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Biomedical subjects

R Demir

Publications and source records attributed to R Demir.

At least 19 recordsLinked to original sources
PubMed2006

Immunolocalizations of VEGF, its receptors flt-1, KDR and TGF-beta's in epithelial ovarian tumors.

OBJECTIVE: Angiogenesis is an essential factor for growth, differentiation, invasion and metastasis of tumors. In this study, we aimed to evaluate the immunolocalizations of vascular endothelial growth factor (VEGF), its receptors flt-1, KDR/flk-1, and transforming growth factor-beta's (TGF-beta) in epithelial ovarian tumors, utilizing indirect immunohistochemistry to understand the role of the angiogenic events in ovarian neoplasia. METHODS: Tissue blocks from 40 patients who had ovarian pathology (borderline serous-mucinous tumor and malignant serous-mucinous adenocarcinoma of the ovary) were included in this study. All formalin-fixed, paraffin-embedded tissue sections were stained with hematoxylin-eosin or primary antibodies against VEGF, flt-1, KDR/flk-1, TGF-beta1, TGF-beta2 and TGF-beta3 using the avidin-biotin-peroxidase method. H-SCORE, a semi-quantitative grading system, was used to compare immunohistochemical staining intensities. RESULTS: Positive VEGF immunoreactivity was concentrated in the epithelial and stromal parts of all the ovarian samples and the endothelial cells in the stroma were also stained. Increased immunoreactivity of VEGF was observed in malignant ovarian adenocarcinomas compared to the borderline tumors of the ovary. VEGF receptors, flt-1 and KDR/flk-1 immunoreactivities were detected not only in vascular endothelial cells, but also in tumor cells at malignant sites. Immunoreactivities of VEGF and its receptors were coexpressed in tumor cells of the ovarian carcinoma. While immunoreactivities of TGF-beta1 and TGF-beta2 were both overexpressed in malignant ovarian carcinomas, immunoreactivity of TGF-beta3 was still mild. CONCLUSION: Our results suggest that overexpression of VEGF, its receptors flt-1, KDR/flk-1 and TGF-beta interaction may play an important role in the ovarian cancer biology, with potential effects on tumor growth and angiogenesis. New therapeutic strategies using VEGF and TGF-beta antagonists could obtain an additional approach to the treatment ovarian carcinoma by inhibiting angiogenesis.

Adult↗
PubMed2005

Sequential steps during vasculogenesis and angiogenesis in the very early human placenta.

Development of blood vessels takes place via two subsequent processes, vasculogenesis and angiogenesis. During vasculogenesis, formation of first blood vessels is achieved by differentiation of hemangiogenic stem cells from pluripotent mesenchymal cells, while during angiogenesis new blood vessels form from already existing vessels. The combination of our data with those from the literature leads us to depict the chronological steps of cell differentiation in the mesenchymal core of placental villi during vasculogenesis and angiogenesis. This current opinion will focus on the temporal and spatial expression of VEGF and its receptors VEGFR-1 and VEGFR-2, and the angiopoietin receptors Tie-1 and Tie-2 in parallel to vascular maturation in human placental villi during very early stages of placental development. There is evidence that the interplay of a variety of growth factors secreted from different cell types during development is needed to trigger as well as maintain placental vasculogenesis and angiogenesis.

Adult↗
PubMed2005

Spatial and temporal distribution of Tie-1 and Tie-2 during very early development of the human placenta.

Vasculogenesis in the human placenta comprises differentiation and growth of newly forming blood vessels derived from hemangiogenic stem cells within the mesenchymal core of villi. In a second stage, angiogenesis leads to the expansion and remodeling of the already existing vessels. At present, relatively little is known about the regulatory mechanisms of vasculogenesis and angiogenesis during very early placentation. Using placental villous tissues from days 22 to 48 of pregnancy, we analyzed the spatial and temporal expression of Tie-1 and Tie-2 in parallel to vascular maturation in the human placenta. In immunohistochemistry both receptors, Tie-1 and Tie-2 show a cell and villous type specific expression during this early phase of placental development. Especially, cytotrophoblast and hemangiogenic cell cords in mesenchymal villi and Hofbauer cells in immature intermediate villi have the strongest immunoreactivities. Western blot analysis showed that no significant changes were detected for Tie-1 and Tie-2 as pregnancy advanced. Moreover, phospho-Tie-2 levels did not change significantly in parallel to pregnancy ages. We conclude that both receptors are involved in angiogenesis as well as vascular modulation of early vessels. Due to their spatial distribution we speculate on an additional role in regulation of villous and extravillous trophoblastic behavior.

Adult↗
PubMed2004

Sequential expression of VEGF and its receptors in human placental villi during very early pregnancy: differences between placental vasculogenesis and angiogenesis.

Vascularization within the human placenta is the result of the de novo formation of vessels derived from pluripotent precursor cells in the mesenchymal core of the villi. Vascularization of placental villi starts at around day 21 post conception (p.c.) with a four somite embryo. At this stage progenitors of haemangiogenic cells differentiate to form first vessels. These progenitor cells are thought to be directly derived from mesenchymal cells rather than originating from fetal blood cells. We investigated the relation between differentiation of stromal cells towards endothelial cells and vascular structures and the expression pattern of the respective growth factors. Using transmission electron microscopy and immunohistochemistry (for VEGF, Flt-1, Flk-1, CD14, CD34, and CD68) the development of placental vasculogenesis during very early stages of pregnancy (days 22-48 p.c.) was studied. We found that VEGF is strongly expressed in villous cytotrophoblast cells and subsequently in Hofbauer cells while its receptors Flt-1 and Flk-1 are found on vasculogenic and angiogenic precursor cells. The developmental expression and secretion of VEGF suggests its involvement in recruitment, maintenance and formation of first angiogenic cells and vessels. Interactions between VEGF and Flk-1 and Flt-1 may regulate placental vasculogenesis and angiogenesis in a paracrine and autocrine manner. The sequential expression of growth factors in different cell types may point to the fact that placental vasculogenesis and angiogenesis are clearly distinct events.

Antigens, CD↗
PubMed2004

Immunocytochemical detection of synaptophysin in enteric neurones during prenatal development in the rat stomach.

Summary In this study, the localization and appearance of synaptophysin-immunoreactive (IR) nerve cells and their relationships with the developing gastric layers were studied by immunocytochemistry and light microscopy in the embryonic rat stomach. The stomachs of Wistar rat embryos aged 13-21 days were used. The first neuronal bodies and their processes containing synaptophysin-immunoreactivity were observed on embryonic day 13. In contrast, synaptophysin-IR nerve terminals were first observed between mesenchymal cells on embryonic day 14. These results indicate that synaptophysin is expressed in growing neurits and neuronal cell bodies before these neurones have established synaptic connections. The occurrences of mesenchymal cell condensation near synaptophysin-IR neuroblasts on embryonic day 15 reflect an active nerve element-specific mesenchymal cell induction resulting in the morphogenesis of muscle cells. Similarly, the appearance of glandular structures after synaptophysin-IR neuroblasts, on embryonic day 18, suggests that the epithelial differentiation may be closely related to the neuronal maturation as well as other factors. Finally, synaptophysin is functionally important in neuronal development and maturation, together with the establishment of neuroneuronal and neuromuscular contacts and in epithelial differentiation.

Animals↗
PubMed2003

The effect of testosterone on gastrocnemius muscle fibres in growing and adult male and female rats: a histochemical, morphometric and ultrastructural study.

In this study, the effect of testosterone on gastrocnemius muscle fibres in growing and adult rats (male and female) was examined using histochemical, morphometric and ultrastructural techniques. After physiological saline (PS), olive oil (OvO) or olive oil + testosterone (OvOT) injections on 72 rats (growing and mature, 36 male and 36 female), the sample tissues of fibre types of the gastrocnemius muscle taken were examined by histochemical [alkaline adenosine triphosphatase (alk-ATPase), acid ATPase (ac-ATPase)], morphometric and ultrastructural techniques. In PS-injected control groups, the gastrocnemius muscle of both sexes contained all the fibre types studied [slow-oxidative muscle fibres (type I), fast-oxidative glycolytic muscle fibres (type IIA) and fast-glycolytic muscle fibres (type IIB)]. The type I fibres had the smallest diameter, type IIA had a medium diameter and type IIB fibres had the largest diameter. In OvO-injected groups, it was observed that the OvO had little effect on the gastrocnemius muscles of either sex, although there was significant enlargement of type IIB fibres. After the injection of OvOT, hypertrophy of muscle fibres was determined by morphometric study. The biggest increase in diameter was on type I fibres. In addition, degenerations on some mitochondria, accumulation of lipid droplets on type I and type II fibres, an increase in glycogen particles, bifurcation of myofibrils, an increase in the number and diameter of units resembling T tubules and an increase in ribosomal content were also observed in the same group by transmission electron microscope. Consequently, it was determined that testosterone can induce protein synthesis in gastrocnemius muscle fibres, and induces changes in shape and size, and also can change the appearance and the number of fibres.

Aging↗
PubMed2003

The zonal distributions of alkaline phosphatase, adenosine triphosphatase, laminin, fibronectin and chondroitin 4-sulphate in growing rat humerus proximal epiphyseal cartilage: a histochemical and an immunohistochemical study.

Although there are many studies about epiphyseal cartilage extracellular matrix (ECM) macromolecules in bone formation, studies of their distribution and role in the mineralization of these components in growing rat humerus proximal epiphyseal cartilage have not been sufficiently detailed. The aim of this study was to determine the distributions of alkaline phosphatase (ALP), adenosine triphosphatase (ATPase), laminin, fibronectin and chondroitin 4-sulphate in growing rat humerus proximal epiphyseal cartilage. The rats were killed by cervical dislocation, and the humeri were removed, sectioned (6 and 10 microm) on a cryotome or paraffin microtome, and stained using histochemical and immunohistochemical methods. ALP and ATPase were markedly observed in the hypertrophy and calcifying cartilage. In addition, ATPase was found to be very strongly positive in the tangential zone of articular cartilage. Results of immunohistochemical staining for laminin, fibronectin and chondroitin 4-sulphate showed that the immunostaining was the heaviest in the tangential zone of articular cartilage. In growing epiphyseal plates, there were differences in the density of these macromolecules of chondrocytes as a function of the maturation process. In conclusion, these ECM macromolecules of epiphyseal cartilage may regulate the cell-cell and cell-matrix interactions as well as the matrix calcification during the ossification of epiphyseal cartilage.

Adenosine Triphosphatases↗
PubMed2003

Expression of insulin, insulin-like growth factor I and glucocorticoid receptor in rat uterus and embryo during decidualization, implantation and organogenesis.

The significance of insulin, insulin-like growth factor I (IGF-I) and glucocorticoids to the early mammalian embryo is clear in that they are key regulators of both mitogenic and metabolic effects during development. In the present study, the temporal sequence of expression of the respective receptor proteins was investigated for the first time in the developing rat utero-embryonic unit between conception and day 12 of gestation using immunocytochemistry. Insulin, IGF-I and glucocorticoid receptor were expressed in embryonic tissues after the start of implantation, and were co-localized in the primary ectoderm, extraembryonic ectoderm as well as in the ectoplacental cone. The parietal endoderm was devoid of glucocorticoid receptor staining, whereas IGF-I receptor was absent in visceral endoderm. After completion of basic organogenesis, the neural tube, notochord, otic placode, Wolffian duct, mesonephros and intestinal tube expressed insulin, IGF-I and glucocorticoid receptor. The glucocorticoid receptor was not expressed in heart tube and dorsal aortae. Considerable amounts of insulin receptor were detected in trophoblast-derived giant cells. In the uterus, luminal epithelium, endometrial stromal and myometrial smooth muscle cells immunoreacted with antisera against insulin, IGF-I and glucocorticoid receptor. Endometrial glands remained negative for the glucocorticoid receptor throughout the gestational period investigated. Uterine hormone receptor expression reached a peak at days 4 and 5 of gestation in endometrial stromal cells and decidua, respectively. In conclusion, the demonstrated ontogenetic pattern of insulin, IGF-I and glucocorticoid receptor expression indicates the potential sites of biological action of the respective ligands, providing supportive evidence for their critical importance during the course of embryogenesis in rats.

Animals↗
PubMed2001

Glucose transporter expression in rat embryo and uterus during decidualization, implantation, and early postimplantation.

Efficient transfer of glucose from the mother to the embryonic compartment is crucial to sustain the survival and normal development of the embryo in utero, because the embryo's production of this primary substrate for oxidative metabolism is minimal. In the present study, the temporal sequence of expression of the sodium-independent facilitative glucose transporter isoforms GLUTs 1, 3, 4, and 5 was investigated in the developing rat uteroembryonic unit between conception and Gestational Day 8 using immunohistochemistry. The GLUTs 1, 3, and 4 were expressed in the embryonic tissues after the start of implantation, being colocalized in the parietal endoderm, visceral endoderm, primary ectoderm, extraembryonic ectoderm, and the ectoplacental cone. In the uterus, a faint GLUT1 labeling emerged, but not until Gestational Day 3, in the luminal epithelium, endometrial stroma, and decidual cells. The intensity of GLUT1 staining increased in the latter population with progressing decidualization. Endometrial glands and myometrial smooth muscle cells stained neither for GLUT1 nor for GLUT3 until postimplantation. During all developmental stages examined, GLUT4 was visualized throughout the pregnant rat uterus, as was GLUT3 (with the above-mentioned exceptions). The density of GLUT5 was generally less than the sensitivity of the immunohistochemical detection method in all tissues investigated. In conclusion, the data point to a significant expression of the high-affinity glucose transporters GLUTs 1, 3, and 4 in the rat uteroembryonic unit, providing supportive evidence for an important role of facilitative glucose diffusion during peri-implantation development.

Animals↗
PubMed2001

Epileptiform discharges with in-vivo-like features in slices of rat piriform cortex with longitudinal association fibers.

Brain slices serve as useful models for the investigation of epilepsy. However, the preparation of brain slices disrupts circuitry and severs axons, thus complicating efforts to relate epileptiform activity in vitro to seizure activity in vivo. This issue is relevant to studies in transverse slices of the piriform cortex (PC), the preparation of which disrupts extensive rostrocaudal fiber systems. In these slices, epileptiform discharges propagate slowly and in a wavelike manner, whereas such discharges in vivo propagate more rapidly and jump abruptly between layers. The objective of the present study was to identify fiber systems responsible for these differences. PC slices were prepared by cutting along three different nearly orthogonal planes (transverse, parasagittal, and longitudinal), and epileptiform discharges were imaged with a voltage-sensitive fluorescent dye. Interictal-like epileptiform activity was enabled by either a kindling-like induction process or disinhibition with bicuculline. The pattern of discharge onset was very similar in slices cut in different planes. As described previously in transverse PC slices, discharges were initiated in the endopiriform nucleus (En) and adjoining regions in a two-stage process, starting with low-amplitude "plateau activity" at one site and leading to an accelerating depolarization and discharge onset at another nearby site. The similar pattern of onset in slices of various orientations indicates that the local circuitry and neuronal properties in and around the En, rather than long-range fibers, assume dominant roles in the initiation of epileptiform activity. Subtle variations in the onset site indicate that interneurons can fine tune the site of discharge onset. In contrast to the mode of onset, discharge propagation showed striking variations. In longitudinal slices, where rostrocaudal association fibers are best preserved, discharge propagation resembled in vivo seizure activity in the following respects: propagation was as rapid as in vivo and about two to three times faster than in other slices; discharges jumped abruptly between the En and PC; and discharges had large amplitudes in superficial layers of the PC. Cuts in longitudinal slices that partially separated the PC from the En eliminated these unique features. These results help clarify why epileptiform activity differs between in vitro and in vivo experiments and suggest that rostrocaudal pyramidal cell association fibers play a major role in the propagation of discharges in the intact brain. The longitudinal PC slice, which best preserves these fibers, is ideally suited for the study their role.

Animals↗
PubMed2001

Effects of maternal bilateral adrenalectomy on fetal rat cerebral cortex.

We investigated the effects of maternal bilateral adrenalectomy (ADX) on fetal rat cerebral cortices by assessing morphological and morphometrical parameters in light and electron microscopy studies. Pregnant adult rats underwent ADX on day 4 of gestation. Embryonic brain tissue from control and ADX groups were examined at each of the 10 embryonic stages, days 11 through 20 (E11-E20). Control and adrenalectomized pregnant females were sacrificed at each fetal stage, fetuses were removed from the uterine horns, and their brain tissue was processed for light and electron microscopy examination. In the ADX fetuses, the cortical laminae were thicker and overall cortex thickness was greater, but structural differentiation in the primitive cortical layers was delayed compared with that observed in controls. Apart from the differences in embryonic cell development noted at the structural level, we found no noticeable ultrastructural differences between the cerebral cortices of ADX and control fetuses at any of the stages studied. Overall, the ADX group's cortical tissue exhibited a greater degree of cell migration, an extended proliferative period in the cortical layers with the highest proportion of mitotic activity, and a greater thickness than that of control specimens. We believe that by eliminating the inhibitor effects of glucocorticoids, ADX effectively induces mitotic activity and extends the proliferative periods in developing cerebral cortex.

Adrenal Glands↗
PubMed2001

Immunohistochemical detection of CD45+, CD56+, and CD14+ cells in human decidua during early pregnancy.

The densities and distribution of innate immune system cells, NK cells and macrophages, was investigated between days 22-30 post coitus of very early pregnancy. Paraffin sections were labelled by the avidin-biotin complex-peroxidase method using monoclonal antibodies specific for CD45, CD56 and CD14. Positive cells were quantified and the results were analysed using ANOVA tests. It was found that ~40% of all cells were leukocytes and ~30% of the leukocytes were NK cells and ~22% were macrophages. The number of CD56+ cells increased as pregnancy progressed. CD56+ were observed cells close to the luminal epithelium and were especially noticeable around glands where they often occurred in small clusters. Decidual macrophages (CD14+) were distributed throughout the decidual stroma of early pregnancy and were observed in greatest numbers around the vessel walls. Their numbers have also increased as pregnancy progressed. The great abundance of these leukocytes, which are known as members of the innate immune system, in early pregnancy decidua suggests that these cells are important for fetal survival and pregnancy success. The relevance of the distribution of CD45+, CD56+ and CD14+ in decidua at the fourth week of pregnancy to the immunological barrier between mother and fetus is discussed.

Adult↗
PubMed2000

Imaging epileptiform discharges in slices of piriform cortex with voltage-sensitive fluorescent dyes.

Voltage imaging techniques were used to investigate epileptiform discharges in brain slices containing piriform cortex (PC). These experiments pinpointed the site of discharge onset in the endopiriform nucleus (En). Under some conditions, discharge onset also occurred simultaneously in adjoining neocortex. With slightly suprathreshold electrical stimulation, discharge generation was a two-stage process in which onset was preceded by a sustained spatially localized depolarization denoted as plateau activity. Plateau activity was seen away from the onset site, in a border region between En and layer III of PC. A similar two-stage sequence was seen for slices taken from a variety of planes, using two different interictal models as well as an ictal model. Plateau activity was found to be necessary for the generation of both kinds of discharge. Synaptic transmission at the site of onset was found to be required for the generation of interictal-like discharges, but ictal-like discharges were different in that they could still be generated when synaptic transmission at this site was impaired. These studies identify specialized regions with potentially important roles in epileptogenesis and help to elucidate the neuronal circuitry that can produce epileptiform activity.

Animals↗
PubMed2000

Characteristics of plateau activity during the latent period prior to epileptiform discharges in slices from rat piriform cortex.

The deep piriform region has an unusually high seizure susceptibility. Voltage imaging previously located the sites of epileptiform discharge onset in slices of rat piriform cortex and revealed the spatiotemporal pattern of development of two types of electrical activity during the latent period prior to discharge onset. A ramplike depolarization (onset activity) appears at the site of discharge onset. Onset activity is preceded by a sustained low-amplitude depolarization (plateau activity) at another site, which shows little if any overlap with the site of onset. Because synaptic blockade at either of these two sites blocks discharges, it was proposed that both forms of latent period activity are necessary for the generation of epileptiform discharges and that the onset and plateau sites work together in the amplification of electrical activity. The capacity for amplification was examined here by studying subthreshold responses in slices of piriform cortex using two different in vitro models of epilepsy. Under some conditions electrically evoked responses showed a nonlinear dependence on stimulus current, suggesting amplification by strong polysynaptic excitatory responses. The sites of plateau and onset activity were mapped for different in vitro models of epilepsy and different sites of stimulation. These experiments showed that the site of plateau activity expanded into deep layers of neighboring neocortex in parallel with expansions of the onset site into neocortex. These results provide further evidence that interactions between the sites of onset and plateau activity play an important role in the initiation of epileptiform discharges. The site of plateau activity showed little variation with different stimulation sites in the piriform cortex, but when stimulation was applied in the endopiriform nucleus (in the sites of onset of plateau activity), plateau activity had a lower amplitude and became distributed over a much wider area. These results indicate that in the initiation of epileptiform discharges, the location of the circuit that generates plateau activity is not rigidly defined but can exhibit flexibility.

Animals↗
PubMed2000

Prevalence of chronic bronchitis and associated risk factors in a rural area of Kayseri, Central Anatolia, Turkey.

This population-based cross-sectional survey was carried out to determine the prevalence of chronic bronchitis and associated risk factors in a rural area of Kayseri, Central Anatolia, Turkey. Subjects (1,023) aged 20-83 yrs (81.8% of eligible subjects) were interviewed using a modified version of the adult questionnaire compiled by the European Community Respiratory Health Survey. Subjects with "presence of cough and phlegm on most days during at least three months per year for at least the two previous years" were classified as having chronic bronchitis. According to the criteria used, 138 (13.5%) were classified as having chronic bronchitis. The prevalence was higher in males (17.8%) than females (10.0%). There was no overall significant association between chronic bronchitis and age in males, but, in females, the difference between age groups was important. There was no association between chronic bronchitis and family income, although the prevalence was highest in the low-income group. Subjects who reported childhood respiratory illnesses had a 1.7-fold increased risk of chronic bronchitis compared to those without such a history. The prevalence was much higher among people exposed to biomass fuel combustion and among smokers and exsmokers than among nonsmokers. In multivariate analyses, a significant increase in the prevalence of chronic bronchitis was seen in males, those who had received poor schooling, those reporting childhood respiratory illnesses, and those exposed to biomass fuel combustion and according to smoking habit.

Adult↗
PubMed1999

Sustained plateau activity precedes and can generate ictal-like discharges in low-Cl(-) medium in slices from rat piriform cortex.

Interictal and ictal discharges represent two different forms of abnormal brain activity associated with epilepsy. Ictal discharges closely parallel seizure activity, but depending on the form of epilepsy, interictal discharges may or may not be correlated with the frequency, severity, and location of seizures. Recent voltage-imaging studies in slices of piriform cortex indicated that interictal-like discharges are generated in a two-stage process. The first stage consists of a sustained, low-amplitude depolarization (plateau activity) lasting the entire latent period prior to discharge onset. Plateau activity takes place at a site distinct from the site of discharge onset and serves to sustain and amplify activity initiated by an electrical stimulus. In the second stage a rapidly accelerating depolarization begins at the onset site and then spreads over a wide region. Here, we asked whether ictal-like discharges can be generated in a similar two-stage process. As with interictal-like activity, the first sign of an impending ictal-like discharge is a sustained depolarization with a plateau-like time course. The rapidly accelerating depolarization that signals the start of the actual discharge develops later at a separate onset site. As found previously with interictal-like discharges, local application of kynurenic acid to the plateau site blocked ictal-like discharges throughout the entire slice. However, in marked contrast to interictal-like activity, blockade of synaptic transmission at the onset site failed to block the ictal-like discharge. This indicates that interictal- and ictal-like discharges share a common pathway in the earliest stage of their generation and that their mechanisms subsequently diverge.

Animals↗
PubMed1999

Sustained and accelerating activity at two discrete sites generate epileptiform discharges in slices of piriform cortex.

When near-threshold electrical stimulation is used to evoke epileptiform discharges in brain slices, a latent period of up to 150 msec elapses before the discharge begins. During this period most neurons are silent, and abnormal electrical activity is difficult to detect with microelectrodes. A fundamental question about epileptiform activity concerns how synchronous discharges arise abruptly in a relatively quiescent slice. This issue was addressed here by using voltage imaging techniques to study epileptiform discharges in rat piriform cortex slices. These experiments revealed two distinct forms of electrical activity during the latent period. (1) A steeply increasing depolarization, referred to here as onset activity, has been described previously and occurs at the site of discharge onset. (2) A sustained depolarization that precedes onset activity, referred to here as plateau activity, has not been described previously. Plateau and onset activity occurred in different subregions of the endopiriform nucleus (a region of high seizure susceptibility). When cobalt or kynurenic acid was applied focally to inhibit electrical activity at the site of plateau activity, discharges were blocked. However, application of these agents to other nearby sites (except the site of onset) failed to block discharges. Plateau activity represents a novel form of electrical activity that precedes and is necessary for epileptiform discharges. Discharges thus are generated in a sequential process by two spatially distinct neuronal circuits. The first circuit amplifies and sustains activity initiated by the stimulus, and the second generates the actual discharge in response to an excitatory drive from the first.

Animals↗