorai E. Takács Z. Kovács A. K Kékesi A. Czurkó G. Juhász Google Scholar E. Szodorai E. Takács Z. Kovács A. K Kékesi A. Czurkó G. Juhász PubMed E. Szodorai E. Takács Z. Kovács A. K Kékesi A. Czurkó G. Juhász Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Protective effect of curcumin against seizures and cognitive impairment in a pentylenetetrazole-kindled epileptic rat model

Aim Epilepsy as well as chronic use of most antiepileptic drugs predisposes to cognitive impairment. Curcumin has been reported to possess antioxidant, anticonvulsant as well as neuroprotective potential. Hence, this study was conducted to evaluate the effect of curcumin against seizures, cognitive impairment and oxidative stress in pentylenetetrazole-induced kindling in rats. Main methods The effect of pretreatment with curcumin (100, 200 and 300 mg/kg, orally) on pentylenetetrazole (PTZ)-induced kindling, kindling-induced cognitive impairment and oxidative stress was evaluated. Male Wistar rats were injected PTZ (30 mg/kg, i.p.) once every alternate day (48 ± 1 h) until the development of kindling. Cognitive impairment was assessed using elevated plus maze and passive avoidance test while the oxidative stress parameters (malondialdehyde and glutathione) were estimated in the whole brain at the end of experiments. Key findings PTZ, 30 mg/kg, induced kindling in rats after 31.0 ± 1.4 days. Curcumin showed dose-dependent anti-seizure effect. Curcumin (300 mg/kg) significantly increased the latency to myoclonic jerks, clonic seizures as well as generalized tonic–clonic seizures, improved the seizure score and decreased the number of myoclonic jerks. PTZ kindling induced a significant oxidative stress and cognitive impairment which was reversed by pretreatment with curcumin in a dose-dependent manner. Significance The results indicate that pretreatment with curcumin ameliorates seizures, oxidative stress and cognitive impairment in PTZ induced kindling in rats. These results thus suggest the potential of curcumin as an adjuvant in epilepsy both to prevent seizures as well as to protect against seizure induced memory impairment.

Effects of ganoderma lucidum spores on expression of PSA‐NCAM and hippocampus mossy fiber sprouting in pentylenetetrazol‐induced epileptic rats

The present study was undertaken to investigate the effects of ganoderma lucidum spores (GLS) on expression of polysialic acid neural cell adhesion molecule (PSA‐NCAM) and hippocampus mossy fiber sprouting (MFS) in pentylenetetrazol (PTZ)‐induced epileptic rat model. Thirty male Sprague‐Dawley rats (180–220g) were divided into three groups: control, GLS and epilepsy model groups. The results showed that, compared with epilepsy model groups, the rats of GLS group have longer latent periods, and lower seizure level. Their seizure durations also were shorter than epilepsy model group. In the granular cell layer of dentate gyrus and stratum pyramidal and stratum oriens of the CA3 region, epilepsy model group have more PSA‐NCAM than GLS group and control group; compared with epilepsy model group, MFS in the granular cell layer of dentate gyrus were obviously less in GLS group, and no statistically significant difference was detected when compared with control group; in the stratum pyramidal and stratum oriens of the CA3 region, MFS in GLS group was less than epilepsy model group, but obviously more than control group.ConclusionFor PTZ induced epileptic rats, there were different severities of MFS in different regions of hippocampus. GLS can decrease expression of PSA‐NCAM and MFS effectively, and that might be one of its mechanism of lighten rats′ seizure induced by PTZ.

Metabolic changes in temporal lobe structures measured by HR-MAS NMR at early stage of electrogenic rat epilepsy

The purpose of this study was to determine cerebral metabolic profile changes in response to electric stimulation to the right dorsal hippocampus (HPC) for the establishment of an epileptic rat model. Electroencephalogram measurements and behavioral results indicated that the experimental rats were in an early stage of epilepsy. Metabolites were determined by high-resolution magic-angle-spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy of the following intact brain tissue: bilateral hippocampi, entorhinal cortices (ECs), and temporal lobes (TLs). The NMR data was statistically analyzed using principal component analysis (PCA). Results demonstrated that metabolic profiles were significantly different between the experimental and sham rats in the bilateral hippocampi and the ipsilateral EC. Significant increases in total creatine in the ipsilateral HPC and alanine in the ipsilateral TL were measured ( p < 0.05). Some metabolite levels were disturbed in the bilateral HPC-EC loops. In the sham group, glutamate and choline concentrations were significantly higher or lower in the ipsilateral EC than bilateral hippocampi, respectively ( p < 0.01). However, such differences were not observed in the experimental group. In addition, N-acetylaspartate levels in the experimental group were significantly less in the ipsilateral HPC than in bilateral ECs ( p < 0.05). The level of myo-inositol in the ipsilateral EC significantly increased in the experimental group, compared to the contralateral EC ( p < 0.05). These results may provide metabolic information about temporal lobe structures to provide more knowledge about epileptic abnormalities at the early stage.

Suppression of penicillin-induced epileptiform activity by Nigella sativa: Possible mediation by neurotransmitters

Nigella sativa (NS), an endogenous plant of family Ranunculaceae, exhibits a wide range of biological activity. This report explores the effect of aqueous extract of NS seeds on penicillin-(PCN-100 IU in 100 μl) induced epileptic rat model. Oral pretreatment of NS (250 mg/kg) suppressed PCN-induced seizure considerably, reduced spike-wave discharges and occurrence of generalized tonic–clonic seizures. Electroencephalographic data showed NS pretreatment to experimental animals elicited 85% abolition of high voltage spike discharges. NS pretreatment resulted in elevation of serotonin (5-HT) level and decreased dopamine (DA) level in cerebral cortex (CC), cerebellum (CB), caudate nucleus (CN) and midbrain (MB). A significant decrease in norepinephrine (NE) level was observed only in the CC. The present study suggests that chronic administration of NS protects PCN-induced generalized epilepsy by selectively altering the monoamine level in different brain regions. The seizure abolition observed in the NS pretreated rats was comparable to the anticonvulsive pattern exhibited by diazepam. The results suggest that NS has promising anticonvulsant action.

Presubiculum StimulationIn VivoEvokes Distinct Oscillations in Superficial and Deep Entorhinal Cortex Layers in Chronic Epileptic Rats

The characteristic cell loss in layer III of the medial entorhinal area (MEA-III) in human mesial temporal lobe epilepsy is reproduced in the rat kainate model of the disease. To understand how this cell loss affects the functional properties of the MEA, we investigated whether projections from the presubiculum (prS), providing a main input to the MEA-III, are altered in this epileptic rat model. Injections of an anterograde tracer in the prS revealed bilateral projection fibers mainly to the MEA-III in both control and chronic epileptic rats. We further examined the prS-MEA circuitry using a 16-channel electrode probe covering the MEA in anesthetized control and chronic epileptic rats. With a second 16-channel probe, we recorded signals in the hippocampus. Current source density analysis indicated that, after prS double-pulse stimulation, afterdischarges in the form of oscillations (20-45 Hz) occurred that were confined to the superficial layers of the MEA in all epileptic rats displaying MEA-III neuronal loss. Slower oscillations (theta range) were occasionally observed in the deep MEA layers and the dentate gyrus. This kind of oscillation was never observed in control rats. We conclude that dynamical changes occur in an extensive network within the temporal lobe in epileptic rats, manifested as different kinds of oscillations, the characteristics of which depend on local properties of particular subareas. These findings emphasize the significance of the entorhinal cortex in temporal lobe epilepsy and suggest that the superficial cell layers could play an important role in distributing oscillatory activity.

Validation of a method for localised microinjection of drugs into thalamic subregions in rats for epilepsy pharmacological studies

Objectives: To validate a method for the chronic implantation of micro-cannulae to examine the effect of drug administration to two small brain regions critical to the control of generalised seizures, the reticular nucleus of the thalamus (Rt) and the ventrobasal thalamus (VB), in a genetically epileptic rat model. Method: Micro-cannulae guides (length 9 mm, 26 G, i.d. 0.24 mm, o.d. 0.46 mm) were implanted bilaterally into either the Rt or the VB of 11- to 13-week-old Genetic Absence Epilepsy Rats from Strasbourg (GAERS) using a stereotaxic head frame. After a seven-day recovery period the animals were injected with 0.2 μl of methylene blue. The animals were allowed to move freely in their cages for a further 90 min while a post-drug EEG recording was acquired and then brains were perfused with 4% paraformaldehyde and extracted. Twenty-micrometer slices were cut on a cryostat and the site and extent of the methylene blue staining in the brain determined. The implantation co-ordinates were adjusted accordingly, and then a validation study was performed on a further cohort of rats ( n = 8 Rt, n = 7 VB). Results: The co-ordinates that were found to most accurately localise the Rt were: AP −3 mm, ML 3.6 mm, DV −5.8 mm (relative to Bregma). Those that accurately localised the VB were: AP −3 mm, ML 2.6 mm, DV −5.5 mm. In the validation study, the dye staining was measured to diffuse an average radius of 520 ± 120 μm from the centre of the injection site for the 0.2 μl injection in both brain hemispheres. For the VB injections the dye remained confined within the structure, however, for the smaller Rt there was spread to surrounding structures in the axial plane. The radial diffusion for the 0.5 μl injection was similar, but more of the dye was found to spread back up the cannula tract away from the target zone. Conclusion: These studies have validated a method for accurate and localised injection of drugs into the VB and Rt for neuropharmacological studies in a rat model of generalised epilepsy. This method allows the measurement of localised drug effects on EEG and generalised seizure activity at these sites.

Texture analysis of the brain: from animal models to human applications

Magnetic resonance imaging (MRI) is widely used to image brain in vivo both in studies in animal models and for human diagnosis. A large part of the value of MRI is due to the fact that soft tissue contrast is enhanced by the substantial variation in the T(1) and T(2) relaxation times between tissues. It may be possible to use an alternative approach, which does not rely on the absolute measurement of relaxation times. Generally speaking, textures are complex visual patterns composed of entities, or subpatterns, that have characteristic brightness, color, slope, size, etc. Thus, texture can be regarded as a similarity grouping in an image. The properties of the local subpattern give rise to the perceived lightness, uniformity, density, roughness, regularity, linearity, frequency, phase, directionality, coarseness, randomness, fineness, smoothness, and granulation. The purpose here is to illustrate how texture analysis can be used in animal models and in human clinical applications, as well as in the search for further pharmacological applications in humans. Thus, this article summarzes three different MRI studies in (i) rats, using the lipocarpine epileptic rat model as an animal model; (ii) patients with Alzheimer's disease; and (iii) patients with schizophrenia.

Contribution of intralaminar thalamic nuclei to spike-and-wave-discharges during spontaneous seizures in a genetic rat model of absence epilepsy.

In an epileptic rat model of generalized absence epilepsies, the genetic absence epilepsy rats from Strasbourg (GAERS), simultaneous recordings of bilateral epidural electroencephalogram (EEG) of the prefrontal cortex and unit activity of neurons in the intralaminar centrolateral (CL) and paracentral thalamic nucleus (PC) were performed under neurolept-anaesthesia (fentanyl-dehydrobenzperidol analgesia). Spike-and-wave (SW) seizures in these rats are characterized by generalized 7-10 Hz spike-and-wave discharges (SWDs) on the EEG. All neurons recorded in intralaminar thalamic nuclei during spontaneous SWDs showed high-frequency (average 368 Hz, range 200-500 Hz), burst-like activity, which occurred in a highly synchronized fashion with every SWD or with alternating SWD-complexes. Burst discharges in intralaminar neurons were delayed by 13.1 ms (CL) and 12.7 ms (PC), with respect to the spike component of a given SWD on the EEG, whereas burst discharges in the ventrobasal thalamus (VB) and in the rostral nucleus reticularis thalami (rRT) preceded the spike component by 17.8 ms and 8.3 ms, respectively. The onset of SWDs on the EEG was preceded by a tonic firing pattern (20-50 Hz) in about one third of CL and PC neurons. Microiontophoretic application of the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline aggravated, whereas, the glutamate receptor antagonists DNQX and APV dampened, SWD-related discharges in PC and CL; the GABAB receptor antagonist CGP 35347 had no measurable effect. These data indicate that intrathalamic nuclei are recruited rhythmically during SWDs, through mechanisms that seem to rely on a delayed glutamatergic excitation modulated by GABAergic influences, rather than a GABA-mediated rebound burst activity typical of relay cells. The finding of a temporal delay of SWD-related activity in intrathalamic, compared with "specific" thalamic relay nuclei, does not support the notion of a leading or pacemaker role in SWD generation. It is, however, rather suggestive of a function of intrathalamic neurons during synchronization and maintenance of neuronal oscillations, and these intrathalamic neurons may be recruited through glutamatergic corticofugal inputs.